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ZusammenfassungDas nächtliche Einnässen im Kindesalter ist ein häufiger Konsultationsgrund im kinderurologischen Alltag. Nach heutiger Ansicht sind psychische Probleme („die Seele weint“) meistens nicht ursächlich. Die Ätiologie ist multifaktoriell inklusive einer genetischen Prädisposition und bisher nicht im Detail geklärt. Aber für viele Familien ist dies eine belastende Situation, und sie kann das Selbstwertgefühl und psychische Wohlbefinden der Kinder und Jugendlichen deutlich beeinträchtigen.Mit einer gründlichen kinderurologischen Anamnese, einem Trink- und Miktionsprotoll und körperlicher Untersuchung lassen sich kindliche Miktionsstörungen meistens gut differenzieren. Je nach Befund sind im Verlauf weitere Untersuchungen indiziert, insbesondere wenn eine organische Ursache vermutet wird. Wichtig hierbei ist, zu unterscheiden, ob es sich um eine isolierte monosymptomatische Enuresis nocturna handelt oder die Enuresis nocturna Ausdruck einer weiteren kindlichen Miktionsstörung ist (nichtmonosymptomatische Enuresis nocturna).Die Therapie richtet sich nach den möglichen Ursachen und dem Wunsch der Patienten und deren Familien. Eine monosymptomatische Enuresis nocturna hat durchaus einen sehr hohen Grad an Selbstheilungstendenz ohne Therapie oder nur mittels einfacher Verhaltensmassnahmen. Bei Therapiewunsch stehen eine medikamentöse Behandlung und/oder eine Konditionierung durch einen Weckapparat zur Verfügung.Sofern es sich um eine nichtmonosymptomatische Enuresis nocturna handelt, sind o. g. Therapien meistens frustran. Der therapeutische Ansatz hierbei ist je nach Ursache individuell und reicht von einfachen Verhaltensmassnahmen (z. B. bei Reifungsverzögerung der Blasenentwicklung) bis hin zu operativen Verfahren (z. B. bei posterioren Urethralklappen beim Knaben).

Objectives To show the feasibility of magnetic double-J-stent (mDJS) removal without general anaesthesia in infants and children. Methods A retrospective analysis of mDJS removals was conducted between February 2018 and July 2020 in a cohort of 32 consecutive paediatric patients. Only patients with unilateral ureteric stenting were included. Stent retrieval was performed in an outpatient setting. In males the junction of the retrieval-catheter and the mDJS was confirmed by transabdominal ultrasound. All patients were followed-up for 4-12 weeks after stent removal. Results Thirty-two patients (54% males) were included. Median age was 3.8 years (range 1 month - 15 years). Ureteral stents remained in place for a median of 67.5 days (range 2 days - 6 months). General anaesthesia was necessary in one single patient due to expressed patient's and caregiver's wish. Thirty-one patients had stent removal without need for general anaesthesia. Thereof, nitrous oxide was used in 12 patients (37.5%), fentanyl in 3 patients (9.4%), midazolam in 3 patients (9.4%), and 17 patients (53.1%) did not need sedation at all. Seven patients (21.9%) being 8 months or younger had received peroral saccharosis. No complications occurred during stent removal. Retrieval was successful at first catheterization in 30 patients (93.8%). Two male patients needed a second catheterization (6.3%). Conclusion The use of magnetic DJS is safe in the paediatric population and spares general anaesthesia during removal in almost all patients.

ZusammenfassungDer vesikoureterale Reflux (VUR) beschreibt einen nichtphysiologischen Reflux der Harnblase in die Nieren. Während beim primären Reflux und jüngeren Kindern eine hohe Spontanheilungsrate besteht, ist diese beim sekundären Reflux deutlich geringer. Der VUR ist häufig mit einer „bladder bowel dysfunction“ assoziiert, die primär behandelt werden sollte. Hauptkomplikation ist die Refluxnephropathie mit Bildung von Nierennarben und nachfolgend möglicher Einschränkung der Nierenfunktion. Die Therapiemöglichkeiten reichen, abhängig von der klinischen Präsentation und den bestehenden Risikofaktoren, von abwartendem Verhalten bis zur offenen Chirurgie. Ein leichtgradiger VUR (Grad I–II) muss heute nicht mehr behandelt werden. Bei hochgradigem VUR und wiederholten Durchbruchsinfektionen ist die Indikation zur subureteralen Unterspritzung oder zur Ureterneuimplantation gegeben.

Objective Hirschsprung's disease (HSCR) is a congenital intestinal neurodevelopmental disorder characterized by the absence of enteric ganglion cells in the distal colon. Although Hirschsprung-associated enterocolitis (HAEC) is the most frequent life-threatening complication in HSCR, to date reliable biomarkers predicting the likelihood of HAEC are yet to be established. We established a three-center retrospective study including 104 HSCR patients surgically treated between 1998 and 2019. Materials and Methods Patient-derived cryopreserved or paraffin-preserved colonic tissue at surgery was analyzed via βIII-tubulin immunohistochemistry. We subsequently determined extrinsic mucosal nerve fiber density in resected rectosigmoid specimens and classified HSCR patients accordingly into nerve fiber-high or fiber-low groups. We compared the distribution of clinical parameters obtained from medical records between the fiber-high (n = 36) and fiber-low (n = 68) patient groups. We assessed the association between fiber phenotype and enterocolitis using univariate and multivariate logistic regression adjusted for age at operation. Results Enterocolitis was more prevalent in patients with sparse mucosal nerve fiber innervation (fiber-low phenotype, 87%) compared with the fiber-high phenotype (13%; p = 0.002). In addition, patients developing enterocolitis had a younger age at surgery (3 vs. 7 months; p = 0.016). In the univariate analysis, the odds for enterocolitis development in the fiber-low phenotype was 5.26 (95% confidence interval [CI], 1.67–16.59; p = 0.005) and 4.01 (95% CI, 1.22–13.17; p = 0.022) when adjusted for age. Conclusion Here, we showed that HSCR patients with a low mucosal nerve fiber innervation grade in the distal aganglionic colon have a higher risk of developing HAEC. Consequently, histopathologic analysis of the nerve fiber innervation grade could serve as a novel sensitive prognostic marker associated with the development of enterocolitis in HSCR patients.

Summary Background & aims Plasma citrulline, a non-protein amino acid, is a biochemical marker of small intestine enterocyte mass in humans. Indeed, citrulline is highly correlated with residual bowel length in patients with short bowel syndrome. It is known to be synthesised in epithelial cells of the small intestine from other amino acids (precursors). Citrulline is then released into systemic circulation and interconverted into arginine in kidneys. If plasma citrulline concentration depends on abundance of intestinal amino acid transporters is not known. The aim of the present study was to explore whether plasma citrulline concentration correlates with the expression of intestinal amino acid transporters. Furthermore, we assessed if arginine in urine correlates with plasma citrulline. Methods Duodenal samples, blood plasma and urine were collected from 43 subjects undergoing routine gastroduodenoscopy. mRNA expression of seven basolateral membrane amino acid transporters/transporter subunits were assessed by real-time PCR. Plasma and urine amino acid concentrations of citrulline, its precursors and other amino acids were analysed using High Performance Liquid Chromatography measurements. Amino acid transporter mRNA expression was correlated with blood plasma and urine levels of citrulline and its precursors using Spearman's rank correlation. Likewise, urine arginine was correlated with plasma citrulline. Results Plasma citrulline correlated with the mRNA expression of basolateral amino acid transporter LAT4 (Spearman's r = 0.467, p = 0.028) in small intestine. None of the other basolateral membrane transporters/transporter subunits assessed correlated with plasma citrulline. Plasma citrulline correlated with urinary arginine, (Spearman's r = 0.419, p = 0.017), but not with urinary citrulline or other proteinogenic amino acids in the urine. Conclusions In this study, we showed for the first time that small intestinal basolateral LAT4 expression correlates with plasma citrulline concentration. This finding indicates that LAT4 has an important function in mediating citrulline efflux from enterocytes. Furthermore, urine arginine correlated with plasma citrulline, indicating arginine in the urine as possible additional marker for small intestine enterocyte mass. Finally, basolateral LAT4 expression along the human small intestine was shown for the first time.

Kinderchirurgen Donald Nuss 1998, hat die Behandlung der Trichterbrust revolutioniert. Seither hat sich diese Methode deutlich weiterentwickelt, um die Operation noch einfacher und vor allem sicherer zu machen. Demgegenüber hat sich auch die konservative Therapie weiterentwickelt und an Stellenwert gewonnen. Entsprechend soll für jeden Patienten individuell die optimale Therapie gefunden werden.

Le pectus excavatum ou thorax en entonnoir est la malformation du thorax la plus fréquente. L’opération mini-invasive du thorax en entonnoir, décrite pour la première fois par le chirurgien pédiatre américain Donald Nuss en 1998, a révolutionné le traitement de cette malformation.

Introduction Lower urinary tract symptoms (LUTS) in children are common. In 2005, Akbal et al published the dysfunctional voiding and incontinence scoring system (DVAISS) to assess patient's symptoms. Our study aimed to determine the value of this scoring system for predicting the severity and clinical course of voiding abnormalities in children and adolescents. Material and Methods Patients' symptoms were scored using the DVAISS in children and adolescents with LUTS presenting for the first time to our pediatric urology department between January 2010 and December 2015. We correlated the calculated score with voiding volume, clinical course, and outcome. Results A total of 168 patients (113 boys, 55 girls; age 5–18 years) with isolated LUTS were included. In 53 patients (group 1), the DVAISS score was less than or equal to 8.5 and in the other 115 patients (group 2), the score was greater than 8.5 suggestive for relevant voiding abnormalities. Patients in group 1 showed a significantly higher average voiding volume (200 vs. 110 mL, p = 0.001). The median time for symptom resolution was significantly higher in group 2 than group 1 (14 vs. 8 months; p = 0.018). The severity of LUTS could be determined by these parameters. Conclusion Based on the DVAISS, a prediction of the clinical course and approximate treatment duration is possible. Therefore, the DVAISS is useful to assess LUTS in children and is also a valuable tool in rating the severity of the disease. It is also a quite precise predictor of the time needed to resolve the symptoms.

L-Citrulline is a non-essential but still important amino acid that is released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become a biomarker to monitor intestinal integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins are useful to monitor rheumatoid diseases. Citrullinated histones, however, may even predict a worse outcome in cancer patients. Supplementation of citrulline is better tolerated compared to arginine and might be useful to slightly improve muscle strength or protein balance. The following article shall provide an overview of L-citrulline properties and functions, as well as the current evidence for its use as a biomarker or as a therapeutic supplement.

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential., Cells, 10 (5), ISSN:2073-4409

Objective For patients with pancreatic and peri-ampullary adenocarcinoma, it has been hypothesized that extended lymphadenectomy may result in higher R0 resection rates and improved survival. As such, the objective of this systematic review was to compare the oncologic outcomes after pancreaticoduodenectomy (PD) with standard lymphadenectomy (SLA) versus PD with extended lymphadenectomy (ELA). Methods A Cochrane systematic review was conducted to identify all randomized controlled trials comparing PD with SLA versus PD with ELA for participants with periampullary or pancreatic cancer. The following electronic databases were reviewed: the Cochrane Central Register of Controlled Trials; MEDLINE; PubMed and EMBASE. The methodological quality of the included studies was assessed using the Cochrane risk of bias criteria and the quality of evidence for important outcomes using GRADE. Extended lymphadenectomy included the interaortocaval space, left side of the celiac trunk, and superior mesenteric artery. Results Seven randomized controlled trials were included with 843 patients (421 ELA and 422 SLA). No difference in overall survival (1- and 3-years after surgery) was seen between groups. Mortality and morbidity rates (including pancreatic fistula, delayed gastric emptying, and postoperative bleeding) were similar between the two groups. Operative time was significantly longer following extended resection (Mean Difference 50.1 min; 95% CI 19.2 to 81.1 min; P = 0.001). Total amount of blood loss during surgery was significantly increased following extended resection (Mean Difference 137 ml; 95% CI 12 to 263 ml; P = 0.03), as well as transfusion requirements (Mean Difference 0.15 units; 95% CI 0.13 to 0.17 units; P More lymph nodes were retrieved during ELA (Mean Difference 11 nodes; 95% CI 7 to 15 nodes; P Conclusion There is no indication for extended lymphadenectomy in pancreatic head resection as a routine procedure.

Testicular torsion is a surgical emergency. Early diagnosis and surgical treatment are vital in order to preserve the affected gonad. Current surgical teaching emphasizes sudden, severe, persistent, unilateral scrotal pain as a cardinal symptom of testicular torsion. We present the case of unilateral testicular torsion in a 14-year-old patient who presented with the absence of severe pain. Despite a delayed presentation to the emergency department, the gonad could be salvaged successfully. Literature on the topic of testicular torsion presenting with minimal pain is limited. Nevertheless, pediatric surgeons might be faced with cases similar to the one we describe. Underestimating this phenomenon might lead to a delay of treatment. In such cases, ultrasound can be a beneficial addition in the diagnosis and accelerate definitive operative treatment. The presented case clearly demonstrates that, although we do not include testicular torsion without severe pain in our surgical teaching algorithms, we might encounter it in our clinical practice.

Gastroschisis and omphalocele reflect the two most common abdominal wall defects in newborns. First postnatal care consists of defect coverage, avoidance of fluid and heat loss, fluid administration and gastric decompression. Definitive treatment is achieved by defect reduction and abdominal wall closure. Different techniques and timings are used depending on type and size of defect, the abdominal domain and comorbidities of the child. The present review aims to provide an overview of current treatments.

The coincidence of two rare diseases such as congenital diaphragmatic hernia (CDH) and neuroblastoma is exceptional. With an incidence of around 2–3:10,000 and 1:8000 for either disease occurring on its own, the chance of simultaneous presentation of both pathologies at birth is extremely low. Unfortunately, the underlying processes leading to congenital malformation and neonatal tumors are not yet thoroughly understood. There are several hypotheses revolving around the formation of CDH and neuroblastoma. The aim of our study was to put the respective hypotheses of disease formation as well as known factors in this process into perspective regarding their similarities and possible overlaps of congenital disease formation. We present the joint occurrence of these two rare diseases based on a patient presentation and immunochemical prognostic marker evaluation. The aim of this manuscript is to elucidate possible similarities in the pathogeneses of both disease entities. Discussed are the role of toxins, cell differentiation, the influence of retinoic acid and NMYC as well as of hypoxia. The detailed discussion reveals that some of the proposed pathophysiological mechanisms of both malformations have common aspects. Especially disturbances of the retinoic acid pathway and NMYC expression can influence and disrupt cell differentiation in either disease. Due to the rarity of both diseases, interdisciplinary efforts and multi-center studies are needed to investigate the reasons for congenital malformations and their interlinkage with neonatal tumor disease.

Background & AimsHirschsprung’s disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric nervous cells (ganglia). The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates extramural innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown.MethodsWe enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal cholinergic innervation using immunohistochemistry. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using quantitative reverse-transcribed real-time polymerase chain reaction (qRT-PCR) of whole colonic tissue and fluorescence-activated cell sorting (FACS) analysis of isolated colonic immune cells. Fiber-associated immune cells were identified using confocal immunofluorescence microscopy and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic patient tissue using 16S rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation.ResultsWe provided evidence that extrinsic mucosal innervation correlated with reduced interleukin (IL)-17 cytokine levels and T-helper-17 (Th17) cell frequencies. Bipolar CD14high macrophages colocalized with neurons and expressed significantly less interleukin-23, a Th17-promoting cytokine. HSCR patients lacking mucosal cholinergic nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis.ConclusionThe mucosal fiber phenotype might serve as a new prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new future therapeutic options. (www.clinicaltrials.gov accessing number NCT03617640)

Ziel der randomisierten kontrollierten klinischen Studie war es herauszufinden, ob die Behandlung kindlicher Claviculafrakturen mit einem Rucksackverband vergleichbare Ergebnisse erzielt (bezogen auf Schulterfunktion, Schmerz und Zufriedenheit) als ohne jegliche Ruhigstellung. Hierfur wurden 2 Studienarme gebildet, bei denen die Kinder altersabhangig (Ein- bis 4‑ und 5‑ bis 12-Jahrige) entweder der Gruppe mit Rucksackverband oder der Gruppe „Beobachtung“ zugeteilt wurden. In den Ergebnissen zeigte sich, dass es keine Unterschiede in der Schulterfunktion nach 6 Monaten zwischen den beiden Studienarmen sowie keine Unterschiede zwischen den beiden Studienarmen in beiden Altersgruppen gab. Die Schmerzintensitat zeigte keinen signifikanten Unterschied bei Kindern im Alter von einem bis 4 Jahre nach 5 Tagen und nach 3 Wochen; nach 6 Monaten wurden in beiden Gruppen keine Schmerzen angegeben. Bei Kindern im Alter von 5 bis 12 Jahren zeigte sich kein Unterschied nach 5 Tagen; nach 3 Wochen und nach 6 Monaten wurden in beiden Gruppen keine Schmerzen angegeben. Bei der Zufriedenheit der Eltern in Bezug auf die Behandlung zeigte sich bei den Eltern am Tag 5 eine hohere Zufriedenheit in der Gruppe ohne Rucksackverband; kein Unterschied bestand nach 6 Wochen oder nach 6 Monaten. Fazit: Somit kann man postulieren, dass das Tragen eines Rucksackverbands nach kindlicher Claviculafraktur in Bezug auf Schulterfunktion, Schmerzintensitat und Zufriedenheit nach 6 Monaten keine Vorteile bietet. Detaillierter betrachtet mag eine Ruhigstellung bei den Ein- bis 4‑Jahrigen sogar mehr Nachteile mit sich bringen (Angehorigenzufriedenheit ist hier an Tag 5 ohne Verband hoher), bei den 5‑ bis 12-Jahrigen hingegen eine analgetische Komponente besitzen (Schmerzmittelverbrauch an Tag 5 hoher bei gleicher Schmerzintensitat).

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.

[Abstract] Hirschsprung disease (HSCR, OMIM 142623) involves congenital intestinal obstruction caused by dysfunction of neural crest cells and their progeny during enteric nervous system (ENS) development. HSCR is a multifactorial disorder; pathogenetic variants accounting for disease phenotype are identified only in a minority of cases, and the identification of novel disease-relevant genes remains challenging. In order to identify and to validate a potential disease-causing relevance of novel HSCR candidate genes, we established a complementary study approach, combining whole exome sequencing (WES) with transcriptome analysis of murine embryonic ENS-related tissues, literature and database searches, in silico network analyses, and functional readouts using candidate gene-specific genome-edited cell clones. WES datasets of two patients with HSCR and their non-affected parents were analysed, and four novel HSCR candidate genes could be identified: ATP7A, SREBF1, ABCD1 and PIAS2. Further rare variants in these genes were identified in additional HSCR patients, suggesting disease relevance. Transcriptomics revealed that these genes are expressed in embryonic and fetal gastrointestinal tissues. Knockout of these genes in neuronal cells demonstrated impaired cell differentiation, proliferation and/or survival. Our approach identified and validated candidate HSCR genes and provided further insight into the underlying pathomechanisms of HSCR., [Author summary] Hirschsprung disease (HSCR) is a rare developmental disorder. It leads to the absence of enteric nerve cells (aganglionosis) in the large intestine and is caused by functional defects of neuronal precursor cells during embryonic development of the gut nervous system. The aganglionosis manifests as a variety of symptoms including impaired peristalsis and the formation of a pathogenic dilatation of the intestine (megacolon). The etiology of HSCR is considered to be multifactorial. Variants in more than 20 genes have been reported to be overrepresented in HSCR and replicated in independent cohorts. However, variants in those risk genes account for only 30% of all cases, suggesting that many more genes have to be implicated in the development of HSCR. As the identification and the subsequent validation of novel gene variants to be disease-causing or not, still remains a major challenge, we established and applied a complementary study pipeline. This enabled us to identify four novel candidate genes in two HSCR patients and to validate their potential disease relevance. Our approach represents a suitable way to dissect the complex genetic architecture underlying HSCR., This study was supported by the Heidelberg Stiftung Chirurgie (https://www.stiftung-chirurgie.de) (P. Romero and B. Niesler), the Heinz and Heide Dürr Stiftung (https://www.heinzundheideduerrstiftung.de) (B. Niesler and P. Romero; 2017/2.2.1/04), the Heidelberg University Hospital (https://www.heidelberg-university-hospital.com) (G. Rappold), and the Dres. Majic/Majic Schlez Stiftung (T. Mederer). Tanja Mederer is a PhD fellow of HBIGS (http://www.hbigs.uni-heidelberg.de) and was funded by the Studienstiftung des Deutschen Volkes (https://www.studienstiftung.de). Cristina Martínez is supported by Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Ciencia, Innovación y Universidades (https://www.isciii.es) (CP18/00116). Salud Borrego was supported by Instituto de Salud Carlos III (https://www.isciii.es) through the project "PI16/0142" and "PI19/01550" (Co-funded by European Regional Development Fund/European Social Fund "A way to make Europe"/"Investing in your future").

Background: multisystem inflammatory syndrome in children (MIS-C) is a new disease associated with a recent infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Affected children can present predominantly with abdominal symptoms, fever and high inflammatory parameters that might lead to a consult by the pediatric surgeon and an indication for surgery. Methods: clinical data of three patients with MIS-C that underwent surgery were collected. Histopathological analysis of the appendix was performed. Results: we present the clinical course of three children with fever, abdominal pain and vomiting for several days. Clinical examination and highly elevated inflammation markers led to indication for laparoscopy, appendectomy was performed in two patients. Because of intraoperative findings or due to lack of postoperative improvement, all patients were reevaluated and tested positive for MIS-C associated laboratory parameters and were subsequently treated with corticosteroids, intravenous immunoglobulins, acetyl salicylic acid and/or light molecular weight heparin. Conclusions: we discuss the implications of MIS-C as a new differential diagnosis and stress the importance of assessing the previous medical history, identifying patterns of symptoms and critically surveilling the clinical course. We implemented an algorithm for pediatric surgeons to consider MIS-C as a differential diagnosis for acute abdomen that can be integrated into the surgical workflow.

Acute appendicitis is the most common indication for pediatric abdominal emergency surgery. Determination of the severity of appendicitis on clinical grounds is challenging. Complicated appendicitis presenting with perforation, abscess or diffuse peritonitis is not uncommon. The question remains why and when acute appendicitis progresses to perforation. The aim of this study was to assess the impact of water permeability on the severity of appendicitis. We show that AQP1 expression and water permeability in appendicitis correlate with the stage of inflammation and systemic infection parameters, leading eventually to perforation of the appendix. AQP1 is also expressed within the ganglia of the enteric nervous system and ganglia count increases with inflammation. Severity of appendicitis can be correlated with water permeability measured by AQP1 protein expression and increase of ganglia count in a progressive manner. This introduces the question if regulation of water permeability can present novel curative or ameliorating therapeutic options.

PURPOSE: The prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants

Background The enteric nervous system (ENS), a complex network of neurons and glial cells, coordinates major gastrointestinal functions. Impaired development or secondary aberrations cause severe enteric neuropathies. Neural crest-derived stem cells as well as enteric neuronal progenitor cells, which form enteric neurospheres, represent a promising tool to unravel molecular pathomechanisms and to develop novel therapy options. However, so far little is known about the detailed cellular composition and the proportional distribution of enteric neurospheres. Comprehensive knowledge will not only be essential for basic research but also for prospective cell replacement therapies to restore or to improve enteric neuronal dysfunction. Methods Human enteric neurospheres were generated from three individuals with varying age. For detailed molecular characterization, nCounter target gene expression analyses focusing on stem, progenitor, neuronal, glial, muscular, and epithelial cell markers were performed. Corresponding archived paraffin-embedded individuals' specimens were analyzed accordingly. Key results Our data revealed a remarkable molecular complexity of enteric neurospheres and archived specimens. Amongst the expression of multipotent stem cell, progenitor cell, neuronal, glial, muscle and epithelial cell markers, moderate levels for the pluripotency marker POU5F1 were observed. Furthermore, besides the interindividual variability, we identified highly distinct intraindividual expression profiles. Conclusions & inferences Our results emphasize the assessment of molecular signatures to be essential for standardized use, optimization of experimental approaches, and elimination of potential risk factors, as the formation of tumors. Our study pipeline may serve as a blueprint implemented into the characterization procedure of enteric neurospheres for various future applications.

Objectives In newborn rodents, intestinal maturation involves delayed fructose transporter GLUT5 expression until weaning. In jejunoileal atresia (JIA), distal intestinal segments lack exposure to amniotic fluid-containing carbohydrates. We assessed in human newborns, the impact of intestinal maturation and obstruction on mucosal monosaccharide transporter expression. Methods Samples were obtained from 10 newborns operated for small intestinal atresia and from 17 adults undergoing gastroduodenoscopy and/or ileocolonoscopy. mRNA expression of the transporters SGLT1, GLUT1, GLUT2, GLUT5, and GLUT7 was measured in neonate samples proximal and distal of the atresia as well as in adult duodenum, ileum, and colon. Protein expression and localization was assessed using immunofluorescence. Results Although mRNA expression of monosaccharide transporters did not significantly differ between newborn and adult samples, luminal fructose transporter GLUT5 protein was absent in 0- to 4-day-old neonates, but expressed in adults. The mRNA expression of the 5 tested monosaccharide transporters was unchanged distal from the JIA relative to proximal. Similarly, luminal sodium-dependent glucose transporter SGLT1 and basolateral GLUT2 were expressed proximal and distal to JIA as visualized by immunofluorescence staining. With the exception of glucose transporter GLUT1 that showed highest expression levels in colon, all investigated hexose transporters showed strongest expression in duodenum, lower levels in ileum and lowest in colon. Conclusions Human newborns lack small intestinal fructose transporter GLUT5 protein expression and small intestinal atresia does not affect the expression of hexose transporters.

Rationale: Damage control is a staged surgical approach to manage polytraumatized patients. The damage control approach comprises three steps. First, bleeding is controlled and fractures are stabilized temporarily; second, vital parameters are stabilized and the child is rewarmed in the intensive care unit; and third, the child is reoperated for definitive repair of injuries. We aimed to describe the feasibility of the damage control orthopedic approach in a child. Patient concerns: An 8-year-old girl fell from the balcony of the 5th floor onto concrete pavement and was admitted to our accident and emergency ward in a stable cardiorespiratory state, but with gross deformity of the lower limbs, left thigh, and forearm. Diagnoses: The child had sustained multiple injuries with severe bilateral lung contusion, pneumothorax, fracture of first rib, liver laceration, stable spine fractures, transforaminal fracture of sacrum, pelvic ring fracture, displaced baso-cervical femoral neck fracture, displaced bilateral multifragmental growth plate fractures of both tibiae, fractures of both fibulae, displaced fracture of left forearm, and displaced supracondylar fracture of the humerus. Intervention: In the initial operation, we performed closed reduction and K-wire fixation of the right tibia, closed reduction and external fixation of the left tibia, open reduction and screw osteosynthesis of the femoral neck fracture, closed reduction and K-wire fixation of the radius, and closed reduction of the supracondylar fracture. Subsequently, we transferred the girl to the pediatric intensive care unit for hemodynamic stabilization, respiratory therapy, rewarming, and treatment of crush syndrome. In a third step, 10 days after the injury, we managed the supracondylar fracture of the humerus by closed reduction and K-wire fixation. Outcomes: Growth arrest of the left distal tibial growth plate and osteonecrosis of the femoral head and neck, slipped capital femoris epiphysis (SCFE), and coxa vara of the right femur led to balanced leg length inequality 2 years after the injury. The lesion of the left sciatic nerve improved over time and the girl walked without walking aids and took part in school sports but avoided jumping exercises. Lessons: We emphasize the importance of damage control principles when managing polytraumatized children.

We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment.

Background Several nonoperative treatments are currently available for the correction of pectus carinatum (PC). Objective The objective of this study is to report our single center experience with the dynamic compression system (DCS). Materials and Methods The DCS is a rigid aluminum brace. PC is reshaped into a normal appearance through anterior-posterior pressure and lateral expansion of the chest. Patients with chondrogladiolar PC were considered suitable for the nonoperative treatment with DCS. Results In this study, 53 of 68 children (78%) with chondrogladiolar PC were assessed retrospectively: 2 children were corrected by surgery, 12/53 (23%) treated by a conventional orthesis, 11/53 (21%) remained without therapy because of minor PC, and 36/53 (68%) were treated using the DCS. Of these 36 patients, 17 (47%) are already cured with a good (7/17) to excellent (10/17) cosmetic result after a median treatment period of 9 months (range, 2.5-16 months). The mean daily time of wearing of the device for those 17 patients was 9 hours (range, 5-18). None abandoned the treatment and there were almost no complications. Conclusions Lateral expansion of the chest and the possibility to measure the applied pressure seemed to be the key to DCSs success. We propose the DCS as first choice in the treatment of chondrogladiolar PC in children.

Rationale Acute compartment syndrome (ACS) is a feared complication following traumatic injuries. We describe the occurrence of silent ACS of the hand in a 2-year old patient with atypical symptoms. Patient concerns Our patient experienced massive swelling but minimal pain of the hand after a heavy bistro table with a stone tabletop had fallen on the right hand. Diagnosis After monitoring the development of ACS for 1 night, we noted increased firmness of the swelling and impaired perfusion of the skin covering the palm and dorsum of the hand. Notably, the patient held the hand in an intrinsic minus position but did not complain of pain after administration of only a single (weight-matched) dose of ibuprofen. Our suspicion of ACS was confirmed intraoperatively because of the elevated intramuscular pressure (up to 60 mm Hg) in several hand compartments. Interventions We performed surgical fasciotomy of all hand compartments, followed by temporary coverage of the wounds with Epigard synthetic skin substitute. The wounds were closed stepwise after 2 and 7 days, and occupational therapy was initiated after 3 weeks. Outcomes At the 1-year follow-up, we noted unrestricted wrist and finger functions of the patient. The parents reported that there was no difference in the use of the 2 hands during daily activities. Lessons The possible development of ACS should be borne in mind even in the absence of marked pain. Although the 3 A's (i.e., anxiety, agitation, and increased analgesic requirements) in the diagnosis of ACS in children are well established, some patients may experience only minimal pain. This challenges the correct and timely diagnosis of ACS in children, particularly if they are very young.