Pathogenesis,immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI Position Paper

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately 4 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.     

When should I eat: A circadian view on food intake and metabolic regulation

The circadian clock is a hierarchical timing system regulating most physiological and behavioral functions with a period of approximately 24 h in humans and other mammalian species. The circadian clock drives daily eating rhythms that, in turn, reinforce the circadian clock network itself to anticipate and orchestrate metabolic responses to food intake. Eating is tightly interconnected with the circadian clock and recent evidence shows that the timing of meals is crucial for the control of appetite and metabolic regulation. Obesity results from combined long-term dysregulation in food intake (homeostatic and hedonic circuits), energy expenditure, and energy storage. Increasing evidence supports that the loss of synchrony of daily rhythms significantly impairs metabolic homeostasis and is associated with obesity. This review presents an overview of mechanisms regulating food intake (homeostatic/hedonic) and focuses on the crucial role of the circadian clock on the metabolic response to eating, thus providing a fundamental research axis to maintain a healthy eating behavior.     

Epithelial–mesenchymal transition and cancer stem cells: A route to acquired cisplatin resistance through epigenetics in HNSCC

Chemoresistance is associated with tumor recurrence, metastases, and short survival. Cisplatin is one of the most used chemotherapies in cancer treatment, including head and neck squamous cell carcinoma (HNSCC), and many patients develop resistance. Here, we established cell lines resistant to cisplatin to better understand epigenetics and biological differences driving the progression of HNSCC after treatment. Cisplatin resistance was established in CAL-27 and SCC-9 cell lines. Gene expression of HDAC1, HDAC2, SIRT1, MTA1, KAT2B, KAT6A, KAT6B, and BRD4 indicated the cisplatin activates the epigenetic machinery. Increases in tumor aggressiveness were detected by BMI-1 and KI-67 in more resistant cell lines. Changes in cellular shape and epithelial–mesenchymal transition (EMT) activation were also observed. HDAC1 and ZEB1 presented an opposite distribution with down-regulation of HDAC1 and up-regulation of ZEB1 in the course of chemoresistance. Up-regulation of ZEB1 and BMI-1 in patients with HNSCC is also associated with a poor response to therapy. Cancer stem cells (CSC) population increased significantly with chemoresistance. Down-regulation of HDAC1, HDAC2, and SIRT1 and accumulation of Vimentin and ZEB1 were observed in the CSC population. Our results suggest that in the route to cisplatin chemoresistance, epigenetic modifications can be associated with EMT activation and CSC accumulation which originate more aggressive tumors.     

Risk profile and mode of transmission of Mpox: A rapid review and individual patient data meta-analysis of case studies

Since May 2022, an outbreak of Mpox in non-endemic countries has become a potential public health threat. The objective of this rapid review was to examine the risk profile and modes of transmission of Mpox. PubMed, Web of Science, and Scopus were searched from inception through July 30 to collect case reports/series on patients with Mpox infection. For meta-analysis, data on the total number of participants and deaths by binary categories of exposure (age, sex, country, other co-infections or existing conditions, and mode of contagion) were used. A total of 62 studies (4659 cases) were included. Most cases came from Africa (84.3%), followed by Europe (13.9%). In 63.6% of the cases, the mode of contagion was human contact, while 22.8% of the cases were by animal contact, and 13.5% were unknown or not reported. The mortality rate was 6.5% throughout these studies. The risk of mortality was higher in the younger age group (risk difference: 0.19; 95% CI: 0.02–0.36), in cases with other co-infections or current chronic conditions (risk difference: 0.03; 95% CI: 0.01–0.05) and in the category of low- and middle-income countries (risk difference: 0.06; 95% CI: 0.05–0.08). There were no significant differences with respect to sex or mode of contagion. These results help to understand the major infection pathways and mortality risk profiles of Mpox and underscores the importance of preventing outbreaks in specific settings, especially in settings densely populated by children, such as day care centres and schools.