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Understanding consumption of animal- and plant-based protein sources in the Netherlands:A stakeholder-driven causal loop diagram
No full textCurrent consumption of animal-based protein sources is environmentally unsustainable and poses risks to human health, animal welfare, and food security. Policymakers in many countries seek to reduce the consumption of animal-based protein sources. However, this transition is affected by many factors, and it remains unclear how they interact and what their potential is for stimulating systemic change. This study synthesized stakeholders’ perspectives on factors driving the consumption of animal- and plant-based protein sources into a Causal Loop Diagram (CLD), visualiing factors and their cause-and-effect relationships. Three Group Model Building sessions with 28 stakeholders (consumers, researchers, industry representatives, policymakers, interest group members) from the Netherlands informed the CLD. The Action Scales Model was used to categorize factors into system levels (events, structures, goals, and beliefs), providing insights into their potential for systemic change. The resulting CLD reveals the complexity of protein consumption across five interconnected subsystems: 1) Individual Aspects, 2) Social Interactions & Culture, 3) Physical Food Environment, 4) Food Industry & Natural Food Environment, and 5) Politics & Regulation. The high interconnectivity indicates isolated interventions are unlikely to be sufficient for systemic change, as feedback mechanisms may counteract or neutralize their effects. Addressing multiple elements across the system is thus essential to accelerate the protein transition. This study provides a foundation for understanding the system dynamics shaping consumption of animal- and plant-based protein sources. However, further research is needed to incorporate quantitative weighting, determine the relative importance of mechanisms and identify leverage points for systemic change to guide policy development.</p
Left ventricular assist device utilization across the different regions of the Netherlands
No full textINTRODUCTION: The accessibility of left ventricular assist device (LVAD) therapy is a crucial factor in the survival and quality of life of patients suffering from advanced heart failure. However, there is a lack of clarity regarding the utilization of this therapy across regions in the Netherlands as well as whether any disparities exist based on socioeconomic status (SES). This study aimed to determine the utilization of LVAD therapy at a regional level using administrative data and to identify potential disparities based on SES by comparing postal code data to demographic governmental data.METHODS: All patients aged 16 or older who underwent a primary LVAD implantation between 2015 and 2024 were included. The data was visualized with a heatmap using Python.RESULTS: A total of 710 patients received an LVAD during the study period. LVAD utilization was lower in the southernmost regions compared to the northernmost regions and varied in the central regions. An ANOVA test between SES groups did not show significant differences in LVAD utilization (p = 0.20).CONCLUSION: The findings of this study indicate that there are notable variations in the utilization of LVAD therapy across different geographical regions in the Netherlands. Nevertheless, no differences in LVAD use were found between areas with different SES categories. Future research should focus on identifying the underlying factors associated with referral for advanced heart failure therapies to ensure equitable access to LVAD therapy.</p
Multi-omics profiling of chronic immune-mediated skin diseases:SKINERGY protocol and strategic evaluation
No full textBackground: The Dutch flagship project Next Generation ImmunoDermatology (NGID) aims to profile five chronic immune-mediated inflammatory skin diseases: atopic dermatitis (AD), plaque psoriasis (PSO), hidradenitis suppurativa (HS), chronic spontaneous urticaria (CSU) and cutaneous lupus erythematosus (CLE) in comparison with cutaneous T-cell lymphoma subtype mycosis fungoides (MF) and healthy volunteers. Within NGID, a clinical study entitled: ‘SKIN disease profiling by an Exploratory, pRospective, biomarker study in dermatoloGY practice (SKINERGY)’ will be conducted as a multicentre, parallel-cohort, open-label, observational, longitudinal basket study. Objectives: Objectives include evaluation of disease-related characteristics in comparison to those of healthy volunteers and evaluation of biomarkers for disease stratification and (targeted) treatment response in patients in a real-world clinical setting. Additionally, differences and similarities in disease characteristics between diseases, changes over time, and profiles of responders versus non-responders will be evaluated. Methods: Patients with AD (N = 120), PSO (N = 160), HS (N = 80), CSU (N = 120) and CLE (N = 120) will be enrolled in groups of N ≤ 40 patients per treatment. Matched healthy volunteers (N = 120) and the MF cohort (N = 120) will serve as control groups. Assessments include blood sampling, skin punch biopsies, tape stripping, skin swabs, (multimodal) imaging, tele-health and patient- and physician-reported outcomes. This manuscript describes the study protocol prior to data collection and its strategic evaluation of multi-omics profiling. Patient advocacy groups co-defined the research agenda and contributed to study design and informed consent document development, ensuring alignment with patients' needs and real-world relevance. Results: SKINERGY will generate a machine learning-ready dataset with information about changes in various biomarkers over time, including histology, metabolomics, spatial proteomics, transcriptomics, lipidomics, microbiomics, imaging biomarkers, tele-health, patient-reported outcome measures (PROMs) and clinical parameters. Conclusion:Identified biomarker profiles within SKINERGY may guide targeted treatment selection, enhance targeted therapeutic response in clinical practice and improve understanding of disease pathology in chronic immune-mediated skin diseases.</p
Macronutrient quality and colorectal cancer outcomes:evidence from the PLCO screening trial
No full textBackground: No previous study has assessed the relationship between macronutrient quality and colorectal cancer (CRC) incidence and mortality. Thus, to further explore the associations between macronutrient quality and CRC risk, we conducted a large prospective cohort study involving 101,709 people in the United States from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: Our study population was derived from 154,887 adults aged 55 to 74 years who were recruited from 10 screening centers in the United States. The macronutrient quality index (MQI) was calculated based on dietary history questionnaire (DHQ). Cox regression analysis was utilized to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between MQI and CRC incidence and mortality. We used subgroup analyses to identify potential effect modifiers. Sensitivity analysis was performed to ensure the study findings were robust. Results: During the study period, 1,100 colorectal cancer (CRC) diagnoses and 314 CRC-related deaths were recorded. Higher adherence to the MQI was significantly associated with reduced CRC risk, demonstrating a 22% lower incidence (HR Q4 vs. Q1: 0.78; 95% CI: 0.65–0.93; p = 0.006 for trend) and 38% lower mortality (HR Q4 vs. Q1: 0.62; 95% CI: 0.44–0.86; p = 0.001 for trend) in the highest vs. lowest quartiles. These associations were robust across sensitivity analyses. Subsite-specific analyses revealed pronounced protective effects for distal colon cancer incidence (36% reduction; HR: 0.64; 95% CI: 0.43–0.96; p = 0.010 for trend) and mortality (56% reduction; HR: 0.44; 95% CI: 0.19–1.01; p = 0.037 for trend), with significant mortality reductions also observed for proximal colon cancer (34%; HR: 0.66; 95% CI: 0.44–1.00; p = 0.031 for trend).Conclusion: Our findings suggest focusing on higher quality of macronutrient consumption may be an effective approach to reduce the risk of CRC in the US population.</p
Polycystic ovary syndrome and anti-Müllerian hormone:Integrating genetics in etiology and diagnosis
Get PDFCatching a moving target:Phenotypic plasticity in the initiation and progression of intestinal cancer
Get PDFThis thesis investigates phenotypic plasticity in intestinal cancer, with a focus on how epithelial cells modify their characteristics in response to environmental signals, particularly during cancer initiation and metastasis. We explore the impact of inflammation—a significant risk factor for colorectal cancer—on cellular plasticity of differentiated Paneth cells, which can transition into tumor-initiating cells under inflammatory conditions. Our research indicates that secretory goblet cells also play a role in tumorigenesis, with aberrant profiles associated with ulcerative colitis and serrated polyps.In the second part, we examine the metastatic progression of colorectal cancer, identifying particular cell populations, such as 'Epcam-low' cells, which demonstrate increased plasticity, mobility, and invasiveness. These cells undergo the epithelial-mesenchymal transition, contributing to the disease's aggressive nature. By integrating transcriptomic analyses from clinical specimens with experimental models, this thesis sheds light on the complex mechanisms driving plasticity in cancer and underscores the potential for developing new therapeutic strategies that target phenotypic plasticity in colorectal cancer.<br/
Locoregional treatments for biliary cancer:Intra-arterial chemotherapy and primary percutaneous stenting
Get PDFBiliary cancer is a rare disease with a poor prognosis. Patients are mostly ineligible for surgical resection due to distant metastases, locally advanced disease, or poor performance status. These patients often develop jaundice, because the tumor blocks the bile ducts. To resolve this, one or more biliary stents need to be placed. Endoscopic drainage is standard care internationally. The stent placement is performed via the bowel. Unfortunately, patients often develop pancreatitis and recurrent cholangitis after this procedure, due to bacterial colonization of the bile ducts. Consequently, most patients require multiple reinterventions. The 90-day mortality rate after palliative drainage is 35%, and only 20% become eligible for any palliative systemic treatment. Only after adequate biliary drainage without cholangitis patients with biliary cancer typically qualify for palliative chemotherapy, targeted treatments, and immunotherapy. In a phase II trial, the TESLA trial, we performed primary percutaneous stenting where biliary stents are placed directly into the bile ducts without crossing the ampulla and without leaving an external biliary drain. In 67 patients, no cholangitis or pancreatitis was observed. Primary percutaneous stenting for palliative patients had a low incidence of drainage-related complications and reinterventions. No drainage-related 90-day mortality was observed. Most patients (61.2%) started with palliative systemic treatment.In another phase II trial, the PUMP II trial, we performed hepatic arterial infusion pump (HAIP) chemotherapy. This is a treatment with chemotherapy (floxuridine) delivered directly into the liver. A subcutaneous pump is surgically implanted. This pump is connected to the artery leading to the liver, allowing almost no chemotherapy to enter the rest of the body, resulting in minimal side effects for the patients. This treatment originally comes from the Memorial Sloan Kettering Cancer Center in New York. However, systemic chemotherapy (gemcitabine and cisplatin) is the standard care internationally, with a median overall survival of 12 months. During our study, HAIP chemotherapy was given in addition to the standard treatment. In 50 patients, the median overall survival was 23 months, and 1 in 3 patients is still alive after 3 years, compared to only 3% with the standard care.<br/
