2024 Update of the RECOVER-Adult Long COVID Research Index.

Importance: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves.

Objective: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities.

A targeted single mutation in influenza A virus universal epitope transforms immunogenicity and protective immunity via CD4 T cell activation.

CD4 T cells are central to adaptive immunity. Their role in cross-protection in viral infections such as influenza and severe acute respiratory syndrome (SARS) is well documented; however, molecular rules governing T cell receptor (TCR) engagement of peptide-human leukocyte antigen (pHLA) class II are less understood. Here, we exploit an aspect of HLA class II presentation, the peptide-flanking residues (PFRs), to "tune" CD4 T cell responses within an in vivo model system of influenza.

Clinical course and management of COVID-19 in the era of widespread population immunity.

The clinical implications of COVID-19 have changed since SARS-CoV-2 first emerged in humans. The current high levels of population immunity, due to prior infection and/or vaccination, have been associated with a vastly decreased overall risk of severe disease. Some people, particularly those with immunocompromising conditions, remain at risk for severe outcomes.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.

Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.

Design, Setting, And Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19.

The Prevalence of Metabolic Syndrome and Its Components in Firefighters: A Systematic Review and Meta-Analysis.

Previous studies consistently report a high prevalence of cardiovascular disease (CVD) risk factors among firefighters. However, the clustering of CVD risk factors, defined as metabolic syndrome (MetSyn), has received little attention by comparison. Therefore, the aim of this study was to estimate the pooled prevalence of MetSyn among firefighters.

Inhibitory IL-10-producing CD4 T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1.

Inhibitory CD4 T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity. However, the mechanisms that underpin the development of these regulatory cells, especially in the context of ongoing antigen exposure, have remained obscure. To address this knowledge gap, we undertook a comprehensive functional, phenotypic, and transcriptomic analysis of interleukin (IL)-10-producing CD4 T cells induced by chronic infection with murine cytomegalovirus (MCMV).

PI3K Isoform Immunotherapy for Solid Tumours.

Improving the anti-tumour T cell response as a consequence of immunotherapy can result in eradication of tumour burden, however, the majority of patients fail with current treatment regimens and so novel immunotherapies with greater efficacy and improved tolerability are needed. The phosphoinositide-3-kinase (PI3K) family members that are directly involved in cell signalling comprise PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, with the latter two isoforms expressed primarily by leukocytes. The survival and optimal function of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs) is dependent on PI3Kδ, whereas tumour-associated macrophages (TAMs), use PI3Kγ.

Use of biomarkers to individualize antimicrobial therapy duration: a narrative review.

Background: Reducing the overuse of antimicrobials is imperative for the sake of minimizing antimicrobial-associated adverse effects, optimizing resource utilization, and curtailing the rise in multidrug-resistant organisms. Biomarkers reflect the host responses to infection and may assist with minimizing unnecessary antimicrobial usage.

Objectives: To review the literature pertaining to the performance of biomarkers specifically used to guide the duration of antimicrobial therapy (AMT).

Treg-driven tumour control by PI3Kδ inhibition limits myeloid-derived suppressor cell expansion.

Background: Recent studies have demonstrated that blocking the PI3Kδ signalling enzyme (by administering a small molecule inhibitor, PI-3065) can potently improve the anti-tumour T-cell response through direct inhibition of Tregs. This treatment also has a negative impact on MDSC numbers but the primary mechanism driving this effect has remained unclear.

Methods: The 4T1 breast cancer mouse model was used in combination with PI-3065 to gain insights into the effect of PI3Kδ inhibition on MDSCs.

The Clamping of End-Tidal Carbon Dioxide Does Not Influence Cognitive Function Performance During Moderate Hyperthermia With or Without Skin Temperature Manipulation.

Increases in body temperature from heat stress (i.e., hyperthermia) generally impairs cognitive function across a range of domains and complexities, but the relative contribution from skin versus core temperature changes remains unclear.

Native Aortic Root Thrombus in 3-Year-Old Fontan Patient with Hypoplastic Left Heart Syndrome: Presentation and Echocardiographic Findings of This Life-Threatening Complication.

• Native aortic root thrombus is a life-threatening complication in patients with HLHS. • Echo evaluation of the native aortic root is an important consideration. • Echo monitoring is a useful tool for assessment of thrombus response to therapy.

Standardized Training for Physicians Practicing Pediatric Cardiac Critical Care.

Objectives: In the vast majority of Children's Hospitals, the critically ill patient can be found in one of three locations: the PICU, the neonatal ICU, and the cardiac ICU. Training, certification, and maintenance of certification for neonatology and critical care medicine are over seen by the Accreditation Council for Graduate Medical Education and American Board of Pediatrics. There is no standardization of training or oversight of certification and maintenance of certification for pediatric cardiac critical care.

The effects of acute dopamine reuptake inhibition on cognitive function during passive hyperthermia.

Dopamine activity can modulate physical performance in the heat, but less is known about its effects on cognition during thermal stress. Twelves males completed a randomized, double-blinded protocol consisting of oral ingestion of 20 mg of methylphenidate (MPH) or placebo (lactose pill) during passive heating using a water-perfused suit (water temperature ∼49 °C). To identify the impact of peripheral versus central thermal strain, a cognitive test battery was completed at 4 different thermal states: baseline (BASE; 37.

Recurrent Multifocal Infection in an Immunocompromised Patient: A Case Report and Review.

A young woman with mixed connective tissue disease complicated by erosive arthritis, secondary hypogammaglobulinemia due to rituximab, and a history of many infectious complications developed multiple nonhealing wounds, polyarticular joint pain, and leukocytosis. Radiographic studies demonstrated multiple scattered areas of osteomyelitis and complex abscesses. Purulent fluid drained from multiple sites did not yield a microbiologic diagnosis by standard culture technique, but was ultimately identified using 16 S ribosomal RNA gene amplification and sequencing.

Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion.

Although metastatic disease is responsible for the majority of cancer deaths, tests of novel immunotherapies in mouse tumour models often focus on primary tumours without determining whether these therapies also target metastatic disease. This study examined the impact of depleting Foxp3 regulatory T cells (Treg), on lung metastases, using a mouse model of breast cancer. After Treg-depletion, generation of an immune response to the primary tumour was a critical determinant for limiting development of metastasis.

Characteristics and Outcomes of Coronavirus Disease Patients under Nonsurge Conditions, Northern California, USA, March-April 2020.

Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.

Treatment optimization for HIV/HCV co-infected patients.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections affect millions of persons around the globe and cause profound morbidity and mortality. A major intersection exists between these two epidemics, with HCV infection being more common in persons with HIV than in the general population, largely due to shared routes of transmission. HCV co-infection increases risk for liver- and non-liver-related morbidity and mortality, making HCV treatment a priority in HIV co-infected persons, but the treatment of HCV in co-infected patients has been daunting for multiple reasons.

Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults.

Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities.

Investigating presentations and outcomes of a joint HIV-renal clinic.

Introduction: HIV patients are at risk of renal dysfunction directly from HIV, indirectly from chronic inflammation as well as from antiretroviral drug toxicity. In particular, tenofovir (TDF) has been associated with proximal renal tubular dysfunction. A joint HIV-renal clinic was set up in 2009 to facilitate a timely review and minimize additional follow-up appointments.