Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

Status in Brain Gliomas Can Be Predicted by the Spherical Mean MRI Technique.

Background And Purpose: Diffuse gliomas, a heterogeneous group of primary brain tumors, have traditionally been stratified by histology, but recent insights into their molecular features, especially the mutation status, have fundamentally changed their classification and prognosis. Current diagnostic methods, still predominantly relying on invasive biopsy, necessitate the exploration of noninvasive imaging alternatives for glioma characterization.

Materials And Methods: In this prospective study, we investigated the utility of the spherical mean technique (SMT) in predicting the status and histologic grade of adult-type diffuse gliomas.

Expression Levels of MUC5AC and MUC5B in Airway Goblet Cells Are Associated with Traits of COPD and Progression of Chronic Airflow Limitation.

Mucins 5AC (MUC5AC) and 5B (MUC5B) are the major mucins providing the organizing framework for the airway's mucus gel. We retrieved bronchial mucosal biopsies and bronchial wash (BW) samples through bronchoscopy from patients with chronic obstructive pulmonary disease ( = 38), healthy never-smokers ( = 40), and smokers with normal lung function ( = 40). The expression of MUC5AC and MUC5B was assessed immunohistochemically.

Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness.

In addition to adaptive immunity, natural killer (NK) cells of the innate immune system contribute to the control of viral infections. The HLA-E-restricted SARS-CoV-2 Nsp13232-240 epitope VMPLSAPTL renders infected cells susceptible to NK cells by preventing binding to the inhibitory receptor NKG2A. Here, we report that a recently emerged methionine to isoleucine substitution at position 2 (pM2I) of Nsp13232-240 impairs binding of the mutated epitope to HLA-E and diminishes HLA-E/peptide complex stability.

Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA.

JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.

A Small Molecule Antagonist of CX3CR1 (KAND567) Inhibited the Tumor Growth-Promoting Effect of Monocytes in Chronic Lymphocytic Leukemia (CLL).

Background/objectives: Nurse-like cells (NLCs) derived from monocytes in the tumor microenvironment support the growth of chronic lymphocytic leukemia (CLL) cells. Here, we investigated the effects of a CX3CR1 (fractalkine receptor) antagonist (KAND567) on autologous monocytes and their pro-survival effects on CLL cells in vitro.

Methods: Plasma concentration of CX3CL1 was determined by ELISA and CX3CR1 expression by flow cytometry.

Association between peripheral activated naive and double negative 2 B-cell subsets and clinical parameters in lupus nephritis patients.

Altered composition of B-cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B-cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B-cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry.

Heart failure after left atrial appendage occlusion: Insights from the LAAOS III randomized trial.

Aims: The left atrial appendage (LAA) produces natriuretic peptides and its removal or occlusion might increase the risk of heart failure (HF). We aimed to investigate the incidence of HF after LAA occlusion or removal (LAAO) in the Left Atrial Appendage Occlusion Study (LAAOS III).

Methods And Results: Patients (n = 4811) with atrial fibrillation (AF) and a CHADS-VASc score ≥2, who were having cardiac surgery for another indication, were randomized to undergo surgical LAAO or not.

Repeat Prostate Cancer Screening using Blood-based Risk Prediction or Prostate-specific Antigen in the Era of Magnetic Resonance Imaging-guided Biopsies : A Secondary Analysis of the STHLM3-MRI Randomized Clinical Trial.

Background And Objective: The use of blood-based risk prediction tools has been proposed to improve prostate cancer screening, but data on repeated screening are lacking. Our aim was to compare outcomes using the blood tests prostate-specific antigen (PSA) and Stockholm3 for repeat prostate cancer screening.

Methods: In the population-based screening-by-invitation STHLM3-MRI trial, men aged 50-74 yr were invited to participate in screening.

Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18-40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care.

Loss in Overall and Quality-Adjusted Life Expectancy for Patients With Chronic-Phase Chronic Myeloid Leukemia.

The introduction of tyrosine kinase inhibitors has considerably improved the life expectancy (LE) for patients with chronic myeloid leukemia (CML). Evaluating health-related quality of life within the treatment pathway remains crucial. Using the Swedish CML register, we included 991 adult patients with chronic-phase (CP) CML diagnosed 2007 to 2017, with follow-up until 2018.

The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understanding of their pathogeneses, which involve multiple cellular and molecular pathways. The triggering of an immune response is a common feature in neurodegenerative disorders.

Amelioration of experimental autoimmune encephalomyelitis by exogenous soluble PD-L1 is associated with restraining dendritic cell maturation and CCR7-mediated migration.

Dendritic cells (DCs) orchestrate both immune activation and immune tolerance in multiple sclerosis (MS). Manipulating the phenotypes and functions of DCs to boost their tolerogenic potential is an appealing strategy for treating MS and its animal model experimental autoimmune encephalomyelitis (EAE). Programmed cell death 1 (PD-1) delivers the immunoinhibitory signals by interacting with PD-1 ligand 1 (PD-L1), which plays a critical role in maintaining immune tolerance.

Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial.

Importance: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

Objective: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

Design, Setting, And Participants: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America.

Analysis of the Stockholm Public Health Cohort: Exploring How Ultraviolet Radiation and Other Factors Associate with Skin Cancer.

Objective: The primary aims of the study were to (1) explore the association of skin cancer and four ultraviolet radiation (UVR) indicators (sunbed use, healthcare data on diagnosed melanocytic nevi (MN) and actinic keratosis (AK), and latitude of birthplace), and (2) find factors other than UVR that could explain the increasing trend in incidence of skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and cutaneous malignant melanoma (CMM).

Methods: This population-based cohort study used self-reported questionnaire data from the Stockholm Public Health Cohort, encompassing 103 questions, merged with data from Swedish national registers. The study population included almost 35,000 Swedish-born people aged 30-66 years in 2014.

Spatial patterns of high-risk biomechanical metrics in plaques with abnormal vs. normal physiological flow indices.

Background: Plaques associated with abnormally low physiological flow reserve indices are appropriate for percutaneous coronary intervention (PCI). However, recent trials demonstrate that PCI of ischemia-producing lesions does not reduce major adverse cardiac events (MACE). Low endothelial shear stress (ESS) or high ESS gradient (ESSG) are associated with MACE wherever they occur along the plaque.

Enhancing clinical reasoning skills for medical students: a qualitative comparison of LLM-powered social robotic versus computer-based virtual patients within rheumatology.

Virtual patients (VPs) are increasingly used in medical education to train clinical reasoning (CR) skills. However, optimal VP design for enhancing interactivity and authenticity remains unclear. Novel interactive modalities, such as large language model (LLM)-enhanced social robotic VPs might increase interactivity and authenticity in CR skill practice.

Effects of structured contraceptive counseling in young women: Secondary analyses of a cluster randomized controlled trial (the LOWE trial).

Introduction: Unwanted pregnancy constitutes a huge health issue. Long-acting reversible contraception (LARC) are the most effective methods for preventing unwanted pregnancy, especially among young women. This study evaluates the intervention effect of structured contraceptive counseling on the choice, initiation, and use of LARC in young women.