Single-cell DNA sequencing reveals pervasive positive selection throughout preleukemic evolution.

The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees.

Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA.

Background: Diffuse pleural mesothelioma (dPM) is an aggressive malignancy, primarily treated with palliative systemic therapy. Since 2022, nivolumab-ipilimumab (nivo/ipi) has replaced chemotherapy as the standard first-line treatment for dPM in the Netherlands. Chemotherapy remains a rational second-line treatment.

Coronary Computed Tomography Angiography in Heart Transplant Patients: Current Insights and Future Directions.

Cardiac allograft vasculopathy (CAV) remains a significant challenge after heart transplantation, necessitating effective surveillance methods. This review centers around the role of coronary computed tomography angiography (CCTA) in CAV surveillance, given its unique capabilities to visualize and quantify CAV in comparison with other imaging modalities, including invasive coronary angiography and intravascular ultrasound. CCTA has shown good diagnostic performance for detecting and monitoring CAV, exemplified by a higher sensitivity and negative predictive value compared with invasive coronary angiography.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Current practices in prevention, screening, and treatment of diabetes in kidney transplant recipients: European survey highlights from the ERA DESCARTES Working Group.

Background: Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

Methods: The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Results: Answers were obtained from 121/241 transplant centres (50%) across 15 European countries.

Nurse-Led Self-Management Support After Organ Transplantation - A Multicenter, Stepped-Wedge Randomized Controlled Trial.

Unlabelled: In this unblinded multi-center stepped-wedge randomized controlled trial the effectiveness of the nurse-led ZENN-intervention was tested in promoting self-management skills in comparison to standard care among heart, lung and kidney transplant recipients. This intervention is based on behaviour change theories and was conducted in four sessions over 6 months at the outpatient clinic. The experimental group received standard care, plus the ZENN-intervention, while the control group received only standard care.

Expanding the Scope of Microvascular Inflammation: Unveiling Its Presence Beyond Antibody-Mediated Rejection Into T-Cell Mediated Contexts.

Microvascular inflammation (MVI) in kidney transplant biopsies is mainly associated with antibody-mediated rejection (AMR), sparking debate within the Banff Classification of Renal Allograft Pathology regarding its exclusivity. This study reviewed the literature on MVI in T cell-mediated rejection (TCMR) and analyzed MVI in our transplant population. We searched English publications in MEDLINE, Embase, Web of Science, Cochrane, and Google Scholar until June 2024, focusing on glomerulitis (g), peritubular capillaritis (ptc), or MVI in kidney transplant biopsies classified as TCMR.

Impact of a national HPV vaccination programme for preadolescent girls on cytology screening performance and CIN2+ incidence: five-year population-based cervical screening results from Slovenia.

Background: HPV vaccination is most efficacious in preventing cervical cancer and its precursors when administered during preadolescence. Because in Slovenia women are invited for cytology screening from age 20, women targeted for preadolescent HPV vaccination have been screening-eligible since 2018. We aim to assess the impact of preadolescent HPV vaccination programme on cytology screening performance and CIN2+ incidence.

Association between gut microbiome profiles and host metabolic health across the life course: a population-based study.

Background: The human gut microbiome changes considerably over time. Previous studies have shown that gut microbiome profiles correlate with multiple metabolic traits. As disease development is likely a lifelong process, evidence gathered at different life stages would help gain a better understanding of this correlation.

International expert consensus on micronutrient supplement use during the early life course.

Background: Growing evidence demonstrates that maternal nutrition is crucial for the health of the mother-to-be, and early life course of the offspring. However, for most micronutrients, guidelines are inconsistent. This Delphi study aimed to investigate the level of expert consensus on maternal nutrition and micronutrient needs during preconception, pregnancy and lactation.

Unloader brace or high tibial osteotomy in the treatment of the young patient with medial knee osteoarthritis: a randomized controlled trial.

Background And Purpose:  For medial knee osteoarthritis (OA), operative and nonoperative treatment options are available. Two widely applied unloading therapies are a valgus unloader brace and a high tibial osteotomy (HTO). We aimed to compare the effects of a valgus unloader knee brace with an HTO on knee pain after 1 year in patients with symptomatic medial knee OA.

A case of lipoprotein glomerulopathy due to the pathogenic APOE Las Vegas variant c.509C>A: p. (Ala170Asp).

This report describes a rare case of lipoprotein glomerulopathy. A 63 year-old man presented with nephrotic syndrome unresponsive to rituximab and tacrolimus. Blood tests showed a mild- to moderate hypertriglyceridemia suggesting familial dysbetalipoproteinemia (FD).

Psychological health status after major trauma across different levels of trauma care: A multicentre secondary analysis.

Introduction: Concentration of trauma care in trauma network has resulted in different trauma populations across designated levels of trauma care.

Objective: Describing psychological health status, by means of the impact event scale (IES) and the hospital anxiety and depression scale (HADS), of major trauma patients one and two years post-trauma across different levels of trauma care in trauma networks.

Methods: A multicentre retrospective cohort study was conducted.

HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design.

Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation.

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.

Recurrent glioblastoma in national guidelines on the diagnosis and treatment of gliomas: A matter of European practice variation.

Introduction: The optimal treatment for recurrent glioblastoma patients remains not well-defined in international guidelines. On top of that, the availability of national guidelines is uncharted.

Research Question: This study aimed to investigate the availability of national guidelines on the diagnosis and treatment of adult glioma throughout Europe, specifically focusing on recurrent glioblastoma.

Personalized Dynamic Prediction Model for Biopsy Timing in Patients With Prostate Cancer During Active Surveillance.

Importance: Active surveillance (AS) for patients with prostate cancer (PC) often includes fixed repeat prostate biopsies that do not account for the varying risk of reclassification to significant disease. Given the invasive nature and potential complications of biopsies, a personalized approach is needed to balance the burden of biopsies with the risk of missing disease progression.

Objective: To develop and externally validate a dynamic model that predicts an individual's risk of PC reclassification during AS.

Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs.

Treatment options for the bleeding disorder von Willebrand disease type 2B (VWD2B) are insufficient and fail to address the negative effects of circulating mutant von Willebrand factor (VWF). The dominant-negative nature of VWD2B makes functionally defective VWF an interesting therapeutic target. Previous in vitro studies have demonstrated the feasibility of allele-selective silencing of mutant VWF using small interfering RNAs (siRNAs) targeting common single nucleotide polymorphisms (SNPs) in the human VWF gene, an approach that can be applied irrespective of the disease-causing VWF mutation.

Longitudinal cardiac imaging for assessment of myocardial injury in non-hospitalised community-dwelling individuals after COVID-19 infection: the Rotterdam Study.

Background: The aim of this study was to assess the presence of myocardial injury after COVID-19 infection and to evaluate the relation between persistent cardiac symptoms after COVID-19 and myocardial function in participants with known cardiovascular health status before infection.

Methods: In the prospective population-based Rotterdam Study cohort, echocardiography and cardiovascular magnetic resonance (CMR) were performed among participants who recovered from COVID-19 at home within 2 years prior to inclusion in the current study. Persistent cardiac symptoms comprised only self-reported symptoms of chest pain, dyspnoea or palpitations lasting >4 weeks after COVID-19 infection.

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.

New Potent Inhibitor of Transforming Growth Factor-Beta (TGFβ) Signaling that is Efficacious against Microsatellite Stable Colorectal Cancer Metastasis in Combination with Immune Checkpoint Therapy in Mice.

Blockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile.

Newborn With Refractory Seizures Due To Hemimegalencephaly And Tuberous Sclerosis Complex: Case Report and Literature Review.

Background Hemimegalencephaly (HME) is a rare congenital disorder that is initiated during embryonic development with abnormal growth of one hemisphere. Tuberous sclerosis complex (TSC), a genetic disorder, is rarely associated with HME. Methods We present a case of a newborn with HME with a confirmed mutation in the TSC-1 gene and describe the clinical course, findings on (amplitude integrated) electroencephalography (aEEG), cranial ultrasound (CUS), MRI, and the postmortem evaluation.

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.

Preventing common mental health problems by increasing neighbourhood socioeconomic status: a mental health impact assessment in Rotterdam, the Netherlands.

Neighbourhood socioeconomic status (NSES) has been identified as a determinant of mental health. In this study, we aimed to quantify how many cases of common mental health problems could be prevented by increasing NSES in the most socioeconomically deprived neighbourhoods in Rotterdam, the Netherlands, and how the increases in NSES would affect mental health inequalities. We used publicly available data for conducting a quantitative Health Impact Assessment (HIA) of two counterfactual policy scenarios.