Guidelines International Network: Principles for Use of Artificial Intelligence in the Health Guideline Enterprise.

Description: Artificial intelligence (AI) has been defined by the High-Level Expert Group on AI of the European Commission as "systems that display intelligent behaviour by analysing their environment and taking actions-with some degree of autonomy-to achieve specific goals." Artificial intelligence has the potential to support guideline planning, development and adaptation, reporting, implementation, impact evaluation, certification, and appraisal of recommendations, which we will refer to as "guideline enterprise." Considering this potential, as well as the lack of guidance for the use of AI in guidelines, the Guidelines International Network (GIN) proposes a set of principles for the development and use of AI tools or processes to support the health guideline enterprise.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Drug use and acute kidney injury: a Drug-Wide Association Study (DWAS) in Denmark and Sweden.

Background: Knowledge of which medications may lead to acute kidney injury (AKI) is limited, relying mostly on spontaneous reporting in pharmacovigilance systems. We here conducted an exploratory drug-wide association study (DWAS) to screen for associations between dispensed drugs and AKI risk.

Methods: Using two large Danish and Swedish data linkages, we identified AKI hospitalizations occurring between April 1997 and December 2021 in Denmark and between March 2007 and December 2021 in Sweden.

Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update.

Since the first derivation of human pluripotent stem cells (hPSCs) 27 years ago, technologies to control their differentiation and manufacturing have advanced immensely, enabling increasing numbers of clinical trials with hPSC-derived products. Here, we revew the landscape of interventional hPSC trials worldwide, highlighting available data on clinical safety and efficacy. As of December 2024, we identify 116 clinical trials with regulatory approval, testing 83 hPSC products.

Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Hemophilia B Leyden: characteristics and natural history in the International Pediatric Network of Hemophilia Management Registry.

Background: A unique form of hemophilia B (HB) is HB Leyden. We evaluated the international Pediatric Network on Hemophilia Management Registry (PedNet) database to explore the natural history of HB Leyden, investigate genotype-phenotype associations, and guide clinical decision-making.

Objectives: To assess the association between genetic variants, endogenous factor (F)IX levels over time, treatment, and bleeding phenotype in children with HB Leyden.

Clinical Profile and Treatment Adherence in Patients with Type 2 Diabetes and Chronic Kidney Disease Who Initiate an SGLT2 Inhibitor: A Multi-cohort Study.

Introduction: The clinical landscape for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) is rapidly evolving. As part of the FOUNTAIN platform (NCT05526157; EUPAS48148), we described and compared cohorts of adult patients with CKD and T2D initiating a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before the launch of finerenone in Europe, Japan, and the United States (US).

Methods: This was a multinational, multi-cohort study of patients with T2D in five data sources: the Danish National Health Registers (DNHR) (Denmark), PHARMO Data Network (The Netherlands), Valencia Health System Integrated Database (VID) (Spain), Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex) (Japan), and Optum's de-identified Clinformatics Data Mart Database (CDM) (US).

Evidence-based guideline: premature ovarian insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI.

What Is Known Already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health.

Evidence-based guideline: Premature Ovarian Insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.

What Is Known Already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular and cognitive health.

Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction.

Background: Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.

Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies.

Association of Vascular Risk With Severe vs Non-Severe Stroke: An Analysis of the INTERSTROKE Study.

Background And Objectives: Acute stroke is associated with a spectrum of functional deficits. The objective of this analysis was to explore whether the importance of individual risk factors differ by stroke severity, which may be of relevance to public health strategies to reduce disability.

Methods: INTERSTROKE is an international case-control study of risk factors of first acute stroke (recruitment 2007-August 2015) in 32 countries.

Association between Exposure to Metals during Pregnancy, Childhood Gut Microbiome, and Risk of Intestinal Inflammation in Late Childhood.

Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease. Nonetheless, how prenatal exposure to metals eventually results in long-term effects on the gut microbiome, leading to subclinical intestinal inflammation, particularly during late childhood, has not been studied. It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation.

Atacama Large Aperture Submillimeter Telescope (AtLAST) science: The hidden circumgalactic medium.

Our knowledge of galaxy formation and evolution has incredibly progressed through multi-wavelength observational constraints of the interstellar medium (ISM) of galaxies at all cosmic epochs. However, little is known about the physical properties of the more diffuse and lower surface brightness reservoir of gas and dust that extends beyond ISM scales and fills dark matter haloes of galaxies up to their virial radii, the circumgalactic medium (CGM). New theoretical studies increasingly stress the relevance of the latter for understanding the feedback and feeding mechanisms that shape galaxies across cosmic times, whose cumulative effects leave clear imprints into the CGM.

Artificial intelligence for automatic and objective assessment of competencies in flexible bronchoscopy.

Background: Bronchoscopy is a challenging technical procedure, and assessment of competence currently relies on expert raters. Human rating is time consuming and prone to rater bias. The aim of this study was to evaluate if a bronchial segment identification system based on artificial intelligence (AI) could automatically, instantly, and objectively assess competencies in flexible bronchoscopy in a valid way.

Coronary Plaque Characteristics in Patients With Chronic Kidney Failure: Impact on Cardiovascular Events and Mortality.

Background: In patients with coronary artery disease, coronary plaques with high-risk features and low-attenuation plaque burden are independent measures associated with major adverse cardiovascular events (MACEs). Patients with chronic kidney failure may have different coronary artery disease characteristics. The aim was to assess the association of coronary plaque characteristics and coronary artery disease extent with MACE and all-cause mortality in patients with chronic kidney failure.