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1.
  • Abel, I, et al. (author)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Journal article (peer-reviewed)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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2.
  • Romanelli, F, et al. (author)
  • Overview of the JET results
  • 2011
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Journal article (peer-reviewed)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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3.
  • Lloyd, B., et al. (author)
  • Overview of physics results from MAST
  • 2011
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9, s. 094013 (paper no.)-
  • Journal article (peer-reviewed)abstract
    • Major developments on the Mega Amp Spherical Tokamak (MAST) have enabled important advances in support of ITER and the physics basis of a spherical tokamak (ST) based component test facility (CTF), as well as providing new insight into underlying tokamak physics. For example, L-H transition studies benefit from high spatial and temporal resolution measurements of pedestal profile evolution (temperature, density and radial electric field) and in support of pedestal stability studies the edge current density profile has been inferred from motional Stark effect measurements. The influence of the q-profile and E x B flow shear on transport has been studied in MAST and equilibrium flow shear has been included in gyro-kinetic codes, improving comparisons with the experimental data. H-modes exhibit a weaker q and stronger collisionality dependence of heat diffusivity than implied by IPB98(gamma, 2) scaling, which may have important implications for the design of an ST-based CTF. ELM mitigation, an important issue for ITER, has been demonstrated by applying resonant magnetic perturbations (RMPs) using both internal and external coils, but full stabilization of type-I ELMs has not been observed. Modelling shows the importance of including the plasma response to the RMP fields. MAST plasmas with q > 1 and weak central magnetic shear regularly exhibit a long-lived saturated ideal internal mode. Measured plasma braking in the presence of this mode compares well with neo-classical toroidal viscosity theory. In support of basic physics understanding, high resolution Thomson scattering measurements are providing new insight into sawtooth crash dynamics and neo-classical tearing mode critical island widths. Retarding field analyser measurements show elevated ion temperatures in the scrape-off layer of L-mode plasmas and, in the presence of type-I ELMs, ions with energy greater than 500 eV are detected 20 cm outside the separatrix. Disruption mitigation by massive gas injection has reduced divertor heat loads by up to 70%.
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4.
  • Lönnroth, J. -S, et al. (author)
  • Integrated ELM modelling
  • 2006
  • In: Contributions to Plasma Physics. - : Wiley. - 0863-1042 .- 1521-3986. ; 46:7-9, s. 726-738
  • Journal article (peer-reviewed)abstract
    • This paper presents a short overview of current trends and progress in integrated ELM modelling. First, the concept of integrated ELM modelling is introduced, various interpretations of it are given and the need for it is discussed. Then follows an overview of different techniques and methods used in integrated ELM modelling presented roughly according to physics approached in use and in order of increasing complexity. The paper concludes with a short discussion of open issues and future modelling requirements within the field of integrated ELM modelling.
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5.
  • Imbeaux, F., et al. (author)
  • A generic data structure for integrated modelling of tokamak physics and subsystems
  • 2010
  • In: Computer Physics Communications. - : Elsevier BV. - 0010-4655. ; 181:6, s. 987-998
  • Journal article (peer-reviewed)abstract
    • The European Integrated Tokamak Modelling Task Force (ITM-TF) is developing a new type of fully modular and flexible integrated tokamak simulator, which will allow a large variety of simulation types This ambitious goal requires new concepts of data structure and workflow organisation, which are described for the first time in this paper The backbone of the system is a physics- and workflow-oriented data structure which allows for the deployment of a fully modular and flexible workflow organisation. The data structure is designed to be generic for any tokamak device and can be used to address physics simulation results, experimental data (including description of subsystem hardware) and engineering issues (C) 2010 Elsevier B.V All rights reserved
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6.
  • Imbeaux, F., et al. (author)
  • Data structure for the European Integrated Tokamak Modelling Task Force
  • 2008
  • In: 35th European Physical Society Conference on Plasma Physics, EPS 2008 Combined with the 10th International Workshop on Fast Ignition of Fusion Targets; Hersonissos, Crete; Greece; 9 June 2008 through 13 June 2008. - 9781622763351 ; 32:2, s. 1126-1129
  • Conference paper (peer-reviewed)
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8.
  • Manduchi, G., et al. (author)
  • A universal access layer for the Integrated Tokamak Modelling Task Force
  • 2008
  • In: Fusion Engineering and Design. - : Elsevier BV. - 0920-3796. ; 83:2-3, s. 462-466
  • Journal article (peer-reviewed)abstract
    • The Integrated Tokamak Modelling (ITM) Task Force aims at providing a suite of codes for preparing and analyzing future ITER discharges. In the framework of the ITM, the universal access layer (UAL) provides the capability of storing and retrieving data involved in simulation. The underlying data structure is hierarchical and the granularity in data access is given by the definition of a set of consistent physical objects (CPOs). To describe the data structure of the overall ITM database, the XML schema description (XSD) has been used. Originally intended to describe the structure of XML documents, XSD is used here to provide an unambiguous way of describing how data are structured, regardless of the actual implementation of the underlying database.The MDSplus-based UAL implementation is currently under test and other prototypes for investigating alternative data storage systems are foreseen.
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9.
  • Brennan, M. T., et al. (author)
  • Impact of Oral Side Effects from Conditioning Therapy Before Hematopoietic Stem Cell Transplantation: Protocol for a Multicenter Study
  • 2018
  • In: Jmir Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 7:4
  • Journal article (peer-reviewed)abstract
    • Background: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens. Objective: The objectives of this prospective international observational multicenter study in hematopoietic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal relationship of oral complications related to conditioning regimens (chemotherapy with or without total body irradiation), stem cell transplantation and the immunologic reactions (mainly graft-vs-host-disease) that may follow, and to determine what subjective and objective oral complications related to treatment can predict negative clinical and economic outcomes and reduced quality of life. Methods: Adult patients at six study sites receiving full intensity conditioning, reduced intensity conditioning or nonmyeloablative conditioning, followed by autologous or allogeneic hematopoietic stem cell infusion, are included. A pre-treatment assessment includes medical conditions, planned chemo- and radiation therapy regimen, medications, allergies, social history, patient report of oral problems, dental history, subjective oral complaints, objective measures of oral conditions, current laboratory values, dental treatment recommended and untreated dental disease. Starting 1-3 days after hematopoietic stem cell infusion, a bedside assessment is completed 3 days per week until resolution of neutropenia. A patient questionnaire is also completed during hospitalization. Beyond this time, patients with continued oral mucositis or other oral problems are followed 1 day per week in an inpatient or outpatient setting. Additional visits for urgent care for acute oral problems after hospitalization are documented. Autologous transplant patients are being followed up at 100 days (SD 30 days) and at 1 year (SD 30 days) post-transplantation to identify any long-term side effects. Patients treated with allogeneic transplantation are being followed at 100 days (SD 30 days), 6 months (SD 30 days), and 12 months (SD 30 days). The follow-up assessments include cancer response to therapy, current medical conditions, medications, subjective and objective oral findings, quality of life measures and laboratory values. The targeted enrollment is 254 patients who have received HSCT. Results: A total of 260 participants have been enrolled, with 233 (91%) who have received HSCT. We anticipate enrollment of 20-30 additional participants to obtain the sample size of 254 enrolled participants who have received HSCT. Conclusions: The results of the ongoing prospective study will provide a unique dataset to understand the impact of oral complications on patients undergoing HSCT and provide needed evidence for guidelines regarding the management of this patient cohort.
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10.
  • Chapman, I.T., et al. (author)
  • Macroscopic Stability of High b MAST Plasmas
  • 2011
  • In: Nuclear Fusion. - 1741-4326 .- 0029-5515. ; 51, s. 073040-
  • Journal article (peer-reviewed)abstract
    • The high-beta capability of the spherical tokamak, coupled with a suite of world-leading diagnostics on MAST, has facilitated significant improvements in the understanding of performance-limiting core instabilities in high performance plasmas. For instance, the newly installed motional Stark effect diagnostic, with radial resolution
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11.
  • Chapman, I. T., et al. (author)
  • The physics of sawtooth stabilization
  • 2007
  • In: Plasma Physics and Controlled Fusion. - 0741-3335 .- 1361-6587. ; 49:12B, s. B385-B394
  • Journal article (peer-reviewed)abstract
    • Long period sawteeth have been observed to result in low-beta triggering of neo-classical tearing modes, which can significantly degrade plasma confinement. Consequently, a detailed physical understanding of sawtooth behaviour is critical, especially for ITER where fusion-born a particles are likely to lead to very long sawtooth periods. Many techniques have been developed to control, and in particular to destabilize the sawteeth. The application of counter-current neutral beam injection (NBI) in JET has resulted in shorter sawtooth periods than in Ohmic plasmas. This result has been explained because, firstly, the counter-passing fast ions give a destabilizing contribution to the n=1 internal kink mode-which is accepted to be related to sawtooth oscillations-and secondly, the flow shear strongly influences the stabilizing trapped particles. A similar experimental result has been observed in counter-NBI heated plasmas in MAST. However, the strong toroidal flows in spherical tokamaks mean that the sawtooth behaviour is determined by the gyroscopic flow stabilization of the kink mode rather than kinetic effects. In NBI heated plasmas in smaller conventional aspect-ratio tokamaks, such as TEXTOR, the flow and kinetic effects compete to give different sawtooth behaviour. Other techniques applied to destabilize sawteeth are the application of electron cyclotron current drive (ECCD) or ion cyclotron resonance heating (ICRH). In JET, it has been observed that localized ICRH is able to destabilize sawteeth which were otherwise stabilized by a co-existing population of energetic trapped ions in the core. This is explained through the dual role of the ICRH in reducing the critical magnetic shear required to trigger a sawtooth crash, and the increase in the local magnetic shear which results from driving current near the q=1 rational surface. Sawtooth control in ITER could be provided by a combination of ECCD and co-passing off-axis negative-NBI fast ions.
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12.
  • Guillerminet, B., et al. (author)
  • Integrated tokamak modelling: Infrastructure and Software Integration Project
  • 2008
  • In: Fusion Engineering and Design. - : Elsevier BV. - 0920-3796. ; 83:2-3, s. 442 - 447
  • Journal article (peer-reviewed)abstract
    • The Infrastructure and Software Integration Project must provide the hardware and software environment for the European integrated tokamak modelling taskforce to build and simulate a comprehensive fusion device. Several frameworks have been evaluated in 2006 and this paper reports on the current status of the gateway, the data communication system, the Web portal and the various ITM applications. The first version will be delivered in 2007, prefiguring the next decades' tools.
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13.
  • Pamela, S. J. P., et al. (author)
  • Simulation of ELMs in JET
  • 2010
  • In: 37th EPS Conference on Plasma Physics 2010, EPS 2010. - 9781622763313 ; , s. 53-56
  • Conference paper (peer-reviewed)
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15.
  • Bulthuis, Marjolein S., et al. (author)
  • Subjective Oral Dryness following Hematopoietic Cell Transplantation: A Report from the Orastem Study
  • 2024
  • In: TRANSPLANTATION AND CELLULAR THERAPY. - 2666-6375 .- 2666-6367. ; 30:4
  • Journal article (peer-reviewed)abstract
    • Xerostomia, or subjective oral dryness, is a serious complaint after hematopoietic cell transplantation (HCT). Xerostomia is rated as one of the most bothersome symptoms by HCT recipients, negatively affecting quality of life. This substudy of the Orastem study, prospective longitudinal, international, observational, multicenter study, aimed to describe the prevalence and severity of xerostomia following HCT. Furthermore, the effect of the conditioning regimen, type of transplantation, and oral mucosal changes related to chronic graft -versus -host disease (cGVHD) in the development of xerostomia were studied. All HCT recipients rated xerostomia on a scale of 0 to 10 before the conditioning regimen, several times early post-HCT, and at 3 months post-HCT, and only allogeneic HCT recipients also rated xerostomia at 6 and 12 months post-HCT. In addition, stimulated whole mouth saliva was collected several times. Linear regression models and longitudinal mixed-effects models were created to investigate the influence of indicators on xerostomia. A total of 99 autologous and 163 allogeneic HCT recipients were included from 6 study sites in Sweden, Canada, the Netherlands, and the United States. The prevalence of xerostomia was 40% before the conditioning regimen, 87% early post-HCT, and 64% at 3 months post-HCT. Complaints after autologous HCT were transient in nature, while the severity of xerostomia in allogeneic HCT recipients remained elevated at 12 months post-HCT. Compared to autologous HCT recipients, allogeneic HCT recipients experienced 1.0 point more xerostomia (95% confidence interval [CI], .1 to 2.0) early post-HCT and 1.7 points more (95% CI, .4 to 3.0) months post-HCT. Allogeneic HCT recipients receiving a high-intensity conditioning regimen experienced more xerostomia compared to those receiving a nonmyeloablative or reduced-intensity conditioning regimen. The difference was 2.0 points (95% CI, 1.1 to 2.9) early post-HCT, 1.8 points (95% CI, .3 to 3.3) after 3 months, and points (95% CI, .0 to 3.3) after 12 months. Total body irradiation as part of the conditioning regimen and oral mucosal changes related to cGVHD did not significantly influence the severity of xerostomia. Conditioning regimen intensity was a significant risk indicator in the development of xerostomia, whereas total body irradiation was not. Allogeneic HCT recipients experienced more xerostomia than autologous HCT recipients, a difference that cannot be explained by a reduction in stimulated salivary flow rate or the development of oral mucosal changes related to cGVHD.
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16.
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17.
  • Hender, T. C., et al. (author)
  • MHD stability with strongly reversed magnetic shear in JET
  • 2002
  • In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 44:7, s. 1143-1154
  • Journal article (peer-reviewed)abstract
    • Recent operation of JET with centrally strongly reversed magnetic shear, produced with the help of lower hybrid current drive, has extended the domain in which internal transport barriers (ITBs) can be formed in JET. Performance is frequently limited by magnetohydrodynamic (MHD) instabilities in these reversed shear regimes. The most severe limit is a pressure driven kink mode which leads to a disruption. This disruptive limit is essentially the same in ITB plasmas with low or strongly reversed shear. Unique to the reversed shear regime is a dominantly n = 1 mode, which has multiple harmonics. This mode is a seemingly common limit to performance, in the highest performance plasmas. Also unique to the reversed shear regime are q > 1 sawteeth events, which can in turn trigger n = 1 post-cursor oscillations. In general, these post-cursor oscillations are benign but do provide valuable information on the q-profile. Other instabilities, including 'snakes' at the outer q = 3 surface, are also observed to limit the performance of reversed magnetic shear ITB regimes.
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19.
  • Laheij, Amga, et al. (author)
  • Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients
  • 2019
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.
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20.
  • Nejadnik, M. Reza, et al. (author)
  • Self-healing Hybrid Nanocomposites consisting of Bisphosphonated Hyaluronan and Calcium Phosphate Nanoparticles
  • 2014
  • In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 35:25, s. 6918-6929
  • Journal article (peer-reviewed)abstract
    • Non-covalent interactions are often regarded as insufficient to construct macroscopic materials of substantial integrity and cohesion. However, the low binding energy of such reversible interactions can be compensated by increasing their number to work in concert to create strong materials. Here we present the successful development of an injectable, cohesive nanocomposite hydrogel based on reversible bonds between calcium phosphate nanoparticles and bisphosphonate-functionalized hyaluronic acid. These nanocomposites display a capacity for self-healing as well as adhesiveness to mineral surfaces such as enamel and hydroxyapatite. Most importantly, these non-covalently cross-linked composites are surprisingly robust yet biodegradable upon extensive in vitro and in vivo testing and show bone interactive capacity evidenced by bone ingrowth into material remnants. The herein presented method provides a new methodology for constructing nanoscale composites for biomedical applications, which owe their integrity to reversible bonds.
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21.
  • Nijs, Jo, et al. (author)
  • Nociceptive, neuropathic, or nociplastic low back pain? : The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations
  • 2024
  • In: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 6:3, s. e178-e188
  • Journal article (peer-reviewed)abstract
    • The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.
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22.
  • Skallsjö, Kristina, 1976, et al. (author)
  • Oral health in patients scheduled for hematopoietic stem cell transplantation in the Orastem study
  • 2023
  • In: Plos One. - 1932-6203. ; 18:5
  • Journal article (peer-reviewed)abstract
    • Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients >= 18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had >= one tooth with deep periodontal pockets, 147 (75.0%) had >= one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.
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23.
  • van Leeuwen, S. J. M., et al. (author)
  • Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation
  • 2021
  • In: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365.
  • Journal article (peer-reviewed)abstract
    • The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1x/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3x/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (>= 2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.
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24.
  • van Leeuwen, S. J. M., et al. (author)
  • The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach
  • 2023
  • In: Bmc Oral Health. - 1472-6831. ; 23:1
  • Journal article (peer-reviewed)abstract
    • BackgroundOral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score & GE; 2) or not (NON-OM).MethodsIn the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler.ResultsA different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis.ConclusionsThe salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively.
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