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.

A comprehensive clinical guide for Pneumocystis jirovecii pneumonia: a missing therapeutic target in HIV-uninfected patients.

INTRODUCTION: Pneumocystis jirovecii is an opportunistic, human-specific fungus that causes Pneumocystis pneumonia (PCP). PCP symptoms are non-specific. A patient with P. jirovecii and another lung infection faces a diagnostic challenge. It may be difficult to determine which of these agents is responsible for the clinical symptoms, preventing effective treatment. Diagnostic and treatment efforts have been made more difficult by the rising frequency with which coronavirus 2019 (COVID-19) and PCP co-occur. AREAS COVERED: Herein, we provide a comprehensive review of clinical and pharmacological recommendations along with a literature review of PCP in immunocompromised patients focusing on HIV-uninfected patients. EXPERT OPINION: PCP may be masked by identifying co-existing pathogens that are not necessarily responsible for the observed infection. Patients with severe form COVID-19 should be examined for underlying immunodeficiency, and co-infections must be considered as co-infection with P. jirovecii may worsen COVID-19's severity and fatality. PCP should be investigated in patients with PCP risk factors who come with pneumonia and suggestive radiographic symptoms but have not previously received PCP prophylaxis. PCP prophylaxis should be explored in individuals with various conditions that impair the immune system, depending on their PCP risk.

Considerations for Insulin-Treated Type 2 Diabetes Patients During Hospitalization: A Narrative Review of What We Need to Know in the Age of Second-Generation Basal Insulin Analogs.

With the availability of second-generation basal insulin analogs, insulin degludec (100 and 200 units/ml [degludec]) and insulin glargine 300 units/ml (glargine U300), clinicians now have long-acting, efficacious treatment options with stable pharmacokinetic profiles and associated low risks of hypoglycemia that may be desirable for many patients with type 2 diabetes. In this narrative review, we summarize the current evidence on glycemic control in hospitalized patients and review the pharmacokinetic properties of degludec and glargine U300 in relation to the challenges these may pose during the hospitalization of patients with type 2 diabetes who are receiving outpatient regimens involving these newer insulins. Their increased use in clinical practice requires that hospital healthcare professionals (HCPs) have appropriate protocols to transfer patients from these second-generation insulins to formulary insulin on admission, and ensure the safe discharge of patients and transition back to degludec or glargine U300. However, there is no guidance available on this. Based on the authors' clinical experience, we identify key issues to consider when arranging hospital care of such patients. We also summarize the limited available evidence on the potential utility of these second-generation basal insulin analogs in the non-critical inpatient setting and identify avenues for future research. To address current knowledge gaps, it is important that HCPs are educated about the differences between standard formulary insulins and second-generation insulins, and the importance of clear communication during patient transitions.