The Cost-Effectiveness of CDK4/6 Inhibitors in Treating HR+/HER2- Metastatic Breast Cancer Patients in the USA: When Non-medication Expenses are Considered.

Background And Objective: Cyclin-dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy (ET) significantly enhance progression-free survival and overall survival in patients diagnosed with HR+/HER2- metastatic breast cancer (MBC). However, they are highly expensive, and their economic impact has not been fully evaluated. This is a retrospective secondary analysis evaluating the cost effectiveness of these drugs, differentiating between medication-related and non-medication costs from a healthcare perspective.

The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response.

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment.

Digital Solutions for the Optimization of Pharmacologic Therapy for Heart Failure.

Data from large-scale, randomized, controlled trials demonstrate that contemporary treatments for heart failure (HF) can substantially improve morbidity and mortality. Despite this, observed outcomes for patients living with HF are poor, and they have not improved over time. The are many potential reasons for this important problem, but inadequate use of optimal medical therapy for patients with HF, an important component of guideline-directed medical therapy, in routine practice is a principal and modifiable contributor.

CAR/CSACI Practice Guidance for Contrast Media Hypersensitivity.

Contrast media, including iodinated contrast media and gadolinium-based contrast agents, are commonly administered pharmaceuticals with excellent safety profiles. However, a minority of the population may experience a hypersensitivity reaction following intravenous administration. Hypersensitivity reactions can be immediate or delayed, and range from mild, such as urticaria, to severe, including anaphylaxis.

Optimising fatigue, abdominal pain and faecal incontinence in people with inflammatory bowel disease (IBD-BOOST Optimise): feasibility study of a checklist and algorithm for initial nurse-led management.

Objective: Many people with inflammatory bowel disease (IBD) experience fatigue, pain and faecal incontinence that some feel are inadequately addressed. It is unknown how many have potentially reversible medical issues underlying these symptoms.

Methods: We conducted a study testing the feasibility of a patient-reported symptom checklist and nurse-administered management algorithm ('Optimise') to manage common medical causes of IBD-related fatigue, pain and faecal incontinence.

Integrating Model-Informed Drug Development With AI: A Synergistic Approach to Accelerating Pharmaceutical Innovation.

The pharmaceutical industry constantly strives to improve drug development processes to reduce costs, increase efficiencies, and enhance therapeutic outcomes for patients. Model-Informed Drug Development (MIDD) uses mathematical models to simulate intricate processes involved in drug absorption, distribution, metabolism, and excretion, as well as pharmacokinetics and pharmacodynamics. Artificial intelligence (AI), encompassing techniques such as machine learning, deep learning, and Generative AI, offers powerful tools and algorithms to efficiently identify meaningful patterns, correlations, and drug-target interactions from big data, enabling more accurate predictions and novel hypothesis generation.

Predicting Heart Rate at the Anaerobic Threshold Using a Machine Learning Model Based on a Large-Scale Population Dataset.

For effective exercise prescription for patients with cardiovascular disease, it is important to determine the target heart rate at the level of the anaerobic threshold (AT-HR). The AT-HR is mainly determined by cardiopulmonary exercise testing (CPET). The aim of this study is to develop a machine learning (ML) model to predict the AT-HR solely from non-exercise clinical features.

Infant Passive Protection Against Coronavirus Through Exclusive Breastfeeding: A Cross-Sectional Study.

Background/objectives: This study aimed to determine the percentage and duration of neutralizing antibodies against the Omicron variant in human milk after vaccination against SARS-CoV-2, considering the three different vaccine technologies approved in Brazil.

Methods: A cross-sectional study was conducted with lactating women who received the complete vaccination cycle with available vaccines (AstraZeneca, Pfizer, CoronaVac, and Janssen). The participants resided in Rio de Janeiro, and samples were collected from April to October 2022.

The Association of Dining Companionship with Energy and Nutrient Intake Among Community-Dwelling Japanese Older Adults.

Background: Community-dwelling older adults are at risk of malnutrition due to age-related declines in energy and nutrient intake. While the positive effect of dining companions on energy and nutrient intake has been suggested, evidence remains inconclusive. This study investigated the association between the number of dining companions and energy and nutrient intake, as well as the contribution of specific food groups to higher intake in the presence of dining companions.

Prevalence and functional impact of chronotropic incompetence in amyloid cardiomyopathy: a multicentre analysis.

Background: Little evidence is available about heart rate (HR) response to exercise as well as its relationship with functional capacity in amyloid cardiomyopathy. Then, in a multicentre cohort of patients with amyloid cardiomyopathy, we investigated the prevalence of chronotropic incompetence (CI) and its relationships with cardiopulmonary exercise testing (CPET) variables.

Methods: Data from 172 outpatients with amyloid cardiomyopathy who performed a maximal CPET and who had no significant rhythm disorders were analysed.

Withdrawal of antitumour necrosis factor in inflammatory bowel disease patients in remission: a randomised placebo-controlled clinical trial of GETECCU.

Background And Objectives: Primary objectives: to compare the rates of sustained clinical remission at 12 months in patients treated with antitumour necrosis factor (anti-TNF) and immunomodulators who withdraw anti-TNF treatment versus those who maintain it.

Secondary Objectives: to evaluate the effect of anti-TNF withdrawal on relapse-free time, endoscopic and radiological activity, safety, quality of life and work productivity; and to identify predictive factors for relapse.

Design: Prospective, quadruple-blind, multicentre, randomised, controlled trial.

Expert consensus on the benefits of neuraminidase in conventional influenza vaccines: a Delphi study.

Background: Seasonal vaccination is the mainstay of human influenza prevention. Licensed influenza vaccines are regularly updated to account for viral mutations and antigenic drift and are standardised for their haemagglutinin content. However, vaccine effectiveness remains suboptimal.

BiomiX, a user-friendly bioinformatic tool for democratized analysis and integration of multiomics data.

Background: Interpreting biological system changes requires interpreting vast amounts of multi-omics data. While user-friendly tools exist for single-omics analysis, integrating multiple omics still requires bioinformatics expertise, limiting accessibility for the broader scientific community.

Results: BiomiX tackles the bottleneck in high-throughput omics data analysis, enabling efficient and integrated analysis of multiomics data obtained from two cohorts.

Risk Factors for Mortality Among Older Adults with Hospital-Acquired Bloodstream Infections in the Intensive Care Unit: A Multicenter Cohort Study.

Introduction: We aimed to investigate risk factors for mortality among older adults (≥ 75 years) with hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU).

Methods: We included patients aged ≥ 75 years with HA-BSI in ICU from the EUROBACT-2 cohort (2019-2021). Univariable and multivariable analyses were conducted to identify predictors of 28-day mortality.

AI image analysis as the basis for risk-stratified screening.

Artificial intelligence (AI) has emerged as a transformative tool in breast cancer screening, with two distinct applications: computer-aided cancer detection (CAD) and risk prediction. While AI CAD systems are slowly finding its way into clinical practice to assist radiologists or make independent reads, this review focuses on AI risk models, which aim to predict a patient's likelihood of being diagnosed with breast cancer within a few years after negative screening. Unlike AI CAD systems, AI risk models are mainly explored in research settings without widespread clinical adoption.

Outcomes in patients with acute myeloid leukemia older than 70 years within the last 30 years, a single center experience.

As median age of patients with acute myeloid leukemia is 72 years, older patients continue to be a vulnerable cohort representing significant challenges in clinical practice. Patient-specific comorbidities as well as leukemia-specific unfavorable molecular- and cytogenetics confer even poorer outcomes. Treatment of AML therefore needs to be less toxic to prevent harm while lowering or eradicating leukemic burden to prolong survival.

Staging of prostate Cancer with ultra-fast PSMA-PET scans enhanced by AI.

Purpose: PSMA-PET is a reference standard examination for patients with prostate cancer, but even using recently introduced digital PET detectors image acquisition with standard field-of-view scanners is still in the range of 20 min. This may cause limited access to examination slots because of the growing demand for PSMA-PET. Ultra-fast PSMA-PET may enhance throughput but comes at the cost of poor image quality.

Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology.

Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. Molecular analyses resulted in a median number of 2.

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial.

We conducted a phase I trial to determine the optimal dose of triplet therapy with the tyrosine kinase inhibitor sitravatinib plus nivolumab plus ipilimumab in 22 previously untreated patients with advanced clear cell renal cell carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), 1-year survival probability, and sitravatinib pharmacokinetics.

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.

Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats.

The COVID-19 pandemic exposed a global deficiency of systematic, data-driven guidance to identify high-risk individuals. Here, we illustrate the utility of routinely recorded medical history to predict the risk for 1741 diseases across clinical specialties and support the rapid response to emerging health threats such as COVID-19. We developed a neural network to learn from health records of 502,489 UK Biobank participants.

Construct validity and responsiveness of ASAS Health Index assessed in two longitudinal studies of tumour necrosis factor alpha inhibitor initiation and dose reduction in patients with axial spondyloarthritis.

Background: The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a novel questionnaire of global functioning for patients with axial spondyloarthritis (SpA).

Objective: The objective was to assess the construct validity, discriminatory ability and responsiveness of ASAS HI in relation to patient-reported outcome measures (PROMs), MRI and radiography.

Methods: Data from two longitudinal studies with tumour necrosis factor inhibitor (TNFi) initiation (novel MRI And biomarkers in Golimumab-treated patients with axial spondyloarthritis (MANGO): n=45) respectively tapering (Dose adjustment of Biological treatment in patients with SpA (DOBIS): n=106) were used.

Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study.

Introduction: Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving.

Materials And Methods: This is a retrospective analysis of a prospectively collected population-based registry.