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The Clinical Spectrum of Polypoidal Choroidal Vasculopathy in White Patients: A Retrospective Multicenter Cohort Study.
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324461.pdf (Publisher’s version ) (Open Access)PURPOSE: To describe clinical characteristics of polypoidal choroidal vasculopathy (PCV) in a large White cohort. DESIGN: Multicenter retrospective cohort study in 3 tertiary referral centers in the Netherlands. SUBJECTS: White patients with an indocyanine green angiography-confirmed diagnosis of PCV in 1 or both eyes. METHODS: The medical charts and multimodal imaging (MMI) of the included patients were assessed retrospectively by 2 independent assessors. Any discrepancies between graders were resolved by a senior retinal specialist. A predefined set of phenotypic characteristics was graded on MMI, including OCT, color fundus photography, fundus fluorescein angiography, and indocyanine green angiography. MAIN OUTCOME MEASURES: Patients with polypoidal choroidal vasculopathy were distributed among 4 phenotypically different types, based on a previously published description: PCV with drusenoid age-related macular degeneration (AMD): PCV-AMD (type A); PCV without drusen but with a branching neovascular network (BNN): PCV-BNN (type B); isolated polypoidal choroidal vasculopathy (PCV-i) without drusen or a BNN: PCV-i (type C); and PCV with a background of central serous chorioretinopathy (CSC): PCV-CSC (type D). RESULTS: We included 332 eyes of 305 patients with PCV, with 179 of 305 patients being female (58.7%). The average age at diagnosis was 73 years. The included eyes had the following types: PCV-AMD in 188 eyes (58.4%); PCV-BNN in 61 eyes (18.9%); PCV-i in 15 eyes (4.7%); and PCV-CSC in 58 eyes (18.0%). Patients with PCV-AMD were older and more often female than patients with PCV-CSC. The median best-corrected visual acuity of affected eyes was 0.30 logarithm of the minimum angle of resolution (interquartile range, 0.10-0.52), with a large range in each type. A median of 2 polypoidal lesions per eye was found (range, 1-12), with no significant differences between types. The choroidal thickness beneath the fovea and beneath polypoidal lesions was significantly higher in PCV-CSC than in PCV-AMD (both P < 0.001). CONCLUSIONS: Polypoidal choroidal vasculopathy in White patients comprises a spectrum of different phenotypes: it may present with signs of drusenoid AMD, with a background of CSC, or without signs of either diseases. We found a different phenotype distribution when compared with published findings in Asian patients with PCV. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article
Long-term outcomes of pace-and-ablate strategy in patients with atrial fibrillation.
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323946.pdf (Publisher’s version ) (Open Access)BACKGROUND: The pace-and-ablate strategy is second -line therapy to obtain rate control in patients with persistent symptomatic atrial fibrillation (AF) when other treatment options fail. This study aims to evaluate long-term effects on clinical outcomes following pace-and-ablate strategy in AF patients. METHODS: This retrospective study includes patients who underwent successful pacemaker implantation (right ventricular pacing (RVP) or cardiac re-synchronization therapy (CRT)) followed by atrioventricular node ablation (AVNA) between 2010 and 2020. Patients were treated according to the prevailing guidelines. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization (HFH). Secondary endpoints were individual outcomes of all-cause mortality, HFH, and left-ventricular ejection fraction (LVEF) change. RESULTS: Two hundred ninety-eight patients were included, 162 undergoing RVP, and 136 receiving CRT, with a median follow-up of 5.8 years [4.1-8.0]. The primary endpoint occured in 47% of the RVP group and 49% of the CRT group (p = 0.206). All-cause mortality occurred in 36% of the RVP group and in 45% of the CRT group (p = 0.005). HFH occurred in 22% of the RVP group and in 15% of the CRT group (p = 0.328), with 17(10%) upgrades to CRT in the RVP group. Median LVEF in the RVP group remained stable (56% [49-60] to 53% [43-57]; p = 0.081), while it improved in the CRT group (31% [22-38] to 43% [32-51]; p < 0.001). CONCLUSION: Mortality and HFH in patients with AF managed through a pace-and-ablate strategy are high. Reassuringly, LVEF deterioration requiring upgrade to CRT is uncommon in patients undergoing RVP with normal baseline LVEF before AVNA. CRT improves LVEF in patients with reduced LVEF before AVNA
From CoREST to Cancer: Integrative Molecular Studies on Megakaryopoiesis and Retroviral Activity in AML
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325987.pdf (Publisher’s version ) (Open Access)Protein complexes are essential for cellular function, and while their components may be shared across cells, their behaviour varies in cells with different functions. Consequently, drugs targeting these proteins can have cell type–specific effects. This thesis investigates how inhibition of LSD1, part of a protein complex called CoREST, and mutations in its complex partner GFI1B impair the development and function of platelet-producing blood cells. LSD1 inhibition also activates ancient viral elements embedded in the DNA of blood cells, which are normally silent but may modulate responses to therapies for hematologic diseases such as blood cancer. A comprehensive understanding of these elements requires mapping their presence across different types of blood cancers. This thesis provides such a map by analysing ancient virus activity in approximately 800 patients with various blood cancer types, offering insight into how these ancient viral sequences might influence disease mechanisms and treatment outcomes.Radboud University, 02 december 2025Promotores : Reijden, B.A. van der, Martens, J.H.A., Jansen, J.H. Co-promotor : Marneth, A.E.208 p
Exploring Exhaled Breath Analysis in Adults With Chronic Visceral Acid Sphingomyelinase Deficiency to Identify Potential Biomarkers of Pulmonary Involvement
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321768.pdf (Publisher’s version ) (Open Access)13 p
Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023
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Noot bij: Rb. Amsterdam 07 mei 2024, JOR, 2025, 12 (Gedeeltelijke opheffing bankbeslag zodat beslagene advocaat kan betalen)
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325492.pdf (Publisher’s version ) (Open Access)07 mei 202
Venus met een orgeltje. Over de triomf van het gezicht over het gehoor
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Adalimumab serum concentration to choose a subsequent biological DMARD in patients with rheumatoid arthritis (ADDORA-switch): results of a blinded randomised test-treatment trial.
No full textItem does not contain fulltextOBJECTIVES: A substantial proportion of patients with rheumatoid arthritis (RA) discontinue adalimumab due to ineffectiveness. The next treatment step can be another tumour necrosis factor inhibitor (TNFi) or a biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Therapeutic drug monitoring (TDM) of serum drug levels may help guide this choice. This study evaluated whether switching treatments based on adalimumab trough levels is more effective than random switching. METHODS: In this 24-week, multicentre, triple-blinded, randomised controlled trial, patients with RA who stopped adalimumab due to inefficacy (disease activity score based on 28 joint count and C-reactive protein [DAS28-CRP] >2.9) were enrolled. Participants were randomly assigned (1:1) to a TDM-based or random switching (control) strategy. The primary outcome was the difference in mean time-weighted DAS28-CRP between groups at 24 weeks. RESULTS: From July 2020 to November 2023, 83 consecutive patients with RA were included, with 78 initiating a new b/tsDMARD (TDM-based group: n = 38; control: n = 40). The mean time-weighted DAS28-CRP was 3.15 in both groups (TDM: SD, 0.99; control: SD, 1.01; 95% CI of difference: -0.46 to 0.47). There were no significant differences between the groups in flare rates, escape medication use, disease activity, or adverse events. Receiver operating characteristic analyses in the control group found no predictive value of adalimumab levels for response to TNFi or non-TNFi. CONCLUSIONS: Switching treatments based on adalimumab trough levels was not more effective than random switching in patients with RA who failed adalimumab treatment. Therefore, serum drug level measurements to guide therapy choices in this context is not recommended.01 augustus 202
Exploring the influence of urbanization on gut mycobiota through dietary habits in Burkina Faso.
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322306.pdf (Publisher’s version ) (Open Access)BACKGROUND: The phenomenon of urbanization is associated with significant shifts in lifestyle and dietary habits, which can impact the composition of gut microbiota. While variations in gut bacterial communities between rural and urban residents are documented, changes in fungal communities (mycobiota) remain underexplored. This study investigates the impact of urbanization-related dietary shifts on the gut mycobiota in a sub-Saharan African context (Burkina Faso). We analyzed the gut mycobiota composition of individuals from households of rural and semi-urbanized areas, and that of wealthy families living in the capital city (Ouagadougou). We compared the gut mycobiota of three Burkinabè cohorts with that of a cohort of Italian families, as representative of a Western urban lifestyle. Using high-throughput sequencing, we characterized gut mycobiota composition and diversity, assessing changes in accordance with the different dietary patterns and lifestyle. RESULTS: Our findings revealed modifications in gut mycobiota composition along the rural-to-urban gradient. A significant reduction in the alpha-diversity of the gut mycobiota was observed in the cohorts residing in the urban setting compared to those living in rural and semi-urbanized areas. Members of rural households exhibited greater fungal richness and diversity compared to those in urban families, including affluent families in the capital city. Furthermore, we identified 33 fungal amplicon sequence variants (ASVs) significantly associated with the different lifestyle and dietary patterns related to the studied areas. CONCLUSION: The household-level survey of rural and urban settings in Burkina Faso highlighted the impact of urbanization-related dietary shifts on gut mycobiota diversity and composition. The observed loss of fungal diversity and the significant reduction of fungal taxa associated with a rural lifestyle are potential indicators of the shift from a rural to an urban context. In agreement with the hygiene hypothesis, these findings lay the foundation for further studies aiming at investigating the effect that these microbial losses will have on human health, similarly to those already observed for gut bacterial communities
LOFAR-style reconstruction of cosmic-ray air showers with SKA-Low
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321441.pdf (Publisher’s version ) (Closed access)
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321441.pdf (Author’s version preprint ) (Open Access