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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Björk Werner, Josefin, et al.
(author)
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Factors Influencing Need for Late ASD Closure after Neonatal Repair of Severe Pulmonary Valve Obstruction and Intact Ventricular Septum
- 2018
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In: Cardiology in the Young. - 1467-1107. ; 28:S1, s. 151-151
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Conference paper (peer-reviewed)abstract
- Background: In neonates with critical pulmonary stenosis (CPS) or pulmonary atresia with intact ventricular septum (PAIVS), a nonrestrictive atrial septal defect (ASD) has been speculated to improve the initial clinical course after pulmonary valvotomy (PV) but some concerns exist in terms of its potentially longterm adverse effect on the right ventricle`s (RV) growth and persistent desaturation due to right-to-left (R-L) shunt. Objective: to assess the relationship between the size of ASD and the need for post-valvotomy reinterventions. Method: Patients with PAIVS and CPS treated at our center during 2001- 2015 were reviewed. Exclusion criteria were associated cardiac malformations and hypoplastic RV deemed unsuitable for biventricular circulation. Clinical and echocardiographic data were retrieved from the hospital ́s databases. Results: In total, 48 patients (18 with PAIVS and 30 CPS) were included. The median follow-up was 5 and 8 years, respectively. One patient with PAIVS died on day 3 after surgical valvotomy and Blalock- Taussig shunt (BTs). The majority (89%) of patients with PAIVS had surgical valvotomy whereas transcatheter valvotomy was used in the majority (87%) of patients with CPS. Palliation with BTs or PDA stenting was used in 13 (72%) patients with PAIVS and in 4 (13%) patients with CPS. Reintervention within 1 month after initial repair was needed in 4 (22%) patients with PAIVS and in 4 (13%) patients with CPS. Later reinterventions were performed in in 11(61%) patients with PAIVS and in 10(33%) patients with CPS. Of these, 7 (39%) patients with PAIVS and 5 (17%) with CPS underwent ASD closure due to persistent resting desaturation. The latter did not correlate with ASD size after valvotomy (p>0.1). Initial palliation with BTs was the only variable associated with ASD device closure (p=0.04). No patient required univentricular conversion. Conclusion: Neonatal biventricular repair for severe pulmonary valve obstruction has low mortality but significant need for late reinterventions, mostly consisting of ASD closure due to clinically significant desaturation secondary to R-L shunt. The use of aorto-pulmonary shunt, probably illustrating a more severe form of RV hypoplasia, but not the size of the ASD, predicts the need for later ASD closure due to desaturation.
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| 3. |
- Cirenajwis, Helena, et al.
(author)
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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
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Journal article (peer-reviewed)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
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| 4. |
- Comas-Bru, Laia, et al.
(author)
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Evaluating model outputs using integrated global speleothem records of climate change since the last glacial
- 2019
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:4, s. 1557-1579
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Journal article (peer-reviewed)abstract
- Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data-model comparisons. Here, we illustrate this using 456 globally distributed speleothem delta O-18 records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data-model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on delta O-18 values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices.
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| 5. |
- Gabriels, Charlien, et al.
(author)
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Serial pulmonary vascular resistance assessment in patients late after ventricular septal defect repair.
- 2019
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In: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 282, s. 38-43
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Journal article (peer-reviewed)abstract
- The long-term evolution of pulmonary vascular resistance (PVR) after ventricular septal defect (VSD) repair is unknown. This study serially evaluated resting and exercise PVR after VSD repair in childhood.Patients were enrolled from the outpatient Adult Congenital Heart Disease clinic of the University Hospitals Leuven and compared to age- and gender-matched controls. Participants underwent resting and exercise echocardiography and cardiopulmonary exercise testing at baseline and follow-up. Total PVR was calculated as the ratio of mean pulmonary artery pressure (mPAP) to cardiac output (CO). The slope of the mPAP-CO curve (exercise PVR) was obtained using linear regression analysis.Twenty-seven patients (mean age 31±7years, 70% male) and 18 controls were included. At baseline, patients had larger right ventricular (RV) end-diastolic areas (10±2 vs 9±1cm2/m2, p=0.001) and lower tricuspid annular plane systolic excursion (TAPSE) (17 (17-19) vs 26 (22-28) mm, p<0.001). After 1.1 (1.0-1.5) years follow-up, similar differences in RV areas and TAPSE were found. Patients reached lower peak workload and cardiac index compared to controls at each time point. Peak total PVR was higher (Baseline: 2.7±0.8 vs 2.2±0.3mmHg/L/min, p=0.005; Follow-up: 2.9±0.9 vs 2.1±0.3mmHg/L/min, p<0.001) and the mPAP-CO slope was steeper (Baseline: 2.2±0.8 vs 1.7±0.3mmHg/L/min, p=0.008; Follow-up: 2.5±0.9 vs 1.6±0.3mmHg/L/min, p<0.001) in patients. The mPAP-CO slope in patients correlated inversely with peak oxygen uptake (R=-0.41 and-0.45, p=0.036 and 0.022, baseline and follow-up, respectively).Despite repair, VSD patients seem to show altered pulmonary hemodynamics and RV impairment at rest and exercise, supporting life-long follow-up.
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| 6. |
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| 7. |
- Krog, Jens, et al.
(author)
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Stochastic unfolding of nanoconfined DNA: Experiments, model and Bayesian analysis
- 2018
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 149:21
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Journal article (peer-reviewed)abstract
- Nanochannels provide a means for detailed experiments on the effect of confinement on biomacro-molecules, such as DNA. Here we introduce a model for the complete unfolding of DNA from the circular to linear configuration. Two main ingredients are the entropic unfolding force and the friction coefficient for the unfolding process, and we describe the associated dynamics by a non-linear Langevin equation. By analyzing experimental data where DNA molecules are photo-cut and unfolded inside a nanochannel, our model allows us to extract values for the unfolding force as well as the friction coefficient for the first time. In order to extract numerical values for these physical quantities, we employ a recently introduced Bayesian inference framework. We find that the determined unfolding force is in agreement with estimates from a simple Flory-type argument. The estimated friction coefficient is in agreement with theoretical estimates for motion of a cylinder in a channel. We further validate the estimated friction constant by extracting this parameter from DNA's center-of -mass motion before and after unfolding, yielding decent agreement. We provide publically available software for performing the required image and Bayesian analysis. Published by AIP Publishing.
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| 8. |
- Lacas, Benjamin, et al.
(author)
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Role of radiotherapy fractionation in head and neck cancers (MARCH) : an updated meta-analysis
- 2017
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:9, s. 1221-1237
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Journal article (peer-reviewed)abstract
- Background The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. Methods For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Findings Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8). Interpretation This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. Funding Institut National du Cancer; and Ligue Nationale Contre le Cancer.
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| 9. |
- Massei, Riccardo, et al.
(author)
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A sediment extraction and cleanup method for wide-scope multitarget screening by liquid chromatography–high-resolution mass spectrometry
- 2018
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In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 410:1, s. 177-188
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Journal article (peer-reviewed)abstract
- Previous studies on organic sediment contaminants focused mainly on a limited number of highly hydrophobic micropollutants accessible to gas chromatography using nonpolar, aprotic extraction solvents. The development of liquid chromatography–high-resolution mass spectrometry (LC–HRMS) permits the spectrum of analysis to be expanded to a wider range of more polar and ionic compounds present in sediments and allows target, suspect, and nontarget screening to be conducted with high sensitivity and selectivity. In this study, we propose a comprehensive multitarget extraction and sample preparation method for characterization of sediment pollution covering a broad range of physicochemical properties that is suitable for LC–HRMS screening analysis. We optimized pressurized liquid extraction, cleanup, and sample dilution for a target list of 310 compounds. Finally, the method was tested on sediment samples from a small river and its tributaries. The results show that the combination of 100 °C for ethyl acetate–acetone (50:50, neutral extract) followed by 80 °C for acetone–formic acid (100:1, acidic extract) and methanol–10 mM sodium tetraborate in water (90:10, basic extract) offered the best extraction recoveries for 287 of 310 compounds. At a spiking level of 1 μg mL-1, we obtained satisfactory cleanup recoveries for the neutral extract—(93 ± 23)%—and for the combined acidic/basic extracts—(42 ± 16)%—after solvent exchange. Among the 69 compounds detected in environmental samples, we successfully quantified several pharmaceuticals and polar pesticides.
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| 10. |
- ter Veer, Emil, et al.
(author)
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Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease
- 2018
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 19:3, s. E151-E160
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Research review (peer-reviewed)abstract
- Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.
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