Differential effects of volanesorsen on apoC-III, triglycerides and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or non-genetic criteria.

Background: Familial chylomicronemia syndrome (FCS) is diagnosed by genetic or non-genetic criteria.

Objective: To assess responses to treatment of apolipoprotein (apo)C-III, triglycerides, and pancreatitis events in patients with FCS-based diagnostic methods.

Methods: APPROACH enrolled 66 patients with FCS randomized to volanesorsen or placebo for 12 months.

Effects of aortic valve calcification on transcatheter aortic valve replacement for low-flow, low-gradient aortic stenosis.

Background: Patients with low-flow, low-gradient (LFLG) aortic stenosis (AS) have precarious hemodynamics and are a fragile population for intervention. Quantification of aortic valve calcification (AVC) severity is a critical component of the evaluation for transcatheter aortic valve replacement (TAVR); this study aims to further clarify its utility for risk stratification in LFLG AS.

Methods: This retrospective study evaluated 467 patients with LFLG AS undergoing TAVR at a large quaternary-care hospital from January 2019 to December 2021.

Association between symptom characteristics and disease severity in patients suspected of coronary artery disease.

Background: Discrepancies often exist between patient-reported symptoms and diagnostic test findings in patients with suspected obstructive coronary artery disease (CAD).

Objectives: To quantify the association between patient-reported symptoms and the diagnosis of severe stenosis in patients with suspected obstructive CAD.

Methods: Two large-scale cohorts of patients with new-onset symptoms suggestive of obstructive CAD were evaluated.

How climate change is shaping young people's health: a participatory, youth co-led study from Bangladesh, Guatemala and Nigeria.

Introduction: Climate change is shaping adolescent and young people's (AYP) transitions to adulthood with significant and often compounding effects on their physical and mental health. The climate crisis is an intergenerational inequity, with the current generation of young people exposed to more climate events over their lifetime than any previous one. Despite this injustice, research and policy to date lacks AYP's perspectives and active engagement.

Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries.

Objective: The emergence of resistance-associated substitutions (RASs) poses a significant challenge to the effective treatment of hepatitis C virus (HCV) infection using direct-acting antivirals. This study's objective was to observe the prevalence of HCV genotypes and RAS within the Former Soviet Union (FSU) countries.

Methods: We analysed 60 NS3, 313 NS5A and 1119 NS5B sequences of HCV deposited in open-access databases from 11 FSU countries for the prevalence of genotypes and the presence of RAS using the Geno2Pheno software.

Oncocytoma: a rare neoplasm of the caruncle.

Oncocytoma is a rare benign neoplasm of the glandular tissue, most commonly found in the caruncle of the eye. These lesions have an excellent prognosis and have not been reported to recur after resection from the caruncle. Given the wide range of differentials and potential for malignancy, excision and histopathological examination are recommended to establish the diagnosis and guide proper treatment.

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations.

The mitochondrial choline transporter, SLC25A48, regulates urine and blood choline levels in humans.

Choline is an essential nutrient for the biosynthesis of phospholipids and neurotransmitters and controls several physiological functions in mammals. It is metabolized in the organelles within cells, including mitochondria. However, its subcellular distribution and mode of mitochondrial transport remain poorly understood.

Comparative effectiveness of antipsychotic treatment strategies for relapse prevention in first-episode schizophrenia in Finland: a population-based cohort study.

Background: The best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia are unclear. We aimed to assess different treatment strategies used before and after the first relapse, and their associations with subsequent relapse risk.

Methods: In this population-based cohort study, we enrolled individuals (aged ≤45 years) with first-episode schizophrenia who were hospitalised and subsequently relapsed between 1996 and 2014 from the nationwide Finnish Hospital Discharge Register.

High-resolution analysis of human centromeric chromatin.

Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays.

The blood transcriptional response in patients developing intensive care unit-acquired pneumonia.

Introduction: Immune response dysregulation has been implicated in the development of intensive care unit (ICU)-acquired pneumonia. We aimed to determine differences in the longitudinal blood transcriptional response between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls).

Methods: We performed a case-cohort study in mechanically ventilated trauma and surgery patients with ICU stays >2 days, enrolled in 30 hospitals across Europe.

B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells.

Background: Chordoma is a slow-growing, primary malignant bone tumor that arises from notochordal tissue in the midline of the axial skeleton. Surgical excision with negative margins is the mainstay of treatment, but high local recurrence rates are reported even with negative margins. High-dose radiation therapy (RT), such as with proton or carbon ions, has been used as an alternative to surgery, but late local failure remains a problem.

Stratification system with dual human endogenous retroviruses for predicting immunotherapy efficacy in metastatic clear-cell renal cell carcinoma.

Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.

Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial.

Leveraging mRNA technology for antigen based immuno-oncology therapies.

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response.

Metabolic dysfunction-associated steatotic liver disease in children.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively.

Temperature and myocardial infarction among migrants in Kuwait.

Background: Kuwait, one of the world's hottest countries, faces increasing temperatures due to climate change. With a large migrant population predominantly employed in physically demanding jobs, the exact effects and burdens of temperature exposure on cardiovascular risk among this population remain unknown. This study aimed to investigate the relationship between temperature and myocardial infarction (MI) risk among migrants in Kuwait.

Cardiovascular disease and bipolar disorder: A review of pathophysiology and treatment implications.

Objective: Despite the well-established increased risk of cardiovascular mortality in individuals with bipolar disorder (BD), prevention and treatment of cardiovascular risk factors and diseases have been largely overlooked in this population. This manuscript reviews the pathophysiological basis of the connection between BD and cardiovascular diseases, highlighting their shared mechanisms, reciprocal interactions, and relevant prevention and treatment strategies.

Methods: For this narrative review, a search was carried out on PubMed using the keywords bipolar disorder, cardiovascular diseases, and cardiovascular risk factors.

Applying implementation science frameworks to understand why fisherfolk continue or discontinue pre-exposure prophylaxis for HIV prevention in Uganda: a qualitative analysis.

Introduction: In Uganda, fisherfolk have an HIV prevalence between 15% and 40%, significantly higher than the national average of 5.5%. Pre-exposure prophylaxis (PrEP) is effective in preventing HIV but faces challenges in uptake and continuation among fisherfolk.

How Do Clinicians Use Quotations in Goals of Care Notes?

Background: Quoting patients in electronic medical record (EMR) notes is controversial. Quotations may be used to promote accuracy in documentation. However they also may be used to cast skepticism on patient speech.

Long-term Mental Health Morbidity in Adult Survivors of COVID-19 Critical Illness - A Population-based Cohort Study.

Background: Survivorship after coronavirus disease 2019 (COVID-19) critical illness may be associated with important long-term sequelae, but little is known regarding mental health outcomes.

Research Question: What is the association between COVID-19 critical illness and new post-discharge mental health diagnoses.

Study Design: AND METHODS: We conducted a population-based cohort study in Ontario, Canada (January 1, 2020-March 31, 2022).

Impact of cuproptosis in gliomas pathogenesis with targeting options.

Gliomas constitute the most prevalent primary central nervous system tumors, often characterized by complex metabolic profile, genomic instability, and aggressiveness, leading to frequent relapse and high mortality rates. Traditional treatments are commonly ineffective because of gliomas increased heterogeneity, invasive characteristics and resistance to chemotherapy. Among several pathways affecting cellular homeostasis, cuproptosis has recently emerged as a novel type of programmed cell death, triggered by accumulation of copper ions.