The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.

Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK) and high molecular weight kininogen (HK) interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients.

A team-based approach to type 2 diabetes and cardiovascular care.

The Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) program is an innovative, patient-centered system of care developed by the University Hospitals Harrington Heart and Vascular Institute in Cleveland, Ohio in the US for the management of high-risk patients with type 2 diabetes (T2D) and prediabetes at high risk for cardiovascular-kidney-metabolic (CKM) syndrome and its consequences. At its core, CINEMA is a multidisciplinary team of care experts, working together outside of traditional silos. The patient meets with the entire team up to 4 times each year to address all aspects of cardiovascular (CV) and T2D care.

Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells.

The cyclin D1-Cyclin-Dependent Kinases 4 and 6 (CDK4/6) complex is crucial for the development of melanoma. We previously demonstrated that targeting CDK4/6 using small molecule inhibitors (CDK4/6i) suppresses Braf melanoma growth in vitro and in vivo through induction of cellular senescence. However, clinical trials investigating CDK4/6i in melanoma have not yielded successful outcomes, underscoring the necessity to enhance the therapeutic efficacy of CDK4/6i.

Comment on: Toward an optimal contraception dosing strategy.

The optimal contraception dosing strategy proposed by Gavina et al. recently is a commendable attempt to model a complex physiological process with potenial to apply to real-life data. However, there is a need to take into account the real challenges that arise when moving from the theory to its practical application, and it is important that lessons learnt from clinical studies be taken into consideration in any theoretical modelling.

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.

Transitioning medically complex infants home: lessons learned from quality improvement efforts.

Objective: Decrease: 1) time from tracheostomy or gastrostomy tube placement to discharge home, and 2) avoidable readmissions within 7 days post-discharge, for medically complex infants.

Study Design: Five neonatology units and representatives from Medicaid and Managed Care Organizations participated. Measures included length of stay (LOS) from surgery to discharge, readmissions, and time from surgery to identifying home nursing.

Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Leadership training in emergency medicine: A national survey.

Background: Emergency medicine (EM) is a uniquely stressful environment in which leadership training could improve individual and team performance, patient outcomes, well-being, and EM career intentions. The primary aim was to evaluate EM-specific leadership training (EMLeaders) compared to no leadership training. A secondary comparison was with other forms of leadership training.

National Dermatological Surgery Sustainability Survey: An Evaluation of Healthcare Professional Beliefs and Practices.

Background: Dermatological surgery contributes to the large environmental impact of healthcare, but to date there are no data on the current sustainability practices, attitudes, or behaviours of UK and Republic of Ireland health professionals involved in skin surgery.

Objectives: We sought to evaluate this using a national sustainability questionnaire, organised by the British Society for Dermatological Surgery.

Methods: Over 12-weeks, a 17-item online questionnaire was distributed nationally to healthcare professionals involved in skin surgery.

Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-H-glucose, U-H-glycerol) and liver-specific genome-scale metabolic models (GEMs).

A single-chain variable fragment-based bispecific T-cell activating antibody against CD117 enables T-cell mediated lysis of acute myeloid leukemia and hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML-exclusive, non-HSPC-expressed cell-surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface-directed immunotherapy in this disease setting, time-limited combined immune-targeting of AML cells and healthy HSPCs, followed by hematopoietic stem cell transplantation (HSCT), might be a viable therapeutic approach.

Physical activity and sedentary behaviour interventions for people living with both frailty and multiple long-term conditions and their informal carers: a scoping review and stakeholder consultation.

Introduction: This scoping review mapped evidence on physical activity (including structured exercise) and sedentary behaviour interventions (interventions to reduce sedentary behaviour) in people living with both frailty and multiple long-term conditions (MLTCs) and their informal carers.

Methods: Ten databases and grey literature were searched from 2000 to October 2023. Two reviewers screened studies and one extracted data.

Type 1 Diabetes in care homes: A practical guide on management.

The primary purpose of the original NAPCHD project was to develop a national Strategic Document of Diabetes Care for Care Homes which has now been completed and well received as a worthwhile, sustainable, and effective guidance for delivering quality diabetes care in the UK. A Working Group of NAPCHD was established to produce a Position Statement on type 1 diabetes in care homes since this area was recommended as a topic to further develop. There are currently limited data on the prevalence and clinical outcomes associated with type 1 diabetes in care homes and management policies have been non-existent in the UK.

Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial.

Background: Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.

Multidimensional Sleep Health in Surrogate Decision-Makers of Critically Ill Patients.

Background: Supporting the sleep health of surrogate decision-makers of patients in the intensive care unit is a research priority. However, few studies have approached sleep health as a multidimensional construct, instead focusing on 1 or 2 dimensions in isolation.

Objective: To holistically examine the sleep health (satisfaction, timing, efficiency, duration) of surrogate decision-makers of critically ill patients.

Challenges posed by climate hazards to cardiovascular health and cardiac intensive care: implications for mitigation and adaptation.

Global warming, driven by increased greenhouse gas emissions, has led to unprecedented extreme weather events, contributing to higher morbidity and mortality rates from a variety of health conditions, including cardiovascular disease (CVD). The disruption of multiple planetary boundaries has increased the probability of connected, cascading, and catastrophic disasters with magnified health impacts on vulnerable populations. While the impact of climate change can be manifold, non-optimal air temperatures (NOTs) pose significant health risks from cardiovascular events.

A reproducible extended ex-vivo normothermic machine liver perfusion protocol utilising improved nutrition and targeted vascular flows.

Background: Normothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements.

Epigenetic aging differentially impacts breast cancer risk by self-reported race.

Background: Breast cancer (BrCa) is the most common cancer for women globally. BrCa incidence varies by age and differs between racial groups, with Black women having an earlier age of onset and higher mortality compared to White women. The underlying biological mechanisms of this disparity remain uncertain.

Preparing for responsive management versus preparing for renal dialysis in multimorbid older people with advanced chronic kidney disease (Prepare for Kidney Care): Study protocol for a randomised controlled trial.

Background: Chronic kidney disease (CKD) prevalence is steadily increasing, in part due to increased multimorbidity in our aging global population. When progression to kidney failure cannot be avoided, people need unbiased information to inform decisions about whether to start dialysis, if or when indicated, or continue with holistic person-centred care without dialysis (conservative kidney management). Comparisons suggest that while there may be some survival benefit from dialysis over conservative kidney management, in people aged 80 years and over, or with multiple health problems or frailty, this may be at the expense of quality of life, hospitalisations, symptom burden and preferred place of death.

Assessment of communication skills in health professions education; Ottawa 2024 consensus statement.

Despite the increasing inclusion of communication skills in accreditation standards and an increase in time dedicated to teaching these skills, communication is often regarded as a separate skill and is therefore, not consistently represented in overall systems of assessment in Health Professions Education (HPE). The ascendence of competency-based medical education, programmatic assessment, artificial intelligence, and widespread use of telehealth, alongside changing patient expectations warrant an update in thinking about the assessment of communication skills in health professions education. This consensus statement draws on existing literature, expert pinion, and emerging challenges to situate the assessment of communication skills in the contemporary health professions education context.