31 research outputs found

    Frequency of neuroimaging for pediatric minor brain injury is determined by the primary treating medical department

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

    Prenatal treatment with rosiglitazone attenuates vascular remodeling and pulmonary monocyte influx in experimental congenital diaphragmatic hernia

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    Publication history: Accepted - 23 October 2018; Published online - 12 November 2018.Introduction Extensive vascular remodeling causing pulmonary hypertension (PH) represents a major cause of mortality in patients with congenital diaphragmatic hernia (CDH). The chemokine monocyte chemoattractant protein-1 (MCP-1) is a biomarker for the severity of PH and its activation is accompanied by pulmonary influx of monocytes and extensive vascular remodeling. MCP-1 activation can be reversed by application of rosiglitazone (thiazolidinedione). We performed this study to evaluate the role of MCP-1 for the pathogenesis of PH in experimental CDH. We hypothesized that vascular remodeling and MCP-1 activation is accompanied by pulmonary influx of fetal monocytes and can be attenuated by prenatal treatment with rosiglitazone. Methods In a first set of experiments pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D21 and divided into CDH and control. Quantitative real-time polymerase chain reaction, Western blot (WB), and immunohistochemistry (IHC) were used to evaluate MCP-1 expression, activation, and localization. Quantification and localization of pulmonary monocytes/macrophages were carried out by IHC. In a second set of experiments nitrofen-exposed dams were randomly assigned to prenatal treatment with rosiglitazone or placebo on D18+D19. Fetal lungs were harvested on D21, divided into control, CDH+rosiglitazone, and CDH+placebo and evaluated by WB as well as IHC. Results Increased thickness of pulmonary arteries of CDH fetuses was accompanied by increased systemic and perivascular MCP-1 protein expression and significantly higher amounts of pulmonary monocytes/macrophages compared to controls (p<0.01). These effects were reversed by prenatal treatment with rosiglitazone (p<0.01 vs. CDH+P; control). Conclusion Prenatal treatment with rosiglitazone has the potential to attenuate activation of pulmonary MCP-1, pulmonary monocyte influx, and vascular remodeling in experimental CDH. These results provide a basis for future research on prenatal immunomodulation as a novel treatment strategy to decrease secondary effects of PH in CDH.This work was supported by Children’s Medical & Research Foundation, Dublin, Ireland, https://cmrf.org/, Senior Research Fellowship JG, awarded to JG; German Research Foundation and Leipzig University within the program of Open Access Publishing, awarded to JG, https://www.ub.uni-leipzig.de/open-science/publikationsfonds/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA

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    Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host–pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H(2)O(2)), but its consequences on extracellular pathogens are unknown. Here we show that H(2)O(2), released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches

    Activation of Regulatory T Cells during Inflammatory Response Is Not an Exclusive Property of Stem Cells

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    BACKGROUND: Sepsis and systemic-inflammatory-response-syndrome (SIRS) remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific. METHODOLOGY/PRINCIPAL FINDINGS: Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS) in wild type mice (C3H/HeN). Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS) and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BDℱ Cytometric Bead Arrays), T cell subpopulations (flow-cytometry) and pulmonary neutrophil influx (immunohistochemistry). To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK) was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice. CONCLUSIONS/SIGNIFICANCE: The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not exclusive attributes of stem cells

    Global Development of Research on Anorectal Malformations over the Last Five Decades: A Bibliometric Analysis

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

    Hyperspectral Imaging—A Novel Tool to Assess Tissue Perfusion and Oxygenation in Esophageal Anastomoses

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    Anastomotic stricture and leakage are common complications after repair of esophageal atresia (EA). A compromised perfusion of the anastomosis is a contributing factor. Hyperspectral imaging (HSI) is an ultrashort noninvasive method to measure tissue perfusion. We present two cases of with tracheoesophageal fistula (TEF)/EA repair, in whom we applied HSI: the first patient was a newborn with EA type C who underwent open TEF repair. The second one had an EA type A and cervical esophagostomy, in whom we performed gastric transposition. In both patients, HSI confirmed a good tissue perfusion of the later anastomosis. The postoperative course was uneventful and both patients are on full enteral feeds. We conclude that HSI is a safe and noninvasive tool that allows near real-time assessment of tissue perfusion and can contribute to the identification of the optimal anastomotic region during pediatric esophageal surgery

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

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    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

    Percentage of regulatory T cells after AFS cell application.

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    <p>The percentage of Foxp3<sup>+</sup> lymphocytes was significantly increased in the pool of CD4<sup>+</sup>CD25<sup>+</sup> lymphocytes after application of homAFS compared to saline-treated positive-controls (+) and non-endotoxemic negative-controls (−).</p

    Preparation of vital AFS cells and homogenized AFS cells.

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    <p>10<sup>6</sup> vital AFS cells (vitAFS) were prepared in 0.7 ml sterile phosphate buffered saline (PBS) for intraperitoneal injection in mice randomly assigned to the vitAFS group (2 h after LPS challenge). For the preparation of homogenized AFS cells, 10<sup>6</sup> vital AFS cells underwent 5 min cell-disruption in 0.7 ml PBS prior to injection by sonication.</p
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