De negatieve teleologie van Hans Jonas : Een ethiek voor de technologische samenleving

Musschenga, A.W. [Promotor]Kirschenmann, P.P. [Copromotor

Chronic Stress Related to Cancer Incidence, including the Role of Metabolic Syndrome Components

Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740–1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738–1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110–36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.</p

Chronic Stress Related to Cancer Incidence, including the Role of Metabolic Syndrome Components

Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740–1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738–1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110–36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.</p

Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study.

To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p &lt; 0.05). There were a number of radiogenomic associations that were also not validated. A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals