Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models - Of mice and men.

Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties.

PCSK9 inhibitor experiences and preferences of patients and healthcare professionals in decision-making: A mixed methods study.

Background And Aims: This study investigated how patients experience and which outcomes matter to patients and healthcare professionals in the decision to initiate proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) as add-on lipid-lowering treatment (LLT).

Methods: We performed a mixed methods study: very high-risk patients qualifying for PCSK9i reimbursement were interviewed about their experiences and preferences. Subsequently, patients using PCSK9i completed an anonymous online survey about their experiences.

The effect between metabolic syndrome and life expectancy after cancer diagnosis: Catalan cohort study.

This study examines remaining life expectancy (RLE) after a cancer diagnosis, focusing on age, sex, cancer type, and metabolic syndrome (MS) components, using data from the SIDIAP database in Catalonia (2006-2017). RLE was analyzed for 13 cancer types, stratified by sex and MS components. The cohort study includes 183,364 individuals followed from diagnosis until death, transfer, or study end (December 2017).

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Discovery of Methylated DNA Biomarkers for Potential Non-Endoscopic Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

Background And Aims: We sought to develop a minimally-invasive, robust, accessible nonendoscopic strategy to diagnose Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and its immediate precursor lesion, high-grade dysplasia (HGD) based on methylated DNA biomarkers applied to a retrievable sponge-capsule device in a cohort representative of the BE population (i.e., mostly short-segment, non-dysplastic BE, NDBE).

Reliability of various Antimicrobial Susceptibility Testing Methods for Piperacillin/tazobactam in challenging Escherichia coli isolates.

Piperacillin/tazobactam antimicrobial susceptibility testing (AST) against Enterobacterales can be challenging. The aim of this study was to assess the reproducibility of various automated (Vitek®2) and non-automated AST methods (broth microdilution (BMD), minimum inhibitory concentration (MIC) test strip, and disk diffusion) for piperacillin/tazobactam in 'challenging' E. coli isolates.

The Long-Term Effect of Childhood Otitis Media on Speech-in-Noise Testing at Ages 9 and 13.

Objective: To investigate the relationship between a history of otitis media (OM) in early childhood and speech reception thresholds (SRT) in later childhood, using the Dutch digits-in-noise (DIN) test at ages 9 and 13 years.

Methods: This study was conducted within the Generation R study, a prospective birth cohort in Rotterdam, the Netherlands. Children underwent pure-tone audiometry and DIN testing at ages 9 (2011-2015) and 13 (2016-2020) years.

Implementation of model-informed precision dosing for tamoxifen therapy in patients with breast cancer: A prospective intervention study.

Tamoxifen is an estrogen-receptor (ER) antagonist, used as adjuvant treatment of ER-positive breast cancer. It is converted by CYP2D6 into endoxifen, its most active metabolite. Patients with endoxifen plasma concentrations <16 nM face a higher risk of recurrence.

Long-term survival of participants in the PASART-1 and PASART-2 trials of neo-adjuvant pazopanib and radiotherapy in soft tissue sarcoma.

Objective: This study aims to assess the long-term safety and efficacy of adding pazopanib to neo-adjuvant radiotherapy followed by surgery in patients with high-risk non-metastatic soft tissue sarcoma of the trunk and extremities treated in the PASART-1 and PASART-2 trials, as well as to compare the PASART cohorts to a control cohort receiving standard treatment during the same time period from the Netherlands Cancer Registry (IKNL) to investigate if adding pazopanib improves Overall Survival (OS).

Methods: Updated follow-up data on disease control, survival and long-term toxicities of the PASART-trials were extracted from electronic patient records. The effect of adding pazopanib to neo-adjuvant radiotherapy on OS was investigated by comparing the combined PASART cohorts to the IKNL cohort via direct comparison and exact matching analysis.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.

Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.

Esophageal Candida Infection and Esophageal Cancer Risk in Patients With Achalasia.

Importance: Patients with achalasia face a higher risk of developing esophageal cancer (EC), but the surveillance strategies for these patients remain controversial due to the long disease duration and the lack of identified risk factors.

Objective: To investigate the prevalence of esophageal Candida infection among patients with achalasia and to assess the association of Candida infection with EC risk within this population.

Design, Setting, And Participants: This retrospective cohort study included patients with achalasia diagnosed at or referred for treatment and monitoring to the Erasmus University Medical Center in Rotterdam, the Netherlands, between January 1, 1980, and May 31, 2024.

Adverse health outcomes and health-related quality of life (HRQoL) among long-term adolescent and young adult (AYA) brain tumour survivors: results from the population-based SURVAYA study.

Purpose: Adolescent and young adult (AYA) malignant brain tumour (BT) survivors are at risk of adverse health outcomes, which may impact their health-related quality of life (HRQoL). This study aimed to investigate the (1) prevalence of physical and psychological adverse health outcomes, (2) the HRQoL, and (3) the association of adverse health outcomes and HRQoL among long-term AYA-BT survivors. Adverse health outcomes and HRQoL were compared to other AYA cancer (AYAC) survivors.

Monounsaturated fatty acids from plant or animal sources and risk of type 2 diabetes in three large prospective cohorts of men and women.

Aims/hypothesis: Existing evidence on the relationship between intake of monounsaturated fatty acids (MUFAs) and type 2 diabetes is conflicting. Few studies have examined whether MUFAs from plant or animal sources (MUFA-Ps and MUFA-As, respectively) exhibit differential associations with type 2 diabetes. We examined associations of intakes of total MUFAs, MUFA-Ps and MUFA-As with type 2 diabetes risk.

Retroperitoneal Soft Tissue Sarcoma and Kidney Autotransplantation: A Case Report.

Soft tissue sarcomas (STSs) are rare malignancies, with retroperitoneal soft tissue sarcoma (RPS) constituting 10%-15% of all STSs. RPS often presents late due to minimal early symptoms, typically requiring complete en-bloc resection for optimal survival outcomes. Achieving radical resection can be challenging due to the tumor's proximity to vital organs.

Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients.

Traditional classification by clinical phenotype or oxidative phosphorylation (OXPHOS) complex deficiencies often fails to clarify complex genotype-phenotype correlations in mitochondrial disease. A multimodal functional assessment may better reveal underlying disease patterns. Using imaging flow cytometry (IFC), we evaluated mitochondrial fragmentation, swelling, membrane potential, reactive oxygen species (ROS) production, and mitochondrial mass in fibroblasts from 31 mitochondrial disease patients.

Impact of Additional Active Treatment for Prostate Cancer on Health-related Quality of Life of Men: Results from the EUPROMS 2.0 1-year Follow-up Survey.

Background And Objective: In 2019 and 2021, Europa Uomo initiated the Europa Uomo Patient Reported Outcome Study (EUPROMS) and the EUPROMS 2.0 survey, with the goal of collecting data on patients' self-reported perspective on physical and mental well-being outside of a clinical trial setting, to be able to investigate the burden of prostate cancer (PCa) treatment from a patient-to-patient perspective. Acknowledging the importance of collecting quality of life (QoL) follow-up data, a 1-yr follow-up (1yrFU) study was conducted to assess the effect of additional PCa treatment on QoL.

How to Put Survival After Cardiothoracic Interventions in the General Population Context: A Case-Based Practical Guideline to Calculate Cumulative Matched-General-Population Survival.

Background: Observed patient survival after cardiothoracic interventions should ideally be placed in the context of matched-general-population survival. This study outlines several methodologies of matching general population mortality to the study sample, subsequently calculating cumulative matched-general-population survival, highlighting their respective advantages, disadvantages, and limitations.

Methods: A multicenter data set containing survival data after the Ross procedure was used for methodological illustration.

Medication use is associated with distinct microbial features in anxiety and depression.

This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing (16S) and shallow shotgun sequencing (WGS) were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and Neurocomputational Mechanisms of Affiliation and Personality Study Center for Biomedical Research Excellence (NeuroMAP CoBRE) cohorts.

A new guide for basic psychological support for persons affected by neglected tropical diseases: A peer support tool suitable for persons with a diagnosis of leprosy and lymphatic filariasis.

Background: People with disabilities due to neglected tropical diseases (NTDs), such as leprosy and lymphatic filariasis (LF), often encounter situations of stigma and discrimination that significantly impact their mental wellbeing. Mental wellbeing services are often not available at the peripheral level in NTD-endemic countries, and there is a need for such services. Basic psychological support for persons with NTDs (BPS-N) from peers is an important potential solution for addressing mental wellbeing problems.

Injection Techniques for Filler Procedures With Illustration: Narrative Review.

This narrative review explores the various injection techniques utilized in facial filler procedures, emphasizing their applications, benefits, and potential complications. The increasing demand for total facial contouring and rejuvenation has led to a rise in the use of volumizing fillers and the integration of these procedures with other treatments such as toxins, threads, lasers, radiofrequency, and ultrasound. Achieving satisfactory results necessitates a comprehensive understanding of facial anatomy and the effects of aging on skin tissue.