Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

MYH7 p.(Arg1712Gln) is pathogenic founder variant causing hypertrophic cardiomyopathy with overall relatively delayed onset.

Introduction: The MYH7 c.5135G > A p.(Arg1712Gln) variant has been identified in several patients worldwide and is classified as pathogenic in the ClinVar database.

SCN5A-1795insD founder variant: a unique Dutch experience spanning 7 decades.

The SCN5A-1795insD founder variant is a unique SCN5A gene variant found in a large Dutch pedigree that first came to attention in the late 1950s. To date, this is still one of the largest and best described SCN5A founder families worldwide. It was the first time that a single pathogenic variant in SCN5A proved to be sufficient to cause a sodium channel overlap syndrome.

Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens.

Chemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local or global structural distortion. This is of particular importance when the protein in question requires a high degree of structural conservation for inducing a biological outcome such as the elicitation of antibodies to conformationally sensitive epitopes. The HIV-1 envelope glycoprotein (Env) trimer is metastable and shifts between different conformational states, complicating its use as a vaccine antigen.

Comparison of inhibitory effects of irreversible and reversible Btk inhibitors on platelet function.

All irreversible Bruton tyrosine kinase (Btk) inhibitors including ibrutinib and acalabrutinib induce platelet dysfunction and increased bleeding risk. New reversible Btk inhibitors were developed, like MK-1026. The mechanism underlying increased bleeding tendency with Btk inhibitors remains unclear.

Long-term treatment of antipsychotics and combined therapy with other psychotropic medications inducing weight gain in patients with non-affective psychotic disorder: Evidence from GROUP, a longitudinal study.

Introduction: Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics.

Long-term outcome of targeted therapy of underlying conditions in patients with early persistent atrial fibrillation and heart failure: data of the RACE 3 trial.

Aims: The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years.

Prioritizing IVF treatment in the post-COVID 19 era: a predictive modelling study based on UK national data.

Study Question: Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women?

Summary Answer: Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12 months on the probability of conception leading to live birth in women of different age groups with different categories of infertility.

What Is Known Already: Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility.

Development and formative evaluation of patient research partner involvement in a multi-disciplinary European translational research project.

Plain English Summary: Patient and public involvement (PPI) improves the quality of health research and ensures that research is relevant to patients' needs. Though PPI is increasingly evident in clinical and health services research, there are few examples in the research literature of effective PPI in translational and laboratory-based research. In this paper, we describe the development and evaluation of PPI in a multi-centre European project (EuroTEAM - owards arly biomarkers in rthritis anagement) that included both translational and laboratory-based and psychosocial research.

Education and training in adult metabolic medicine: Results of an international survey.

Adult metabolic medicine (AMM) is an expanding medical subspecialty, due to the increasing number of adult patients with inherited metabolic diseases (IMD). However, a formal training and postgraduate education in this field is not available in the majority of countries. Existing adult metabolic specialists (AMS) come from many different backgrounds.

Prevalence of and factors associated with adult-onset asthma in different ethnic groups: The HELIUS study.

Little is known about adult-onset asthma in different ethnic groups. The aim of this study was to examine ethnic differences in the prevalence of adult-onset asthma and factors associated with this phenotype. Cross-sectional data of 23,356 participants of the HELIUS study were used, including Dutch, South-Asian Surinamese, African Surinamese, Moroccan, Turkish and Ghanaian origin participants.

Patient coaching in specialist consultations. Which patients are interested in a coach and what communication barriers do they perceive?

Objective: To characterize patients interested in support by a patient coach to guide them in medical specialist consultations.

Methods: We compared 76 patients interested in a patient coach with 381 patients without such an interest, using a representative panel of patients with a chronic disease in the Netherlands. Independent variables were demographic factors, socio-economic status, perceived efficacy in patient-provider interaction, communication barriers, health literacy, (duration and type of) disease(s) and activation level.

The Analysis of Multivariate Longitudinal Data: An Instructive Application of the Longitudinal Three-Mode Model.

Structural equation modeling is a common technique to assess change in longitudinal designs. However, these models can become of unmanageable size with many measurement occasions. One solution is the imposition of Kronecker product restrictions to model the multivariate longitudinal structure of the data.

Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression.

Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. Aiming to define vitiligo subtypes, we discovered that age-of-onset is bimodal; one-third of cases have early onset (mean 10.3 years) and two-thirds later onset (mean 34.

Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Background: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS.

Methods: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively.

Changing the odds: motives for and barriers to reducing HCV-related sexual risk behaviour among HIV-infected MSM previously infected with HCV.

Background: Among HIV-infected MSM who have been treated for HCV infection, the HCV reinfection rate is high. It is therefore essential to understand their perceptions of HCV risk behaviour and risk-reducing strategies.

Methods: This qualitative study among 20 HCV-infected MSM, the majority treated in the era before direct acting antivirals, provides insight into their ideas, motives, and barriers concerning HCV risk reduction, and aims to strengthen prevention strategies for both primary HCV infection and HCV reinfection.

Experiences with approaches to advance care planning with older people: a qualitative study among Dutch general practitioners.

Objectives: Advance care planning (ACP) with older people needs to be approached differently than ACP with patients with a terminal illness. ACP is still used with only a minority of older patients due to a lack of knowledge regarding appropriate approaches to ACP with older people. General practitioners (GPs) may play a key role in ACP with older people.

Interleukin-17A Inhibition Diminishes Inflammation and New Bone Formation in Experimental Spondyloarthritis.

Objective: It remains unclear if and how inflammation and new bone formation in spondyloarthritis (SpA) are coupled. We undertook this study to assess the hypothesis that interleukin-17A (IL-17A) is a pivotal driver of both processes.

Methods: The effect of tumor necrosis factor (TNF) and IL-17A on osteogenesis was tested in an osteoblastic differentiation assay using SpA fibroblast-like synoviocytes (FLS) differentiated with dexamethasone, β-glycophosphatase, and ascorbic acid.

Low Hartmann's procedure or intersphincteric abdominoperineal resection in the primary treatment of low rectal cancer; a survey among surgeons evaluating current practice.

Background: Low Hartmann's procedure (LHP) and intersphincteric abdominoperineal resection (iAPR) are both surgical options in the treatment of distal rectal cancer when there is no intention to restore bowel continuity. This study aimed to evaluate current practice among members of the Dutch Association of Coloproctology (WCP).

Methods: An online survey among members of the WCP who represent 66 Dutch hospitals was conducted.

Expansion of Interleukin-22- and Granulocyte-Macrophage Colony-Stimulating Factor-Expressing, but Not Interleukin-17A-Expressing, Group 3 Innate Lymphoid Cells in the Inflamed Joints of Patients With Spondyloarthritis.

Objective: Clinical trials of the anti-interleukin-17A (anti-IL-17A) antibody secukinumab have demonstrated a crucial role of the cytokine IL-17A in the pathogenesis of spondyloarthritis (SpA); however, its cellular source in this condition remains a matter of controversy. Group 3 innate lymphoid cells (ILC3s) have been recently identified as potent producers of proinflammatory cytokines, including IL-17A and IL-22, in a number of different tissues. This study was undertaken to characterize the presence and composition of ILCs, and investigate whether these cells are an important source of IL-17A, in the synovial tissue (ST) of patients with SpA.

Development and evaluating multimarker models for guiding treatment decisions.

Background: Despite the growing interest in developing markers for predicting treatment response and optimizing treatment decisions, an appropriate methodology to identify, combine and evaluate such markers has been slow to develop. We propose a step-by-step strategy for analysing data from existing randomised trials with the aim of identifying a multi-marker model for guiding decisions about treatment.

Methods: We start with formulating the treatment selection problem, continue with defining the treatment threshold, prepare a list of candidate markers, develop the model, apply the model to estimate individual treatment effects, and evaluate model performance in the study group of patients who meet the trial eligibility criteria.