Leiden University Scholary Publications
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The time-course of phonological encoding: insights from time-resolved MVPA
Get PDFTheoretical and Experimental Linguistic
Reintroduction of palliative intent FOLFIRINOX chemotherapy in a real world pancreatic cancer cohort
Get PDFBackgroundFOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) can improve the prognosis of advanced pancreatic ductal adenocarcinoma (PDAC). Upon progression after a therapy-free interval it is not uncommon to reintroduce FOLFIRINOX, depending on the response and progression free interval after first-line FOLFIRINOX. The aim of this study is to provide an overview of the use and effectiveness of FOLFIRINOX reintroduction in daily practice.Patients and methodsPatients with locally advanced and metastatic PDAC, diagnosed between 2015 and 2018, who started systemic treatment with palliative intent were selected from the Netherlands Cancer Registry (NCR). Overall and progression free survival (OS, PFS) were evaluated using Kaplan-Meier curves with log-rank tests.ResultsIn this cohort of 2092 patients, most were treated with first-line FOLFIRINOX (1381; 66 %). The median OS was 9.0 months. A total of 388 patients (28 %) received subsequent systemic therapy after first-line FOLFIRNOX; 119 (30.7 %) patients were re-treated with FOLFIRINOX after a minimum of 3 months treatment interruption while 269 patients received other therapies, mostly gemcitabine/nab-paclitaxel or gemcitabine monotherapy. The median therapy-free interval between first-line FOLFIRINOX and FOLFIRINOX reintroduction was 7.0 months (p25-p75: 4,6–10,6). Patients underwent a median of 5 cycles (range: 1–32) during initial treatment and 5 cycles (range: 1–28) during FOLFIRINOX reintroduction. Median OS after FOLFIRINOX reintroduction was 23.4 months, and median progression-free survival was 6.8 months.ConclusionReintroduction of FOLFIRINOX after at least 3 months therapy-free interval is used in daily practice and seems a reasonable treatment option based on a favorable OS and PFS in a small subset of patients.Cellular mechanisms in basic and clinical gastroenterology and hepatolog
Semi-quantitatively scored apical extent of disease predicts change in total lung capacity in patients with systemic sclerosis and early interstitial lung disease
Get PDFBackgroundPulmonary function tests (PFTs) and extent of ILD on HRCT predict mortality in systemic sclerosis associated interstitial lung disease (SSc-ILD). It is not known whether location and type in addition to extent of affected lung parenchyma are associated with PFTs changes.MethodsSSc patients from a targeted healthcare program were included when PFTs and visually scored concomitant chest HRCT and PFTs at one year follow-up were available. Lung parenchyma of SSc patients was semi-quantitatively scored by visual assessment (reticulation, ground glass opacities, emphysema and disease extent) at five levels from apex to base. Regression analysis after linearity check and excluding multicollinearity was used to predict changes in PFT parameters (TLC, total lung capacity; FVC, forced vital capacity; DLCO, diffusion capacity for carbon monoxide).ResultsA total of 185 patients were included (85% female, mean age at first symptoms 40 years). All HRCT variables correlated with PFT parameters cross-sectionally. Disease extent and reticulation at the apices (level 1), reticulation at level 2, disease extent and reticulation at level 3 all correlated significantly with TLC (r 0.151–0.17, p 2 0.024, p 0.021) and when excluding patients with emphysema or pulmonary hypertension, reticulation at level 3 predicted change in TLC (adjusted R2 0.026, p 0.020).ConclusionsIn patients with systemic sclerosis and lung involvement, disease extent and reticulation at the mid-upper zones predicted change in TLC which may be of clinical importance.Pathophysiology and treatment of rheumatic disease
Activation of classifiers in word production: insights from lexico-syntactic probability distributions
Get PDFTheoretical and Experimental Linguistic
Proactive mapping and preventive ablation reduce defibrillator implantation rates in tetralogy of Fallot
Get PDFBACKGROUND In patients with repaired tetralogy of Fallot (rTOF) and spontaneous ventricular tachycardia (VT), transection of slow-conducting anatomical isthmus (SCAI) by ablation results in excellent long-term VT-free survival. In patients without prior VT, proactive electroanatomical mapping and preventive SCAI ablation may impact patient selection for primary prevention implantable cardioverter-defibrillator (ICD) implantation. OBJECTIVES The purpose of this study was to evaluate long-term outcomes after proactive electroanatomical mapping and ablation of SCAI and its impact on patient selection for primary prevention ICD implantation, compared with current risk stratification methods in rTOF patients without prior VT. METHODS Consecutive rTOF patients without prior VT who underwent electroanatomical mapping for VT substrate identification were included (2005-2020). After successful SCAI ablation, ICD implantation was offered but was subject to shared decision making. The potential eligibility for ICD implantation was retrospectively determined using the following: 1) a clinical risk score; 2) guideline-recommended risk factors (American Heart Association [AHA] 2018 guidelines without late gadolinium enhancement [LGE] on cardiac magnetic resonance [CMR] information, AHA 2018 guidelines with LGE-CMR information, European Society of Cardiology [ESC] 2022 guidelines); and 3) electroanatomical mapping and SCAI ablation results. In the latter, patients with a nontransected SCAI, VT substrates remote from anatomical isthmuses, or severe right-/left ventricular dysfunction qualified for ICDs. RESULTS A total of 97 patients were included (age 35 f 16 years, 57 men); 33 patients (34%) had SCAI and 19 (20%) had inducible monomorphic VT (17 of 19 SCAI-dependent VT). Successful SCAI transection was achieved in 87% (26 of 30 patients) in whom attempted, without complications. In total, 13 patients received an ICD implantation. During a median follow-up of 58 months (Q1-Q3: 30-99 months), 4 patients (4%) had VT, all after ablation failure. According to clinical risk score, AHA 2018 guidelines without LGE-CMR information, AHA 2018 guidelines with LGE-CMR information, and ESC 2022 guidelines, 49 (51%), 24 (25%), 31 (32%), and 48 patients (49%) would have qualified for ICDs, respectively. After proactive mapping and preventive ablation, 11 patients (11%) remained ICD candidates, including all 4 with a VT event during the follow-up (annual VT risk 7%/y). CONCLUSIONS Long-term outcome of rTOF patients without SCAI is excellent. Proactive electroanatomical mapping and preventive SCAI ablation may significantly reduce primary prevention ICD implantation rates compared with current risk prediction methods. (JACC. 2025;85:1695-1705) (c) 2025 by the American College of Cardiology Foundation.Thoracic Surger
Rotterdam Oncology Documentation (RONCDOC): a high-quality data warehouse and tissue collection for head and neck cancer
Get PDFBackgroundEvery year, almost 900.000 people are diagnosed with head and neck cancer (HNC) worldwide. HNC contains many different subsites and a large variability in tumor biology. This often results in small and/or heterogeneous study populations. Developing overarching databases is an efficient solution to collect and analyze data of these smaller subsets of patients and to facilitate data sharing among research groups. The few existing large databases often include only basic characteristics. In addition, hospital-based cohorts that include more variables are often not collected consecutively, resulting in selection bias. Therefore, we established a hospital-based cancer registry system “Rotterdam Oncology Documentation” (RONCDOC), a complete and consecutive data warehouse and tissue collection for HNC, directly registered at the source. The primary aim of this paper is to report on our data collection protocol in order to make the RONCDOC data accessible and reusable for other researchers, and to offer a blue print to other consortia planning to establish their own data warehouse.MethodsData collected in the Netherlands Cancer Registry (NCR) of patients with HNC were obtained from the Netherlands comprehensive cancer organization (IKNL) and merged with corresponding data from the electronic patient file (EPF). The data were manually verified using the EPF, and enriched with additional variables from the EPF according to an extensive data entry protocol. Furthermore, a comprehensive validation protocol was developed to guarantee the quality of the data. Tissue microarrays (TMAs) were constructed from resection specimens of patients with primary oral squamous cell carcinoma.ConclusionWith RONCDOC, we have established a consecutive and high-quality data warehouse for HNC. This paper outlines the essential steps for establishing such a data warehouse, offering a blueprint for other consortia.Trial registrationThis study was approved by the ethics committee of the Erasmus Medical Center (MEC-2016–751).Otorhinolaryngolog
Onderzoek registerfunctionaliteit voor actieve en passieve openbaarmaking
Get PDFDit onderzoek betreft een internationale vergelijking van digitale registerfunctionaliteiten voor de openbaarmaking van overheidsinformatie.Het woord ‘informatieregister’ roept associaties op met één uitputtend online overzicht van alle (beschikbare) overheidsdocumenten. Voor het onderzoek is met een bredere blik gekeken. Registerfunctionaliteiten omvatten in dit onderzoek alle mogelijke voorzieningen voor het indexeren en ontsluiten van (in dit geval) overheidsinformatie en vormen een brug tussen de interne informatiehuishouding en de actieve en/of passieve openbaarmaking van overheidsinformatie.The Legitimacy and Effectiveness of Law & Governance in a World of Multilevel Jurisdiction
Networks in aquatic communities collapse upon neonicotinoid‐induced stress
Get PDFFreshwater ecosystems worldwide are under pressure from neonicotinoid insecticides. While it is recognised that communities of species are responsible for ecosystem functioning, it remains unknown if neonicotinoid-induced community transformations negatively affect ecosystem functioning. Therefore, we employed an experimental approach with 36 naturally established freshwater ecosystems exposed to increasing field-realistic concentrations of the neonicotinoid thiacloprid. Upon exposure, we found severe degradation of ecosystem functioning in the form of loss of organic matter consumption and dramatic shifts in primary productivity. This functional decline coincides with strongly eroded species co-occurrence networks to the point that these are indistinguishable from randomised assemblages of species. Together, these findings show how current environmental concentrations of a neonicotinoid can strongly disrupt freshwater ecosystem functioning via degradation of the invertebrate food web. Since this dramatic ecosystem degradation occurs below nearly all identified ecotoxicological risks, we call here for the reconsideration of the use of these insecticides.Environmental Biolog
