Cost-Effectiveness of a Biomarker-Based Screening Strategy for Hepatocellular Carcinoma in Patients with Cirrhosis.

Introduction: Given suboptimal performance of ultrasound-based surveillance for early hepatocellular carcinoma (HCC) detection in patients with cirrhosis, there is interest in alternative surveillance strategies, including blood-based biomarkers. We aimed to evaluate the cost-effectiveness of biomarker-based surveillance in patients with cirrhosis.

Methods: We constructed a decision-analytic model to compare ultrasound/alpha-fetoprotein (AFP) and biomarker-based surveillance strategies in 1,000,000 simulated patients with compensated cirrhosis.

Serum levels of total bile acids are associated with an increased risk of HCC in patients with cirrhosis.

Background: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

Methods: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date.

Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.

The pathogenicity of PSEN2 variants is tied to Aβ production and homology to PSEN1.

Introduction: Though recognized as a potential cause of autosomal dominant Alzheimer's disease, the pathogenicity of many PSEN2 variants remains uncertain. We compared amyloid beta (Aβ) production across all missense PSEN2 variants in the AlzForum database and, when possible, to corresponding PSEN1 variants.

Methods: We expressed 74 PSEN2 variants, 21 of which had known, homologous PSEN1 pathogenic variants with the same amino acid substitution, in HEK293 cells lacking presenilin 1/2.

Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum.

The Impact of a Huge Fibroid on Pregnancy: A Case Report.

Uterine fibroids are benign smooth muscle tumors of the uterus, are relatively common in reproductive-age women, and are associated with increasing maternal age. This case study details a 37-year-old female patient who was incidentally diagnosed with a larger lower segment fibroid during her first pregnancy scan and responded well to treatment, delivered by a cesarian due to transverse lie and lower uterine segment fibroid completely obstructing the birth canal.

Sex-Specific Vulnerabilities to Subclinical Vascular Brain Injury in Early Late-Life: The Framingham Heart Study.

Objective: Subclinical vascular brain injury is an increasingly recognized risk factor for stroke and dementia. Despite well-established sex differences in vascular risk and disease prevalence, the impact of sex on drivers of subclinical vascular brain injury remains unclear, presenting a barrier to developing sex-specific prevention guidelines. We aimed to establish the extent to which sex moderates associations between vascular risk factors and magnetic resonance imaging (MRI) measures of subclinical brain injury in stroke-free older adults.

Generative Artificial Intelligence for Health Technology Assessment: Opportunities, Challenges, and Policy Considerations: An ISPOR Working Group Report.

Objectives: To provide an introduction to the uses of generative artificial intelligence (AI) and foundation models, including large language models, in the field of health technology assessment (HTA).

Methods: We reviewed applications of generative AI in 3 areas: systematic literature reviews, real-world evidence, and health economic modeling.

Results: (1) Literature reviews: generative AI has the potential to assist in automating aspects of systematic literature reviews by proposing search terms, screening abstracts, extracting data, and generating code for meta-analyses; (2) real-world evidence: generative AI can facilitate automating processes and analyze large collections of real-world data, including unstructured clinical notes and imaging; (3) health economic modeling: generative AI can aid in the development of health economic models, from conceptualization to validation.

A needs assessment of hospital management and leadership training among Indian medical undergraduates.

Background: Medical undergraduate students are often unaware of the managerial aspects of operating a healthcare facility. This leads to confusion and a sense of being lost when they assume administrative roles, highlighting the need for hospital management and leadership training. This prompted us to evaluate the needs of medical undergraduates concerning these crucial aspects.

ATN blood biomarkers are related to digital cognitive assessment in type 1 diabetes.

Introduction: Associations between amyloid-tau-neurodegeneration (ATN) plasma biomarkers and cognition have not been characterized in adults with type 1 diabetes (T1D).

Methods: Using data from participants in the Glycemic Variability and Fluctuations in Cognitive Status in Adults with T1D (GluCog) study ( = 114), we evaluated associations between phosphorylated tau (pTau)181, pTau217, β-amyloid 42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) and self-administered digital cognitive tests, adjusting for age, sex, education, comorbidities (e.g.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

Introduction: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations.

Methods: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.

15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN.

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (), presenilin 1 (), or presenilin 2 () genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset.

Ubiquitin-Proteasome System in the Different Stages of Dominantly Inherited Alzheimer's Disease.

This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating (CDR). Using the SOMAscan assay, we detected subtle increases in specific ubiquitin enzymes associated with proteostasis in mutation carriers (MCs) up to two decades before the estimated symptom onset. This was followed by more pronounced elevations of UPS-activating enzymes, including E2 and E3 proteins, and ubiquitin-related modifiers.

Amyloid beta-independent sleep markers associated with early regional tau burden and cortical thinning.

Introduction: Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD.

Methods: Thirty-nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at-home polysomnography as well as tau positron emission tomography (flortaucipir-PET), amyloid PET (Pittsburgh compound B [PiB]-PET), and magnetic resonance imaging-derived assessment of cortical thickness (CT).

γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).

Background: Genetic variants that cause autosomal dominant Alzheimer's disease are highly penetrant but vary substantially regarding age at symptom onset (AAO), rates of cognitive decline, and biomarker changes. Most pathogenic variants that cause autosomal dominant Alzheimer's disease are in presenilin 1 (PSEN1), which encodes the catalytic core of γ-secretase, an enzyme complex that is crucial in production of amyloid β. We aimed to investigate whether the heterogeneity in AAO and biomarker trajectories in carriers of PSEN1 pathogenic variants could be predicted on the basis of the effects of individual PSEN1 variants on γ-secretase activity and amyloid β production.

Left Frontoparietal Control Network Connectivity Moderates the Effect of Amyloid on Cognitive Decline in Preclinical Alzheimer's Disease: The A4 Study.

Background: Stronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer's disease related pathology and neurodegeneration in smaller cohort studies.

Objectives: We investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).

Design: Longitudinal mixed.

Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease.

Background: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH).

Objectives: 1) To assess the relationship between baseline WMH volume and baseline MCH.

Health disparities in cervical cancer: Estimating geographic variations of disease burden and association with key socioeconomic and demographic factors in the US.

Background: Despite advances in cervical cancer (CC) prevention, detection, and treatment in the US, health disparities persist, disproportionately affecting underserved populations or regions. This study analyzes the geographical distribution of both CC and recurrent/metastatic CC (r/mCC) in the US and explores potential risk factors of higher disease burden to inform potential strategies to address disparities in CC and r/mCC.

Methods: We estimated CC screening rates, as well as CC burden (number of patients with CC diagnosis per 100,000 eligible enrollees) and r/mCC burden (proportion of CC patients receiving systemic therapy not in conjunction with surgery or radiation), at the geographic level between 2017-2022 using administrative claims.