Systematic Review of Ex Vivo and In Vivo Pharmacokinetic Studies of Drugs Commonly Used During Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving treatment for critically ill patients in cardiac or respiratory failure refractory to conventional treatment. Patients on an ECMO circuit (pump, oxygenator, tubing) require numerous medications including sedatives, analgesics, cardioactive medications, and anticonvulsants. Currently, there are few dosing guidelines to optimize pharmacotherapy in this situation.

Decoding the connection: unraveling the role of gut microbiome in fibromyalgia.

The gut microbiome is emerging as a critical player in the pathophysiology of fibromyalgia, offering mechanistic insights as well as potential diagnostic and therapeutic applications.

What are the potential mechanisms of fatigue-induced skeletal muscle hypertrophy with low-load resistance exercise training?

High-load resistance exercise (>60% of 1-repetition maximum) is a well-known stimulus to enhance skeletal muscle hypertrophy with chronic training. However, studies have intriguingly shown that low-load resistance exercise training (RET) (≤60% of 1-repetition maximum) can lead to similar increases in skeletal muscle hypertrophy as compared to high-load RET. This has raised questions about the underlying mechanisms for eliciting the hypertrophic response with low-load RET.

Non-Allergist Delabeling - Should penicillin allergy delabeling only be performed by allergists?

Penicillin allergy labels (PAL) are common but rarely correspond with a patient's likelihood to tolerate penicillin. This results in unnecessary penicillin avoidance in many patients, driving numerous negative health outcomes. Evaluation strategies for PAL are driven by risk stratification and include a spectrum of modalities such as delabeling without any testing, direct oral challenge, and skin testing followed by challenge testing.

Adults living with dementia and chronic wounds, wound types, care challenges, and impact across dementia stages: A scoping review protocol.

Objective: The objective of this scoping review is to map the existing evidence on the epidemiology, care challenges, and impacts of various wound types among individuals living with dementia across different stages of the disease.

Introduction: Dementia is a growing global health concern, projected to rise significantly as the population ages. This condition not only affects cognitive function but also increases the risk of chronic wounds in part due to impairments in mobility, self-care, and communication.

Exploring cytokine outputs for diagnostics in drug reaction with eosinophilia and systemic symptoms (DRESS).

Background: In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.

Methods: Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report.

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

Identification of a Founder GLDN Variant Associated With "Lethal" Arthrogryposis in Nunavik Inuit: Implications for Obstetrical and Long-Term Survivors' Management.

Biallelic variants in GLDN have recently been associated with lethal congenital contracture syndrome 11 (LCCS11), a form of fetal akinesia deformation sequence (FADS) with high neonatal mortality. In this report, we describe five individuals from two Canadian Inuit families originating from different communities in Nunavik all affected with FADS and harboring a rare homozygous missense variant, [NM_181789.4:c.

HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.

We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.

PTSD Coach as an early mobile intervention to improve cancer-related anxiety and psychosocial oncology uptake in patients newly diagnosed with head and neck cancer: pilot randomized controlled trial.

Background: This pilot study aimed to provide supportive evidence for the feasibility of conducting a full-scale intervention trial with patients newly diagnosed with head and neck cancer (HNC). This included assessing the acceptability and potential usefulness of the PTSD Coach mobile app as an early self-management intervention that gives information about anxiety symptoms, offers self-assessment of symptoms with feedback, tools to self-manage anxiety, and connects to support.

Methods: A three-arm randomized controlled trial was conducted.

Can knowledge-based planning models validated on ethnically diverse patients lead to global standardisation of external beam radiation therapy for locally advanced cervix cancer?

Background And Purpose: Knowledge-based planning (KBP) can consistently and efficiently create high-quality Volumetric Arc Therapy (VMAT) plans for cervix cancer. This study describes the cross-validation of two KBP models on geographically distinct populations and their comparison to manual plans from 67 centers. The purpose was to determine the universal applicability of a generic KBP model.

HPV vaccination and anal HPV infection in gay, bisexual, and other men who have sex with men.

Background: Gay, bisexual, and other men who have sex with men (gbMSM) have a higher risk of human papillomavirus (HPV) infection and related diseases and would benefit from preventive measures such as HPV vaccination. We assessed the association between HPV vaccination and anal HPV infection in HIV-negative gbMSM and gbMSM living with HIV from the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection study.

Methods: Participants attended 7 visits over 12 months where they provided a nurse-collected anal sample and self-completed a questionnaire on risk factors and HPV vaccination.

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.

Unique clones secrete populations of extracellular vesicles with unique protein profile and variable infectious capability.

The study of extracellular vesicles has become an incredibly important field of study, but the inherent heterogeneity of these vesicles continues to make their study challenging. The genetic variability and well-documented protocols for the growth and vesicle isolation from parasites provide a unique opportunity to compare the heterogeneity of different populations secreted by clones. was cultured on solid SDM agar plates and 8 clonal colonies were selected.

Use of the moving epidemic method to guide the launch of palivizumab immunization campaigns for respiratory syncytial virus in Québec, Canada.

Objective: The COVID-19 pandemic disrupted the seasonal transmission pattern of respiratory syncytial virus (RSV), challenging the launch of palivizumab immunization campaigns. This study explored the performance of the moving epidemic method (MEM) to guide the launch of such campaigns.

Methods: Data were collected through a continuous RSV surveillance system (07/2013‒03/2022) in Québec, Canada.

Hemoglobin A1c and abdominal obesity as predictors of diabetes and ASCVD in individuals with prediabetes in UK Biobank: a prospective observational study.

Objectives: Whether "prediabetes" merits particular clinical attention beyond the management of associated risk factors is controversial, particularly given the expansion of the definition of prediabetes from HbA1c 6.0-6.4% to 5.

Improving implementation of needle and syringe programmes to expand, scale up, and sustain evidence-based prevention interventions for HIV and hepatitis C in prisons.

The 1990 resolution by the UN General Assembly committed member states to provide health-care equity for people in prison, who are included in the global goals to control HIV and eliminate hepatitis C virus (HCV) by 2030. WHO has set ambitious HCV elimination targets by including people who inject drugs (PWID), yet has not prioritised PWID who are incarcerated, a substantial population who have or are at risk for HCV infection. Human rights principles of health-care equity stipulate that "prisoners should enjoy the same standards of health care that are available in the community, without discrimination on the grounds of their legal status".

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).