Publications by Year: 2026

AIMS: Little is known regarding strategies to improve influenza vaccination uptake among individuals with atrial fibrillation (AF). We assessed the effect of electronically delivered behavioural nudges on influenza vaccination uptake and clinical outcomes according to AF status.

METHODS AND RESULTS: This is a prespecified analysis of the nationwide randomized NUDGE-FLU-CHRONIC trial in which citizens aged 18-64 years with a chronic disease were randomized to usual care or six different electronic nudge letters aiming to increase influenza vaccination uptake during the 2023-2024 influenza season. The primary endpoint was receipt of an influenza vaccine on or before 1 January 2024. We reported absolute differences and relative risks (RRs) of each intervention letter vs. usual care on influenza vaccination uptake and assessed effect modification by AF status using binomial regression. Among 299 881 randomized participants, 19 481 (6.5%) had a history of AF (median age 58.5 years, 27.8% female). During follow-up, 41.5% of participants with a history of AF received influenza vaccination compared with 35.8% of those without (P < 0.001). In the overall population, influenza vaccination uptake was higher among those receiving any electronic nudge letter compared with usual care. AF status modified the absolute effect of any electronic letter on influenza vaccination uptake (P interaction < 0.001): the effect of any electronic letter was higher among those who had a history of AF [45.9 vs. 31.1%; difference: +14.8% points; 99.29% confidence interval (CI) (12.8-16.8), RR: 1.48, 99.29% CI (1.39-1.56)] compared with those without AF [39.1 vs. 27.7%; difference: +11.4% points; 99.29% CI (10.9-12.0), RR: 1.41, 99.29% CI (1.39-1.44)]. Similar results were observed for the individual electronic letter-based nudges.

CONCLUSION: In this prespecified, secondary analysis, electronic nudge letters highlighting the importance of influenza vaccination were especially effective in increasing influenza vaccination uptake among young and middle-aged adults with AF, supporting simple electronic letters as an efficient public health strategy to improve vaccination coverage in high-risk groups.

Familial dysautonomia (FD) is a rare autosomal recessive neurodegenerative disorder caused by a splicing mutation in the ELP1 gene. It predominantly affects the sensory and autonomic nervous systems, with progressive vision loss due to optic neuropathy being a universal and debilitating symptom. Retinal pathology in FD involves progressive thinning of the retinal nerve fiber layer (RNFL), resulting from the degeneration of retinal ganglion cells (RGCs). Notably, FD-associated vision loss has a postnatal onset, offering a critical window for therapeutic intervention before severe visual impairment develops in adolescence. Currently, no approved treatments exist to prevent or reverse vision loss in FD. In this study, we present a novel RNA-based therapeutic approach targeting ELP1 pre-mRNA splicing in the retina. We engineered exon-specific U1 small nuclear RNAs (ExSpeU1s) to enhance inclusion of exon 20 in the mutant ELP1 transcripts in the retina, thereby restoring full-length ELP1 expression. Delivery of ExSpeU1 via adeno-associated virus serotype 2 (AAV2) to the retina improved ELP1 splicing, rescued RGC loss, and visual function in an FD mouse model. These findings highlight ExSpeU1-mediated splicing correction as a promising therapeutic approach for treating optic neuropathy in FD, offering potential to preserve vision and improve quality of life for patients.

BACKGROUND: Although considerable research has investigated diabetes mellitus (DM) as a risk factor for Alzheimer's disease (AD) dementia, the mechanistic understanding of the associations between peripheral and central biological processes in AD and AD within DM remains limited.

METHODS: We performed tandem mass tag-based phosphoproteome profiling on postmortem prefrontal cortex (n = 191), deltoid muscle (n = 191), and antemortem serum (n = 96) from older adults with/without pathologic AD and with/without DM (DM/NDM).

RESULTS: We observed significant brain-muscle and brain-serum correlations in phosphorylated and unphosphorylated peptides. Among individuals with DM, 59 were with AD and 36 were without. Among NDM, 63 were with AD and 33 were without. In a differential expression analysis, muscle phosphorylated seryl-tRNA synthetase 2 (SARS2)-S126 was significantly expressed in pathologic AD, whereas relative abundance of serum alpha-2-HS-glycoprotein (AHSG)-S346 and insulin-like growth factor binding protein 2 (IGFBP2)-S142 showed marginal expression for AD within the DM strata.

CONCLUSIONS: Elucidating central and peripheral proteome crosstalk is valuable for uncovering potential AD biomarkers in accessible (peripheral) biospecimens.

HIGHLIGHTS: We profiled peptides in brain, muscle, and serum biosamples. The study design allowed discovery of diabetes-associated peptides in Alzheimer's disease (AD). Strong brain-muscle, but weaker brain-serum peptide correlations were identified. Muscle seryl-tRNA synthetase 2-S126 was linked to AD pathology. Serum insulin-like growth factor binding protein 2-S142 and alpha-2-HS-glycoprotein-S346 were linked to AD in persons with diabetes.

Most primary retroperitoneal soft tissue tumors are malignant, with liposarcomas and leiomyosarcomas being the most common. However, other sarcomas and benign tumors can also occur in this location. Pathologic evaluation of retroperitoneal sarcomas (RPS) presents unique challenges. Sarcomas are a heterogeneous group with overlapping microscopic features, making accurate classification essential for prognosis and evolving targeted therapies. Core biopsies often capture only a small portion of the tumor, which may result in underestimation of key features such as differentiation, necrosis, and proliferation, leading to undergrading. Surgical management is complicated by the RPS's tendency to involve adjacent organs. Resections are often large and en bloc, and formalin fixation can obscure anatomic landmarks, making it difficult to identify and assess true surgical margins. In addition to the standard data elements required for cancer staging, specific pathologic features of RPS should be reported to aid in prognosis and treatment planning. This position paper/consensus statement was developed by members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) based on evidence and expert opinion. A detailed description of specimen handling, specimen sampling, and the inclusion of the key diagnostic elements required for an accurate pathology report are provided. The aim of this manuscript is to offer a comprehensive critical reappraisal of the role of pathologic evaluation of surgical specimens in RPS surgery, as well as to propose a standard pathology report to harmonize reporting and facilitate future data collection and interpretation for future research development.

INTRODUCTION: Maternal obesity is increasingly linked to adverse health effects across generations, with childhood obesity becoming one of the most critical public health challenges of the twenty-first century. Both a high maternal body mass index (BMI) and excessive gestational weight gain (GWG) are significant and independent predictors of future obesity in both children and adults. This study aims to evaluate the long-term impact of lifestyle interventions during pregnancy on the body composition of mothers and their 15-year-old offspring. Furthermore, we will investigate the influence of these interventions on dysmetabolic traits, and metabolic and inflammatory markers observed in mothers and their offspring 15 years post-pregnancy. The study also aims to examine the relationship between maternal mental health during pregnancy and postpartum, and long-term obesity risk. Finally, we will assess the mental health and health literacy of both mothers and offspring and evaluate its association with obesity risk.

METHODS: This study is a follow-up of a randomized controlled trial. In the original trial, 360 pregnant women with a BMI ≥ 30 kg/m2 from Odense and Aarhus University Hospitals were randomized to receive either lifestyle intervention, including diet counseling and physical activity from 12 weeks gestation until delivery, or standard care. A total of 301 mother-child pairs are eligible for follow-up. The mothers and their offspring will be invited to a 2-h clinical examination, which includes fasting venous blood samples, DXA scans, anthropometric measurements, and questionnaires addressing diet, physical activity, mental health, and health literacy. Examinations will include continuous glucose monitoring and activity tracking for 7-10 days. Our primary endpoint is the effect of lifestyle intervention during pregnancy on offspring body composition measured by DXA scanning.

DISCUSSION: Our data address critical knowledge gaps in understanding childhood obesity. If pregnancy interventions reduce the risk of offspring's obesity, they could serve as a foundation for implementing changes in clinical practice.

TRIAL REGISTRATION: The study was approved by the local ethics committee of the Region of Southern Denmark (S-20220076) and registered on ClinicalTrials.gov (NCT05774652) on March 21, 2023. The findings will be published in international scientific journals and shared with hospitals and policymakers.