Wirkung von Chlorhexidin auf Fibroblasten nach Kontakt mit parodontopathogenen Bakterien

Chlorhexidin spielt eine bedeutende Rolle in der Prophylaxe und Therapie parodontaler Erkrankungen. In einer In-vitro-Studie wurde die Wirkung von elf chlorhexidinhaltigen Mundspüllösungen auf die Interaktion von Aggregatibacter actinomycetemcomitans (A.a.) und Porphyromonas gingivalis (P.g.) mit humanen gingivalen Fibroblasten untersucht. Es wurden Tests zur antimikrobiellen Wirksamkeit der Lösungen, zur Freisetzung proinflammatorischer Interleukine und zu zytotoxischen Effekten durchgeführt. Alle geprüften Chlorhexidinlösungen wiesen gute antimikrobielle Eigenschaften auf. Frisch hergestellte Lösungen erzielten bessere Ergebnisse als im Handel erhältliche Präparate. Ein Zusammenhang zwischen Konzentration, ergänzenden Zusätzen und der Wirksamkeit der Lösungen bestand nicht. Der keimabtötende Effekt gegenüber P. gingivalis war ausgeprägter als gegen A.a. Als Parameter für die Entzündungsreaktion wurde die Freisetzung von IL-6 und IL-8 aus Fibroblasten bestimmt. Es kam zur Reduktion der durch A.a. stimulierten Interleukinfreisetzung nach Einwirkung der Spüllösungen. Bei Versuchen mit P.g. zeigte sich ein Anstieg der niedrigen Interleukinspiegel nach Kontakt mit Mundspüllösungen, bedingt durch die Hemmung der interleukinspaltenden Gingipaine. Auch antimikrobielle Effekte und die Zytotoxizität beeinflussten die Freisetzung von Interleukinen. Bei Untersuchungen zur Zytotoxizität wurden zellschädigende Effekte aller untersuchten Mundspüllösungen auf Gingivafibroblasten nachgewiesen. Es bestand ein Zusammenhang zwischen steigender Chlorhexidinkonzentration und vermehrter Zellschädigung. Die Ergebnisse der Studie bestätigen die gute Wirksamkeit von Chlorhexidin, aufgrund der Zytotoxizität sollte die Dauer der Anwendung in der Mundhöhle jedoch eingeschränkt werden. Eine gezielte Kurzzeitanwendung niedrig konzentrierter Lösungen in der Prophylaxe und Therapie ist zu bevorzugen

Design, Implementation and Evaluation of a Manned-Unmanned Teaming Concept for Fighter Jet Missions

In the proposed presentation, we want to give an overview of our research in the domain of Manned-Unmanned-Teaming (MUM-T) for fighter jets. The Institute of Flight Systems (IFS) aims to develop a concept of MUM-T for airborne military operations by means of work system analysis and cockpit simulation of full missions. From that, we develop solutions to the main challenges of MUM-T. In future operating environment, mixed teams of manned and unmanned fighter jets might pursue mission goals which formerly were executed by exclusively manned platforms. This requires unmanned aerial vehicles (UAVs) to perform tasks from operations such as Air Interdiction (AI), Suppression of Enemy Air Defence (SEAD) or Offensive Counter Air (OCA). Furthermore, emerging technologies such as swarming enable new operational uses and roles in Combined Air Operations Course (COMAO). However, the implementation of such a operational concept bears major challenges for human factor engineering, system design and cognitive automation

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10$^{-10}$), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10$^{-10}$). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Esophageal Perforation and EVAC in Pediatric Patients: A Case Series of Four Children

Introduction: In pediatric patients, esophageal perforation (EP) is rare but associated with significant morbidity and mortality rates of up to 20–30%. In addition to standard treatment options, endoscopic esophageal vacuum-assisted closure (EVAC) therapy has shown promising results, especially in adult patients. Thus far, the only data on technical success and effectiveness of EVAC in pediatric patients were published in 2018 by Manfredi et al. at Boston Children's Hospital. The sparse data on EVAC in children indicates that this promising technique has been barely utilized in pediatric patients. More data are needed to evaluate efficacy and outcomes of this technique in pediatric patients. Method: We reviewed five cases of therapy using EVAC, ArgyleTM Replogle Suction Catheter (RSC), or both on pediatric patients with EP in our institution between October 2018 and April 2020. Results: Five patients with EP (median 3.4 years; 2 males) were treated with EVAC, RSC, or a combination. Complete closure of EP was not achieved after EVAC alone, though patients' health stabilized and inflammation and size of EP decreased after EVAC. Four patients then were treated with RSC until the EP healed. One patient needed surgery as the recurrent fistula did not heal sufficiently after 3 weeks of EVAC therapy. Two patients developed stenosis and were successfully treated with dilatations. One patient treated with RSC alone showed persistent EP after 5 weeks. Conclusion: EVAC in pediatric patients is technically feasible and a promising method to treat EP, regardless of the underlying cause. EVAC therapy can be terminated as soon as local inflammation and C-reactive protein levels decrease, even if the mucosa is not healed completely at that time. A promising subsequent treatment is RSC. An earlier switch to RSC can substantially reduce the need of anesthesia during subsequent treatments. Our findings indicate that EVAC is more effective than RSC alone. In some cases, EVAC can be used to improve the tissues condition in preparation for a re-do surgery. At 1 year after therapy, all but one patient demonstrated sufficient weight gain. Further prospective studies with a larger cohort are required to confirm our observations from this small case series

Hyperadiponectinemia During Infliximab Induction Therapy in Pediatric Crohn Disease

Objectives: The inflammatory process in Crohn disease (CD) involves the visceral fat, characterized by adipocyte hyperplasia and altered adipose tissue and serum concentrations of tumor necrosis factor (TNF), leptin, adiponectin and resistin. We investigated the effect of anti-TNF therapy with infliximab (IFX) on serum adipokine levels in pediatric CD. Methods: Serum concentrations of resistin (ng/mL), leptin (ng/mL), and total adiponectin (mu g/mL) were assessed by enzyme-linked immunosorbent assays (ELISA) in 18 pediatric CD patients (mean age 15.0 +/- 1.5 years) before first, second, and fourth IFX infusion (weeks 0, 2, and 14) and compared with baseline values from sex- and BMI-matched healthy controls (HC, mean age 13.4 +/- 1.6 years). Results: At baseline, CD patients (mean age 15.0 +/- 1.5 years, 10 of 18 boys) compared with HC (13.4 +/- 1.6 years, 7 of 15 boys) had higher resistin levels (median 14.7 ng/mL, range 5.1-50.5 vs 7.3 ng/mL, 0.5-14.5);P = 0.0002). At weeks 2 and 14, resistin decreased to 6.9 ng/mL (2.9-16.8) (P < 0.0001) and 9.2 ng/mL (4.1-20.6;P = 0.0011), respectively. Leptin and adiponectin were comparable between patients and HC at baseline. Leptin increased in girls from 9.5 ng/mL (4.0-30.1) to 16.0 ng/mL (7.9-35.2;P = 0.0156) and 17.2 ng/mL (10.8-26.8;P = 0.1953) at weeks 0, 2, and 14 respectively;with a trend in boys from 2 (0.6-12.9) to 2.8 (1.7-8.6;P = 0.0840) and 3.3 (1.34.6;P = 0.1309). Adiponectin peaked initially from 7.8 mu g/mL (4.6-11.9) at week 0 to 9.2 mu g/mL (4.1-20.7;P = 0.0005) at week 2 and thereafter fell to 6.5 mu g/mL (3.0-12.7;P = 0.0182) at week 14. Conclusions: TNF blockade is associated with changes in circulating adipokines. The marked early increase of the potent anti-inflammatory adiponectin may contribute to the rapid response to IFX in CD

The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease

Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel disease (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histological features of Crohn’s disease, ulcerative colitis, or IBD unclassified. Defects in interleukin-10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histological and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extraintestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. In addition, we provide approaches for identifying patients likely to have these disorders. We also discuss classic approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects

The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction

Background: Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re‐introduction and the influence of maintenance enteral nutrition. Aims: To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. Methods: Children with Crohn's disease were followed during exclusive enteral nutrition and during food‐reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food‐reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3. Results: Sixty‐six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index &lt;12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P &lt; .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P &lt; .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non‐users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: −0.573, P = .041), kcals (rho: −0.584, P = .036) and % energy intake (rho: −0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission. Conclusions: The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission