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Endoscopic papillectomy for laterally spreading lesions of the papilla:a propensity score-matched analysis
No full textBackground:Endoscopic papillectomy is a standard treatment for ampullary lesions, which are typically small and confined to the papillary mound. Laterally spreading lesions (LSLs) of the papilla of Vater are a rare ampullary lesion subtype involving extensive duodenal mucosa. Data on endoscopic papillectomy outcomes for LSLs are limited. This study compared endoscopic papillectomy for ampullary LSLs and non-LSLs in matched cohorts. Methods:The ESAP study (Endoscopic papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for ampullary neoplasm) encompassed 1422 endoscopic papillectomies. Propensity score matching used the nearest-neighbor method for age, sex, co-morbidity, and histologic subtype as cofactors. The main outcomes were complete resection (R0), technical success, complications, and recurrences. Results:Propensity score-based matching identified 232 patients with ampullary lesions (116 non-LSL, 116 LSL) with comparable baseline characteristics. After first intervention, the R0 resection rate, the primary outcome measure, was significantly lower in the LSL group (54.3% [95%CI 45.3%–63.1%]) vs. 69.0% [95%CI 60.4%–76.6%]). Following repeated endoscopic interventions, technical success was similar in both groups (82.8%). After a 22-month median follow-up, the LSL group had significantly more recurrences (41.3% vs. 15.0%) and lower 1- and 3-year disease-free survival rates (61.1% and 44.0% vs. 86.1% and 81.6%, respectively). Complication rates did not differ significantly between the two groups (LSL 32.8% vs. non-LSL 26.7%). Conclusion:LSLs can be safely resected by endoscopic papillectomy, although repeated interventions are necessary to achieve complete resection. The higher risk of recurrence in LSLs necessitates a vigilant surveillance strategy.</p
Young stroke:An update on epidemiology, emerging risk factors, and future research directions
No full textThe incidence of ischemic stroke among young adults (aged 18–49 years) has risen over recent decades, particularly in high-income countries, contrasting with the decline seen in older populations. This trend represents a growing public health concern, as stroke at young age often leads to long-term psychosocial consequences and loss of productive life years. The increasing incidence may partly reflect a higher prevalence of traditional vascular risk factors, as well as the identification of non-traditional risk and trigger factors such as air pollution, sleep apnea, long working hours, vigorous exercise, and illicit drug use. Diagnostic evaluation in this young population is typically more extensive than in older patients, given the broad spectrum of potential underlying causes. A structured, multidisciplinary approach integrating vascular, hematologic, and cardiac assessment is essential for accurate etiological classification. Although functional outcomes are generally favorable, many young stroke survivors experience persistent psychosocial sequelae, including cognitive impairment, depression, anxiety, and fatigue, which significantly affect quality of life. Recurrence risk varies according to stroke etiology, with the lowest rates observed in patients with a cryptogenic stroke. These findings highlight the importance of more tailored secondary prevention strategies, as antiplatelet therapy is not without risks. Further research is needed to identify novel risk and trigger factors, refine prognostic tools, optimize secondary prevention, and develop interventions addressing the psychosocial recovery of young stroke survivors.</p
Assessing Orthogonality in Gene-Environment Interaction Studies Using Polygenic Indices
No full textGene-environment interaction (G×E) studies analyze how environmental conditions cushion or exacerbate differences in genetic endowments. A gene-environment correlation (rGE) between the polygenic index (PGI) and the environmental condition employed in these G×E studies could bias the estimation of the interaction effect. In this brief report, we discuss the limitations of the commonplace correlation-based test used to verify the orthogonality of the PGI and the environment, and propose to complement it with an additional assessment of the genetic correlation between the phenotype corresponding to the PGI of interest and the environmental condition in the G×E analysis sample using bivariate GREML. Our proposed test is straightforward to perform with the data typically available to G×E researchers, and bypasses that the PGI reflects the environmental conditions of the training sample used to calibrate it. Using UK Biobank data, we provide empirical illustrations covering three environmental conditions relevant for educational attainment. We confirm the orthogonality of the Raising of School Leave Age 1972 educational reform and of gender, although gender did not pass the correlation-based test. However, birth district social class and the genetic propensity for educational attainment appear to be intrinsically intertwined
Chimeric Antigen Receptor T-Cell Therapy:More Than an Anti-Cancer Drug
No full textInitially, chimeric antigen receptor (CAR) T-cell therapy was developed to eliminate malignant B cells in haematological B-cell malignancies by targeting CD19 and B-cell maturation antigen. This approach achieved notable success, resulting in (malignant) B-cell depletion and inducing clinical remission in cancer patients. The scope of CAR T-cell therapy has since expanded to various other applications. Recently, CD19-directed CAR T cells have shown promising results in treating B-cell-mediated autoimmune diseases, with patients experiencing long-lasting symptom cessation. Despite these advancements, the unselective targeting of both pathogenic and protective B cells calls for precise immunotherapies capable of selectively removing pathogenic B cells. Therefore, antigen-specific CARs were designed to specifically interact with and deplete subpopulations of target cells expressing the target antigens. Subsequently, modified CARs were introduced by incorporating autoantigens into the sequence, which allowed antigen-specific B cells to bind to CAR T cells. Additionally, antigen-specific CAR T cells have been exploited to treat viral infections. Moreover, CAR technology was expanded to regulatory T cells (Tregs), where CARs can be adopted to induce a tolerogenic environment in target tissues, offering new possibilities in autoimmune diseases, as well as prevention of graft-versus-host disease in haematopoietic stem cell transplantation and transplant rejection in the setting of solid organ transplantation. Although CAR T cells and CAR Tregs are promising and broadly explored, safety issues must be addressed and possible solutions thoroughly investigated. This review outlines the broad potential of CAR-based therapies in autoimmunity, virology and transplantation while addressing the need for solutions to current safety issues.</p
Atherosclerosis after pre-eclampsia:systematic review and meta-analysis
No full textObjective: Pre-eclampsia complicates up to 8% of pregnancies and is associated with increased risk of ischemic cardiac and cerebral disease, which may be prevented through management of cardiovascular risk when early disease stages are detected. This meta-analysis aimed to determine the prevalence of clinical and subclinical atherosclerosis in women after pre-eclamptic vs non-pre-eclamptic pregnancy with advancing maternal age.Methods: A systematic search of the literature was conducted in PubMed, Embase and Web of Science for studies reporting on the prevalence of atherosclerosis in women with a previous pre-eclamptic pregnancy and those with a previous uncomplicated pregnancy. Any systemic atherosclerosis documented using ultrasound or computed tomography was included. Random-effects meta-analysis was used to compute the odds ratio (OR) with 95% CI for the association between pre-eclampsia and the presence of atherosclerosis. Subgroup analysis was conducted according to average maternal age at evaluation. Results: A total of 11 articles were included (13 217 participants). The average maternal age at evaluation ranged from 32 to 60 years. Within this age range, the pooled OR for the presence of atherosclerotic plaque after pre-eclampsia was 1.57 (95% CI, 1.39–1.78). The pooled OR of developing atherosclerotic plaque after a pre-eclamptic vs non-pre-eclamptic pregnancy increased gradually with advancing maternal age. The OR was not significant in the 30–39-year-old group (0.64 (95% CI, 0.10–4.15)), but the odds of finding an atherosclerotic plaque were significantly increased after pre-eclamptic pregnancy in the 40–49-year-old group (OR, 1.59 (95% CI, 1.34–1.89)) and 50–60-year-old group (OR, 2.00 (95% CI, 1.30–3.08)). At any given age, the percentage plaque prevalence in formerly pre-eclamptic women was roughly equal to that seen 10 years later in women with a previous non-pre-eclamptic pregnancy.Conclusions: Women with a previous pre-eclamptic pregnancy exhibit atherosclerosis more frequently and approximately 10 years earlier compared with women with a previous non-pre-eclamptic pregnancy. Targeted primary prevention is required to reduce morbidity and mortality from premature cardiovascular disease in women after pre-eclampsia.</p
Assessing the co-occurrence of psychopathology and resilience:Evidence for the dual-factor model of mental health using a data-driven approach from a multi-ethnic youth epidemiology study in south-east Asia
No full textBackground: While studies have consistently shown that resilience is a protective factor for youth psychopathology, less is known about the co-occurrence between resilience and youth psychopathology symptoms particularly in the south-east Asian context, based on the dual-factor model (DFM) of mental health. Methods: Data was taken from the nationally-representative Youth Epidemiology and Resilience (YEAR) study conducted in Singapore. The analysis, which included 3336 Singapore youth aged 10 to 18, used a person-centered approach (i.e. Latent Profile Analysis) to identify subgroups of youths based on co-occurring resilience and psychopathology (across both internalising and externalising symptoms) as measured by the Youth Self-Report. Examined correlates include sociodemographic variables, perceived stress and academic expectations and stress. Findings: Six profiles were found – “Flourishing” (21.3 %), “Moderately Resilient & Moderately Symptomatic” (33.3 %), “Moderately Resilient & Moderately Symptomatic (Externalising)” (11.5 %), “Struggling (Internalising only)” (17.1 %), “Struggling (Co-morbid)” (5.9 %) and “Vulnerable” (10.9 %). The profiles differed in terms of various socio-demographic factors, perceived stress and academic expectations and stress. Interpretation: Findings demonstrate empirical support for the DFM in the south-east Asian context. By using a data-driven approach, this study found unique profiles that are not typically found in other DFM studies. Of significance, the “vulnerable” profile, who have low psychopathology but also low resilience, had significantly higher perceived stress compared to the “Moderately Resilient & Moderately Symptomatic” profile after adjusting for socio-demographic covariates, highlighting the important role of resilience. Clinical implications include the urgent need to include positive mental health indicators in a holistic assessment of youths' overall psychological functioning.<p/
Dynamic networks of prolonged grief symptoms in daily life
No full textBackground: According to network theories, mental disorders, including prolonged grief disorder (PGD), comprise networks of dynamically connected symptoms. Examining how prolonged grief symptoms are connected over time could reveal the patterns driving their persistence. This study provides the first empirical investigation of prolonged grief symptom networks using self-reported data on prolonged grief assessed multiple times daily. Methods: Adults whose partner, family member, or friend died on average 30 months ago (N = 229, 80 % women, Mage = 51) rated prolonged grief symptom intensity using 11 items (e.g., “In the past three hours, I found myself yearning for him/her”) five times per day for two weeks. We used a two-step multilevel vector autoregressive model to produce between-person, contemporaneous, and temporal networks. Results: In the between-person network, yearning and sadness were the most strongly and positively connected symptoms. In the contemporaneous network, yearning, preoccupation, and sadness formed a cluster of positively connected symptoms. Simultaneously, difficulty reintegrating after the loss, emotional numbness, meaninglessness, and loneliness due to the loss formed another positively connected symptom cluster. In the temporal network, emotional numbness had the greatest positive influence on other prolonged grief symptoms at the subsequent timepoint. Conclusion: We propose that targeting emotional suppression, promoting flexible emotion regulation, and supporting integrated continuing bonds (approach-behaviors) and targeting avoidance of the reality of the loss (avoidance-behaviors) may help people to adapt to loss.</p
Progression of stenosis severity and aortopathy in adult patients with congenital aortic stenosis
No full textBackground:Congenital aortic stenosis (AS) is a heterogeneous disease. However, repeated data describing disease progression is limited, especially in adults. Therefore, the objective of this study is to investigate progression of peak velocity and aortic dimensions in adult congenital AS patients, identifying markers for fast progression.Methods:Adult patients (aged 18–55 years) with a native aortic valve and at least mild AS at baseline registered in the Dutch CONCOR registry between 2001 and 2019 from all six tertiary expert centers for congenital heart disease were included. Patients with severe aortic regurgitation at baseline or no available echocardiograms during follow-up were excluded. Data on ascending aortic dimensions and peak velocity changes over time were analyzed using mixed models until death, aortic valve replacement or March 1, 2023.Results:402 patients (63 % male) were included with a median age of 26 [IQR 19–41] years and peak velocity of 3.1 [IQR 2.7–3.6] m/s. Median follow-up time was 6.8 [IQR 3.8–11.6] years. Peak velocity significantly progressed over time with 0.06 ± 0.10 m/s/year (p < 0.001), independent of baseline velocity. Older age and concentric left ventricular (LV) remodeling were associated with faster progression. Mean progression of ascending aortic dimension was 0.4 ± 0.5 mm/year (p < 0.001), with faster progression in younger patients (p = 0.002). No correlation between aortic growth rate and stenosis severity progression was seen (r = 0.001, p = 0.98).Conclusion:Overall disease progression was slow in adult congenital AS patients, and independent of baseline peak velocity. Progression of stenosis should be monitored more carefully in older patients and patients with signs of concentric LV remodeling
The E-AHPBA-ESSO-Innsbruck consensus recommendations on peri- and postoperative management following liver resection
No full textBACKGROUND: Liver surgery carries a high risk of complications due to the complex interplay of patient-related factors, disease characteristics, and liver function. Expertise is essential for healthcare professionals managing hepatobiliary patients. This European consensus provides evidence-based guidance on selected aspects of peri- and postoperative care. METHODS: A modified Delphi process was used to achieve consensus, with a 70% agreement threshold. The expert panel comprised hepatobiliary surgeons, anaesthetists, hepatologists, a specialist nurse, and a physiotherapist. A systematic literature search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases. Six topics were addressed: thromboprophylaxis; perioperative antibiotics; prehabilitation/nutrition/mobilization; bile leak including bilioenteric anastomosis leaks; post-hepatectomy haemorrhage; and post-hepatectomy liver failure (PHLF). Evidence appraisal and statement development followed Scottish Intercollegiate Guidelines Network methodology. A patient representative reviewed the guideline. RESULTS: Searching the literature yielded 204 included publications from an initial 6514. Thirty-two statements were formulated with a median evidence level of 2. Evidence strength varied by topic with noticeably lower evidence levels in complex surgery settings and less prevalent conditions. In some topics, study heterogeneity and specific inclusion criteria resulted in conditional recommendations, despite high-level evidence. Notably, the weakest evidence was found for perioperative thromboprophylaxis and PHLF management. Strong recommendations were formulated for prehabilitation, early postoperative mobilization, and avoidance of routine drain use. Several evidence gaps warranting multicentre studies were identified. CONCLUSION: Optimizing peri- and postoperative care after liver resection remains challenging. Standardizing key practices and addressing evidence gaps through collaborative research are vital to improve outcomes.</p
Unraveling the intersection of aging and Parkinson’s disease:a collaborative roadmap for advancing research models
No full textAging is the most significant risk factor for Parkinson’s disease (PD), yet its role remains underexplored. The International Network for Parkinson’s Disease Modelling and Aging (PD-AGE), funded by the Michael J. Fox Foundation, was established to address these challenges. Through collaborative efforts, the PD-AGE mouse-model working group developed a roadmap to prioritize mouse models, reach consensus on experimental approaches, and standardize protocols to investigate the intersection of aging and PD.</p