Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life.

Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+CD4+CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4+ Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-α-producing CD4+ T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth.

Revisiting Neuroblastoma: Nrf2, NF-κB and Phox2B as a Promising Network in Neuroblastoma.

Neuroblastoma is the most common solid extracranial tumor during childhood; it displays extraordinary heterogeneous clinical courses, from spontaneous regression to poor outcome in high-risk patients due to aggressive growth, metastasizing, and treatment resistance. Therefore, the identification and detailed analysis of promising tumorigenic molecular mechanisms are inevitable. This review highlights the abnormal regulation of NF-κB, Nrf2, and Phox2B as well as their interactions among each other in neuroblastoma. NF-κB and Nrf2 play a key role in antioxidant responses, anti-inflammatory regulation and tumor chemoresistance. Recent studies revealed a regulation of NF-κB by means of the Nrf2/antioxidant response element (ARE) system. On the other hand, Phox2B contributes to the differentiation of immature sympathetic nervous system stem cells: this transcription factor regulates the expression of RET, thereby facilitating cell survival and proliferation. As observed in other tumors, we presume striking interactions between NF-κB, Nrf2, and Phox2B, which might constitute an important crosstalk triangle, whose decompensation may trigger a more aggressive phenotype. Consequently, these transcription factors could be a promising target for novel therapeutic approaches and hence, further investigation on their regulation in neuroblastoma shall be reinforced.

The Dual Role of Neutrophil Extracellular Traps (NETs) in Sepsis and Ischemia-Reperfusion Injury: Comparative Analysis across Murine Models.

A better understanding of the function of neutrophil extracellular traps (NETs) may facilitate the development of interventions for sepsis. The study aims to investigate the formation and degradation of NETs in three murine sepsis models and to analyze the production of reactive oxygen species (ROS) during NET formation. Murine sepsis was induced by midgut volvulus (720° for 15 min), cecal ligation and puncture (CLP), or the application of lipopolysaccharide (LPS) (10 mg/kg body weight i.p.). NET formation and degradation was modulated using mice that were genetically deficient for peptidyl arginine deiminase-4 (PAD4-KO) or DNase1 and 1L3 (DNase1/1L3-DKO). After 48 h, mice were killed. Plasma levels of circulating free DNA (cfDNA) and neutrophil elastase (NE) were quantified to assess NET formation and degradation. Plasma deoxyribonuclease1 (DNase1) protein levels, as well as tissue malondialdehyde (MDA) activity and glutathione peroxidase (GPx) activity, were quantified. DNase1 and DNase1L3 in liver, intestine, spleen, and lung tissues were assessed. The applied sepsis models resulted in a simultaneous increase in NET formation and oxidative stress. NET formation and survival differed in the three models. In contrast to LPS and Volvulus, CLP-induced sepsis showed a decreased and increased 48 h survival in PAD4-KO and DNase1/1L3-DKO mice, when compared to WT mice, respectively. PAD4-KO mice showed decreased formation of NETs and ROS, while DNase1/1L3-DKO mice with impaired NET degradation accumulated ROS and chronicled the septic state. The findings indicate a dual role for NET formation and degradation in sepsis and ischemia-reperfusion (I/R) injury: NETs seem to exhibit a protective capacity in certain sepsis paradigms (CLP model), whereas, collectively, they seem to contribute adversely to scenarios where sepsis is combined with ischemia-reperfusion (volvulus).

Surgical Experience Affects the Outcome of Central Venous Access Catheter Implantation in Children: A Retrospective Cohort Study.

INTRODUCTION: Surgical complications occur in up to third of children, limiting the benefits of tunneled central venous catheters (tCVCs) in children. We aimed to identify risk factors for complications related to catheter implantation. METHODS: All children and adolescents undergoing tCVC implantation at a single center over a period of 9 years were analyzed. Infection, thrombosis, dislocation, and catheter dysfunction were defined as complications. Both patient-related (ie, age, sex, vessel characteristics, revision surgery) and surgical factors (ie, sex of surgeon, surgical experience) were analyzed for their association with complications. RESULTS: A total of 1024 catheters were inserted, 887 ports and 137 broviac catheters. In terms of patient-related factors, Broviac catheters, and nononcological patients had a higher complication rate. The use of the internal jugular vein and revision surgery was associated with significantly increased complications in patients with port catheters. Experience of the surgeon correlated with various outcome parameters. Implantation performed by an attending were associated with lower complication rates in comparison to those performed by residents. Within the resident group, insertions performed by experienced residents had more complications compared with those performed by residents during their first years. CONCLUSION: The study suggests that the outcome of tCVCs insertion is affected by the type of catheter used, the utilized vessel and above all by surgical experience. Residents had significantly increased complication rates in comparison to board-certified surgeons and amongst resident's outcome got worse with increasing experience of the residents. The presence of an experienced attending did not compensate for this effect. To improve the outcome of tCVCs, strategies like direct feedback after every procedure to achieve proficiency should be implanted in residency programs.

Clinical outcome, quality of life, and mental health in long-gap esophageal atresia: comparison of gastric sleeve pull-up and delayed primary anastomosis.

INTRODUCTION: Pediatric surgeons have yet to reach a consensus whether a gastric sleeve pull-up or delayed primary anastomosis for the treatment of esophageal atresia (EA), especially of the long-gap type (LGEA) should be performed. Thus, the aim of this study was to evaluate clinical outcome, quality of life (QoL), and mental health of patients with EA and their parents. METHODS: Clinical outcomes of all children treated with EA from 2007 to 2021 were collected and parents of affected children were asked to participate in questionnaires regarding their Quality of Life (QoL) and their child's Health-Related Quality of Life (HRQoL), as well as mental health. RESULTS: A total of 98 EA patients were included in the study. For analysis, the cohort was divided into two groups: (1) primary versus (2) secondary anastomosis, while the secondary anastomosis group was subdivided into (a) delayed primary anastomosis and (b) gastric sleeve pull-up and compared with each other. When comparing the secondary anastomosis group, significant differences were found between the delayed primary anastomosis and gastric sleeve pull-up group; the duration of anesthesia during anastomosis surgery (478.54 vs 328.82 min, p < 0.001), endoscopic dilatation rate (100% vs 69%, p = 0.03), cumulative time spent in intensive care (42.31 vs 94.75 days, p = 0.03) and the mortality rate (0% vs 31%, p = 0.03). HRQoL and mental health did not differ between any of the groups. CONCLUSION: Delayed primary anastomosis or gastric sleeve pull-up appear to be similar in patients with long-gap esophageal atresia in many key aspects like leakage rate, strictures, re-fistula, tracheomalacia, recurrent infections, thrive or reflux. Moreover, HrQoL was comparable in patients with (a) gastric sleeve pull-up and (b) delayed primary anastomosis. Future studies should focus on the long-term results of either preservation or replacement of the esophagus in children.

Generalized Infantile Myofibromatosis with Extensive Small Bowel Involvement in a Neonate.

Infantile myofibromatosis is a rare benign congenital tumour that often regresses spontaneously but may pose therapeutic challenges in its widespread visceral form. We present the case of a full-term neonate with generalized infantile myofibromatosis including ubiquitous subcutaneous and muscular nodules, a tumour in the mastoid and disseminated intestinal involvement. The intestinal tumours led to a mechanical ileus with intestinal perforation within the first days of life. After partial small bowel resection and necessary proximal jejunostomy the boy was dependent on total parenteral nutrition. Chemotherapy with vinblastine and methotrexate was started and was temporarily supplemented with imatinib. Feeding stayed impossible despite tumour shrinkage. At the age of 4.5 months, restoration of intestinal continuity with further stricturoplasties was performed which - for the first time - allowed complete oral feeding. Chemotherapy was continued for further two months. Currently, the child is in good general condition with growth and further disease regression. This report suggests that massive visceral involvement of infantile myofibromatosis may require extensive intestinal surgery, as conservative therapy cannot resolve the disease and its sequelae.

[Impact and Temporal Evolution of the Corona Pandemic on Pediatric Emergency Care]. / Auswirkungen der Corona Pandemie auf die Notfallversorgung im Kindesalter und die zeitliche Entwicklung im Verlauf der Pandemie.

HINTERGRUND: Die COVID-19 Pandemie hat zu massiven gesellschaftlichen und wirtschaftlichen Einschränkungen geführt. Im Kindesalter wurden elektive Vorsorgeuntersuchung oftmals nicht wahrgenommen und es zeigte sich eine Reduktion der Zahl der Notfallvorstellungen. MATERIAL UND METHODEN: In einer retrospektiven Studie erfolgte eine quantitative Auswertung aller Notfallpatienten der 5 Kindernotaufnahmen Hamburgs und der Kinder- und Jugendarztpraxen der Jahre 2019 und 2020. Zusätzlich erfolgte die detaillierte Analyse der Notfallbehandlungen des Altonaer Kinderkrankenhauses während der ersten Phase der Pandemie im Vergleich zum Vorjahr. Zusammenhänge zu den Eckpunkten der Pandemieentwicklung wurden analysiert. Die Berechnung signifikanter Unterschiede in Bezug auf die demographischen Daten und Krankheitsbilder erfolgte mittels Chi- Quadrat und t-Test. ERGEBNISSE: In allen 5 pädiatrischen Notaufnahmen Hamburgs zeigte sich eine nahezu gleichförmige Abnahme der Patientenvorstellungen während der Pandemie, ähnlich in den Kinder- und Jugendarztpraxen. Die Zahl der Behandlungen verhielt sich dabei nicht streng gegenläufig zu den Neuinfektionen, sondern korreliert eher mit den Mobilitätsdaten und entsprach somit den gesamtgesellschaftlichen Veränderungen. Während der Pandemie stieg der Anteil häuslicher Unfälle an der Gesamtzahl der Vorstellungen signifikant an. Die Analyse der Diagnosen zeigte unter anderem eine relative Abnahme von (viralen) Infektionskrankheiten. Nicht behandlungspflichtige Erkrankungen führten in der Pandemie seltener zur Vorstellung. Diese Phänomene entlasteten einerseits die Notaufnahmen, bergen aber auch die Gefahr, dass Erkrankungen durch Eltern falsch eingeschätzt werden und eine notwendige ärztliche Vorstellung somit zu spät erfolgt.

High prevalence of multidrug-resistant Gram-negative bacteria carriage in children screened prospectively for multidrug resistant organisms at admission to a paediatric hospital, Hamburg, Germany, September 2018 to May 2019.

BackgroundIncreasing resistance to antibiotics poses medical challenges worldwide. Prospective data on carriage prevalence of multidrug resistant organisms (MDRO) in children at hospital admission are limited and associated risk factors are poorly defined.AimTo determine prevalence of MDRO carriage in children at admission to our paediatric hospital in Hamburg and to identify MDRO carriage risk factors.MethodsWe prospectively obtained and cultured nasal/throat and inguinal/anal swabs from children (≤ 18 years) at admission between September 2018 and May 2019 to determine prevalence of meticillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Gram-negative bacteria (MRGN) and vancomycin-resistant enterococcus (VRE) and associated species. We collected medical histories using a questionnaire and evaluated 31 risk factors using logistic regression models.ResultsMDRO carriage prevalence of 3,964 children was 4.31% (95% confidence interval (CI): 3.69-5.00). MRSA carriage prevalence was 0.68% (95% CI: 0.44-0.99), MRGN prevalence was 3.64% (95% CI: 3.07-4.28) and VRE prevalence 0.08% (95% CI: 0.02-0.22). MDRO carriage was associated with MRGN history (odds ratio (OR): 6.53; 95% CI: 2.58-16.13), chronic condition requiring permanent care (OR: 2.67; 95% CI: 1.07-6.13), antibiotic therapy (OR: 1.92, 95% CI: 1.24-2.94), living in a care facility (OR: 3.34; 95% CI: 0.72-12.44) and refugee status in previous 12 months (OR: 1.91; 95% CI: 0.27-8.02). Compared to established practice, screening using risk-factors had better diagnostic sensitivity (86.13%; 95% CI: 80.89-91.40) and specificity (73.54%; 95% CI: 72.12-74.97).ConclusionMRGN carriage was higher than MRSA and VRE. Extended risk-factor-based admission screening system seems warranted.

Should the processus vaginalis sac be opened or closed in pediatric herniotomy? A two-center cohort study.

BACKGROUND: Inguinal hernia repair is one of the most common operations in children. To improve outcome, several techniques are used. However, it has not been established if the open or the closed hernia sac preparation technique is superior in (premature) neonates and older children. METHODS: Retrospective study including all cases of inguinal hernia repair in children at two large centers. Demographic data and outcome parameters including procedure time and intra as well as postoperative complications were evaluated. To compare open vs. closed hernia sack preparation, cases with secondary open preparation were excluded and propensity score matching was performed. Regression analysis was used to determine factors affecting operative time and recurrence rate. RESULTS: In total 2476 cases of inguinal hernia repair were identified. After exclusion of direct hernias as well as revision cases, 2257 cases were analyzed. Overall mean operative time was 25.8 min. Intraoperative complications occurred in 0.1% and. postoperative complications occurred in 3.0% of all cases, the most frequent postoperative complication being recurrence (1.7%). Closed preparation technique resulted in significantly faster procedure time and lower recurrence rates in premature neonates and older children compared to the open hernia sac preparation technique. Operative technique, prematurity, gender and training of the surgeon are highly associated with operative time, whereas operative technique is the main factor affecting recurrence rate. CONCLUSIONS: It appears that closed hernia sack preparation is superior to open regarding speed and recurrence. This was true for premature neonates, neonates and older children. All other outcome parameters including intra- and postoperative complications were similar. Thus, we recommend to use the closed preparation technique whenever possible.

Digestive enzyme expression in the large intestine of children with short bowel syndrome in a late stage of adaptation.

BACKGROUND AND AIMS: Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBS patients. METHOD: Sucrase-isomaltase (SI), lactase-phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBS patients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen. RESULTS: We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBS patients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki-67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBS patients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases. CONCLUSION: In SBS patients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre- or probiotics might offer better therapeutic approaches.

Fetoscopic techniques for prenatal covering of gastroschisis in an ovine model are technically demanding and do not lead to permanent anchoring on the fetus until the end of gestation.

INTRODUCTION: This is the cumulative technical report on the operative procedures and limitations of fetoscopic bag insertion, intestinal bag placement, and bag fixation to the fetus in a series of pilot studies in an ovine model for prenatal treatment of gastroschisis. MATERIAL AND METHODS: In 24 German blackhead sheep, a surgically created gastroschisis was managed by fetoscopic placement of the extruded intestines into a bag. The bag was then fastened onto the fetal abdominal wall. Different materials (sterile gloves, latex condoms, laparosopic retrieval bags) and different fixation techniques (laparoscopic staplers, interrupted and continuous sutures) have been examined. The fetuses were retrieved and evaluated at the end of gestation. RESULTS: Uterine bag insertion was successful in 15 of 24 (62.5%) and intestinal bag placement in 10 of 15 available fetuses (66.6%). The main factor limiting fetoscopic procedures was chorioamniotic separation (CAS). Sterilized condoms provided the most appropriate type of bags and the V-Loc™ running suture, the most expedient type of fixation, which was achieved in 9 of the 10 fetuses (complete = 2, partially = 7) by using a three port access (5 mm and 2 × 3 mm). All bags were encountered completely or partially dislocated from the fetus at the end of gestation. CONCLUSIONS: Fetoscopic intestinal bag placement and fixation in gastroschisis technically demanding. None of the evaluated techniques led to permanent anchorage of the bag to the fetus. The development of specially designed instruments, bags and fixation methods is required to optimize this approach.

Hirschsprung Disease - Clinical Relevance of RET Mutations.

Introduction To date, several genes involved in the pathogenesis of HD have been recognized. Out of these, the RET gene (chromosomal locus 10q11), one of the first genes identified in combination with HD, is still considered the basis for HD development. However, even with over a hundred RET gen coding sequence mutations identified, the mutations do not fully explain the observed sex bias of HD and the elevated risk of developing HD among siblings. Thus, our aim was to evaluate the clinical relevance of an as yet undescribed genotype in a family with HD to improve genetic counseling for families with RET mutation-associated HD.Patients This case report provides an overview of a family with a history of HD with a novel, unreported autosomal dominant RET mutation.Results/Summary The family examined in this study clearly demonstrates that (1) the genotype to phenotype correlation of patients with RET mutation-associated HD is not directly related, and (2) genetic mechanisms underlying the different HD phenotypes, as well as the model of inheritance of HD, are complex and not yet fully understood. As such, a multifactorial genesis of HD appears more likely and should be the center of genetic counseling for concerned families. Having identified another RET mutation with a possible correlation of severity of HD and gender will aid in filling the gaps of the incomplete picture of the pathogenesis of HD.Beim Morbus Hirschsprung handelt es sich um eine angeborene Aganglionose des Darms mit multifaktorieller Vererbung. Das RET-Protoonkogen (chromosomaler Locus 10q11), eines der ersten Gene, die in Kombination mit Morbus Hirschsprung identifiziert wurden, spielt dabei eine zentrale Rolle. Es wurden bereits über hundert Mutationen der RET-Gen-Codierungssequenz beschrieben. Vollständig verstanden ist jedoch weder das Wiederholungsrisiko noch die geschlechtsspezifische Ausprägung des Phänotyps. Vorgestellt wird eine Familie mit einer familiären Form eines Morbus Hirschsprung. Alle betroffenen Familienmitglieder weisen eine heterozygote Deletion c.1384_1410del (p.Ser462_THr470del) einer bisher in der Literatur noch nicht beschriebenen autosomal dominanten RET-Mutation auf. Die männlichen Betroffenen zeigen phänotypisch einen langstreckigen Morbus Hirschsprung, wohingegen bei den weiblichen betroffenen Familienmitgliedern lediglich das Rektosigmoid von der Aganglionose betroffen ist. Die untersuchte Familie ist ein erneuter Beweis für (1) die geringe Genotyp-Phänotyp-Korrelation von Patienten mit RET-assoziiertem Morbus Hirschsprung und (2) die komplexen genetischen Mechanismen, die dem Ausprägungsgrad von Morbus Hirschsprung zugrunde liegen.

Time- and dose-dependent inhibition of neutrophil extracellular trap formation by blocking of the interleukin-1 receptor.

Besides performing phagocytosis and degranulation, neutrophils are capable of eliminating microorganisms by releasing neutrophil extracellular traps (NETs). NET formation was found to be associated with increased mortality in sepsis. During sepsis levels of interleukin 1ß (IL-1ß), a cytokine, increases significantly and also was associated with increased mortality. Blocking of the interleukin 1 (IL-1) receptor by anakinra leads to less NET formation in gout patients. However, NET formation is crucial during infection by trapping pathogens and thereby slowing the process. Total or early blocking of cascades leading to NETs may lead to aggravation of infection in otherwise mild cases. The dose- and time-dependent effect of the IL-1 receptor antagonist anakinra was tested on spontaneous, lipopolysaccharide (LPS)-induced and phorbol-12-myristate 13-acetate (PMA)-induced formation of NETs in vitro. Quantitative detection of NETs was performed for NETspecific proteins and cell-free DNA. Immunostained microscopy imaging was used for visualization. Our study shows a dose- and time-dependent inhibitory effect of anakinra that involves the change of intracellular calcium mobilization on the formation of NETs in vitro for PMA-stimulated neutrophils but not for LPS-stimulated neutrophils. It may be useful for treatment of sepsis as part of a multimodal treatment concept, but it seems that timing and dose need to be carefully chosen.

Ultrasound-guided ilioinguinal-iliohypogastric block (ILIHB) or perifocal wound infiltration (PWI) in children: a prospective randomized comparison of analgesia quality, a pilot study.

BACKGROUND: Ilioinguinal-iliohypogastric block (ILIHB) is a well-established procedure for postoperative analgesia after open inguinal surgery in children. This procedure is effective and safe, especially when ultrasound is used. Data availability for comparing ultrasound-guided blocks versus wound infiltration is still weak. The study was designed to determine the efficacy of ultrasound-guided ILIHB (US-ILIHB) on postoperative pain control in pediatric patients following a inguinal daycase surgery, compared with perifocal wound infiltration (PWI) by the surgeon. METHODS: This randomized, double-blinded trail was conducted in pediatric patients aged from 6 months to 4 years. The total number of children included in the study was 103. Patients were allocated at random in two groups by sealed envelopes. The ILIHB group recieved 0,2% ropivacain for US-ILIHB after anesthesia induction. The PWI group recieved 0,2% ropivacain for PWI performed by a surgeon before wound closure. Parameters recorded included the postoperative pain score, pain frequency, time to first analgesics and consumption of analgesics. RESULTS: US-ILIHB significantly reduced the occurrence of pain within the first 24 h after surgery (7.7%, p = 0.01). Moreover, the pain-free interval until administration of the first dose of opioids was 21 min longer, on average (p = 0.003), following US-ILIHB compared to perifocal wound infiltration. 72% of children who received US-ILIHB did not require additional opioids, as compared to 56% of those who received PWI. CONCLUSION: Thus our study demonstrates that US-ILIHB ensures better postoperative analgesia in children and should be prioritized over postoperative PWI. TRAIL REGISTRATION: UIHBOPWIIC, DRKS00020987 . Registered 20 March 2020 - Retrospectivley registered.

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.

[Child abuse-reduction in the estimated number of unreported cases by restructuring a clinical child protection program]. / Kindeswohlgefährdung ­ Ausweitung des Hellfeldes durch Neukonzeption der klinischen Kinderschutzarbeit.

BACKGROUND: Identification of child abuse is a daily challenge in medical work. The estimated number of unreported cases of child abuse and neglect is high. OBJECTIVES: The aim of this study was to investigate the effectiveness of the redesigned clinical child protection program of a major German pediatric hospital and to improve programs in other hospitals for children and physicians through presentation of the advantages of the new structure. METHODS: All cases of child protection at the Altona Children's Hospital were retrospectively analyzed before and after restructuring of the clinic's child protection program for a two-year period each, and a comparison was made. The child protection program was restructured and the new program subsequently managed by a fulltime coordinator. RESULTS: The prevalence of both suspected and substantiated cases of child abuse was significantly higher after restructuring of the child protection program. Before the change, 24 cases were investigated, of which 23 were substantiated; afterward, 124 cases were investigated and 89 were substantiated. Despite the high number of false-positive suspected cases, stigmatization of the families during the clarification progress was avoided by using a very sensitive approach, and the family was not confronted until the suspicion was affirmed. CONCLUSION: The presented concept of child protection in medical clinics seems to facilitate a higher detection rate of child abuse cases. The reduction in the number of undetected cases and thereby prevention of possible escalation of abuse, as well as the decline in the immense social follow-up costs, justifies the increased personnel costs.

Degradation of Extracellular DNA Significantly Ameliorates Necrotizing Enterocolitis Severity in Mice.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most devastating diseases in neonates and is characterized by high morbidity and mortality. It has been suggested that neutrophils play a crucial role in NEC pathogenesis and contribute to the hyperinflammatory reaction after bacterial colonization, which ultimately induces NEC. The aim of this study was to investigate whether dissolution of neutrophil extracellular traps (NETs) by systemic DNase1 therapy reduces NEC manifestation and morbidity. METHODS: NEC was induced in neonatal mice by gavage feeding of lipopolysaccharide mixed in Neocate, followed by hypoxia q12 h for 5d. Inactivated DNase1 and DNase1 were administered intraperitoneally twice daily in the control and treatment groups, respectively, starting on day 5 for 72 h. Survival, NEC score, intestinal damage (Chiu score, malondialdehyde [MDA], glutathione peroxidase [GPx]), inflammation (neutrophil elastase [NE], myeloperoxidase [MPO], toll-like receptor 4 [TLR4]), and NETs markers (SYTOX orange, cell-free DNA [cfDNA], DNase, citrullinated Histone 3 [H3cit]) were then assessed. RESULTS: In total, 44 neonatal mice were used in the experiment. Mice in the treatment group demonstrated significantly reduced NEC rates (44 versus 86%, P = 0.029) and improved survival in comparison to controls (65 versus 35%, P = 0.01). Furthermore, mice treated with DNase1 showed significantly less tissue damage (cfDNA, Chiu score), oxidative stress (MDA, GPx), and inflammation (NE, MPO, H3cit, TLR4), which ultimately lead to a significant reduction in mortality. CONCLUSIONS: The results of the study indicate that systemic DNase1 treatment leads to a significant reduction in tissue damage, NEC severity, and mortality. Therefore, after validation of our findings in human subjects, DNase1 treatment should be considered as a therapeutic option in neonates diagnosed with NEC.

The spaced learning concept significantly improves training for laparoscopic suturing: a pilot randomized controlled study.

BACKGROUND: Spaced learning has been shown to be effective in various areas like traditional knowledge or motor skill acquisition. To evaluate the impact of implementation of the spaced learning concept in laparoscopic training was the aim of this study. METHODS: To evaluate the effectiveness of spaced learning, subjects were asked to perform four surgeon's square knots on a bowel model prior and post 3 h of hands-on training. All subjects were medical students and novice in laparoscopic suturing. Total time, knot stability (evaluated via tensiometer), suture accuracy, knot quality (Muresan score), and laparoscopic performance (Munz checklist) were assessed. Moreover, motivation was accessed using Questionnaire on Current Motivation. RESULTS: Twenty students were included in the study; after simple randomization, ten were trained using "spaced learning" concept and ten conservatively. Both groups had comparable baseline characteristics and improved after training significantly regarding all aspects assessed in this study. Subjects that trained via spaced learning were superior in terms of suture performance, knot quality, and suture strength. Ultimately, spaced learning significantly decreased anxiety and impression of challenge compared to controls. CONCLUSION: The spaced learning concept is very suitable for complex motor skill acquisition like laparoscopic suturing and knot tying. It significantly improves laparoscopic performance and knot quality as shown by the knot score and suture strength. Thus, we recommend to incorporate spaced learning into training courses and surgical programs.

[Undetected Cases of Non-Accidental Burns in Children - Preventive Strategies]. / Dunkelziffer nicht-akzidenteller thermischer Verletzungen im Kindesalter ­ Kinderschutzstrategien zur Reduktion.

BACKGROUND: Thermal injuries are a frequent cause of accidents within the pediatric population that may result in long periods of hospitalization as well as severe physical and mental impairment and lifelong consequences. Especially in infants, burns caused by scalding are the most common cause of injury. Beside accidental injuries, intential burns may also occur. It is of utmost importance to differentiate between intentional and accidental burns, yet the distinction can be very demanding for physicians, nurses and social workers. METHODS: In this retrospective multicenter study, thermally inflicted burns in Germany were analyzed over a period of 10 years. RESULTS: Data of 13.353 pediatric patients with thermal injuries from 32 hospitals were analyzed within the period of 2006 to 2015. The study results show that 0,5% of all burns were inflicted. This percentage seems to be an inadequate represention as compared to reported international surveys, which report an average of 10% of all burns being inflicted in pediatric patients. DISCUSSION: When comparing our results to international survey results, it can be assumed that a large number of child abuse cases go undetected within the German pediatric population. In particular awareness of intentional burns needs to be raised and detection strategies, as presented in this paper, implemented. CONCLUSION: In the future, a more precise collection of data of burned children is necessary to illustrate the true number of intentional pediatric burns in Germany. This has been implemented by the renewed pediatric burn registry of the German Society for Burn Treatment (DGV) and the working group "The severely burned child".