(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis ...aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz−Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments.
Very rare tumors (VRTs) in children and adolescents are orphan diseases defined by an annual incidence of <2/1000,000. For a long time, VRTs have been outside of clinical and research groups in the ...field of pediatric oncology. As a result, exchange of experience and development of therapeutic standards have not been promoted. After the foundation of several national VRT working groups and the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT), a virtual consultation system (VCS) has been established, which specifically aimed at facilitating access to clinical consultation in complicated cases of VRTs.
The VCS has been open to physicians. After initial registration, they can present VRT patients free of charge. Patient consent and data pseudonymization were mandatory. Within the VCS, disease specific interdisciplinary panel discussions with at least three experts from the EXPeRT group and partners have been opened, and at the end of the discussion, a written summary and recommendation was provided.
Between Mai 2017 and March 2023, 160 cases from 27 countries (20 European, 7 non-European) have been discussed in the VCS. The most common diagnoses were adrenocortical carcinoma, malignant skin tumors and malignant ovarian tumors. In a survey three months after panel discussion, more than 90% of requesting physicians evaluated the VCS to be easy to use, helpful and to have a significant impact on patient management.
A VCS may provide significant assistance in the management of children and adolescents with VRTs. Furthermore, it may help to overcome inequalities in access to adequate treatment in countries with lower health care system resources or without established VRT study groups. Therefore, EXPeRT will continue to support the VCS. For this purpose, the VRT panels have been integrated into the Clinical Patient Management System (CPMS) within the European Reference Network Initiative (ERN PAedCan).
•Very rare tumors (VRTs) in childhood and adolescence are orphan diseases.•Pediatric oncologists have limited experience in managing VRTs.•An international virtual consultation system (VCS) has been established for VRTs.•160 VCS consultations for VRTs illustrate the ability to promote quality of care.
Zusammenfassung
Wachstum und Entwicklung des menschlichen Körpers und seiner Organe sind fein abgestimmte Prozesse, die kontinuierlich durch zahlreiche Gene reguliert werden. Genetisch bedingte ...Defekte dieser Feinregulation können sich klinisch zum einen in Wachstumsstörungen, z. B. in Klein- oder Großwuchssyndromen, oder in Organfehlbildungen manifestieren. Zum anderen können sie, insbesondere bei Keimbahndefekten, ein erhöhtes Risiko für die Entwicklung einer Krebserkrankung bedingen. Insgesamt sind mehr als 50 Erkrankungen mit einer erhöhten Krebsprädisposition bekannt. In dieser Übersicht werden beispielhaft 3 für die Pädiatrie relevante Krebsprädispositionserkrankungen, die Neurofibromatose Typ 1, das Beckwith-Wiedemann-Syndrom und das DICER1-Syndrom, vorgestellt. Von entscheidender Bedeutung ist ein auf das zu erwartende Tumorspektrum angepasstes Screening dieser Patienten. Ziel ist es, die Entstehung bösartiger Tumoren frühzeitig erkennen zu können und dadurch mit weniger Therapieeinsatz eine bessere Prognose zu ermöglichen. Darüber hinaus muss die Krebsnachsorge die mögliche Entwicklung von Folgetumoren oder anderen Folgeerkrankungen in den Blick nehmen. Kenntnisse der onkologischen und nichtonkologischen Aspekte dieser Krebsprädispositionserkrankungen sind die Voraussetzung für eine angemessene ganzheitliche Betreuung dieser Patienten und damit für Kinderonkologen, pädiatrische Spezialisten sowie Allgemeinpädiater relevant.
Birch tar is one of the oldest adhesives known in human history. Its production has been discussed in the framework of early complex behaviours and sophisticated cognitive capacities. The precise ...production method used in the Palaeolithic remains unknown today. Arguments for or against specific production pathways have been based on efficiency or process complexity. No studies have addressed the question whether birch tar made with different techniques is more or less performant in terms of its properties. We therefore investigate the adhesive performance of birch tar made with three distinct methods: the open-air condensation method and two variations of underground structures that approximate the double-pot method in aceramic conditions. We use lap-shear testing, a standard mechanical test used for testing the strength of industrial adhesives. Tar made in 1 h with the condensation method has a shear strength similar to, although slightly higher than, tar made underground if the underground process lasts for 20 h. However, tars from shorter underground procedures (5 h) are significantly less strong (by a factor of about 3). These findings have important implications for our understanding of the relationship between the investment required for Palaeolithic birch tar production and the benefits that birch tar represented for early technology. In this regard, the simple and low-investment open-air condensation method provides the best ratio.
Abstract
Aims
Traffic noise may play an important role in the development and deterioration of ischaemic heart disease. Thus, we sought to determine the mechanisms of cardiovascular dysfunction and ...inflammation induced by aircraft noise in a mouse model of myocardial infarction (MI) and in humans with incident MI.
Methods and results
C57BL/6J mice were exposed to noise alone (average sound pressure level 72 dB; peak level 85 dB) for up to 4 days, resulting in pro-inflammatory aortic gene expression in the myeloid cell adhesion/diapedesis pathways. The noise alone promoted adhesion and infiltration of inflammatory myeloid cells in vascular/cardiac tissue, paralleled by an increased percentage of leucocytes with a pro-inflammatory, reactive oxygen species (ROS)-producing phenotype and augmented expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase type 2 (Nox2)/phosphorylation of nuclear factor ‘kappa light chain enhancer’ of activated B-cells (phospho-NFκB) in peripheral blood. Ligation of the left anterior descending artery resulted in worsening of cardiac function, pronounced cardiac infiltration of CD11b+ myeloid cells and Ly6Chigh monocytes, and induction of interleukin (IL) 6, IL-1β, CCL-2, and Nox2, being aggravated by noise exposure prior to MI. MI induced stronger endothelial dysfunction and more pronounced increases in vascular ROS in animals preconditioned with noise. Participants of the population-based Gutenberg Health Cohort Study (median follow-up:11.4 years) with incident MI revealed elevated C-reactive protein at baseline and worse left ventricular ejection fraction (LVEF) after MI in case of a history of noise exposure and subsequent annoyance development.
Conclusion
Aircraft noise exposure before MI substantially amplifies subsequent cardiovascular inflammation and aggravates ischaemic heart failure, facilitated by a pro-inflammatory vascular conditioning. Our translational results suggest that measures to reduce environmental noise exposure will be helpful in improving the clinical outcome of subjects with MI.
Key question
How does exposure to aircraft noise impact cardiovascular inflammation?
What is the impact of prior aircraft noise annoyance and inflammation in a mouse model of MI and in patients with incident MI?
Key finding
Aircraft noise exposure induces pro-inflammatory transcriptional changes in the vasculature and primes cardiovascular inflammation.
Aircraft noise exposure prior to MI worsens cardiac and vascular function.
Patients with incident MI have higher C-reactive protein levels at baseline and show worse left ventricular fraction when they had a history of aircraft noise exposure and annoyance.
Take-home-MessageAircraft noise exposure before MI substantially amplifies cardiovascular inflammation and aggravates cardiac impairment after MI.
Graphical Abstract
Graphical Abstract
Aircraft noise exposure leads to a systemic stress response with activation of myeloid cells and promoting adhesion and infiltration into cardiovascular tissue due to a pro-inflammatory, reactive oxygen species (ROS)-producing phenotype and an augmented expression of Nox2 and phospho-NFκB. Induction of myocardial infarction by permanent ligation of the left anterior descending artery results in worsening of cardiac function, pronounced cardiac infiltration, and increased mitochondrial ROS production aggravated by noise exposure prior to cardiac ischaemia. Created with BioRender.com.
Birch tar is the oldest synthetic substance made by early humans. The earliest such artefacts are associated with Neanderthals. According to traditional interpretations, their study allows ...understanding Neanderthal tool behaviours, skills and cultural evolution. However, recent work has found that birch tar can also be produced with simple processes, or even result from fortuitous accidents. Even though these findings suggest that birch tar per se is not a proxy for cognition, they do not shed light on the process by which Neanderthals produced it, and, therefore, cannot evaluate the implications of that behaviour. Here, we address the question of how tar was made by Neanderthals. Through a comparative chemical analysis of the two exceptional birch tar pieces from Königsaue (Germany) and a large reference birch tar collection made with Stone Age techniques, we found that Neanderthals did not use the simplest method to make tar. Rather, they distilled tar in an intentionally created underground environment that restricted oxygen flow and remained invisible during the process. This degree of complexity is unlikely to have been invented spontaneously. Our results suggest that Neanderthals invented or developed this process based on previous simpler methods and constitute one of the clearest indicators of cumulative cultural evolution in the European Middle Palaeolithic.
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