Purpose/Objective: Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy. Material and Methods: For 24 glioblastoma patients a photon- and proton-based dose escalation treatment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribution on this specific high dose region. Results: The median time between the planning MRI and additional MRI was 26 days (range 16–37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3–11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treatment plans, respectively. Conclusion: Our study showed that only for a limited number of patients anatomical changes during photon or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvolume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.
Abstract Background: We studied the relationship between trismus (maximum interincisor opening [MIO] ≤35 mm) and the dose to the ipsilateral masseter muscle (iMM) and ipsilateral medial pterygoid muscle (iMPM). Methods: Pretreatment and post-treatment measurement of MIO at 13 weeks revealed 17% of trismus cases in 83 patients treated with chemoradiation and intensity-modulated radiation therapy. Logistic regression models were fitted with dose parameters of the iMM and iMPM and baseline MIO (bMIO). A risk classification tree was generated to obtain optimal cut-off values and risk groups. Results: Dose levels of iMM and iMPM were highly correlated due to proximity. Both iMPM and iMM dose parameters were predictive for trismus, especially mean dose and intermediate dose volume parameters. Adding bMIO, significantly improved Normal Tissue Complication Probability (NTCP) models. Optimal cutoffs were 58 Gy (mean dose iMPM), 22 Gy (mean dose iMM) and 46 mm (bMIO). Conclusions: Both iMPM and iMM doses, as well as bMIO, are clinically relevant parameters for trismus prediction.
Background:In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19.Objective:Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19.Methods:This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand.Results:As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024.Conclusions:This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment.Trial Registration:ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359International Registered Report Identifier (IRRID):DERR1-10.2196/48183
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Worldwide over- and misuse of antibiotics has contributed to the development of antibiotic-resistance. The occurrence and increase of antibiotic-resistance is one of the most pressing global health care issues of the 21st century. Recently it has been recognized that fruit and flower anthocyanins have antimicrobial activity and thereby the potential to function as novel antibiotics. At the Hanze University of Applied Science, we were able to confirm the antimicrobial efficacy of purified Rosa and Tulipa anthocyanin extracts against an array of microbial species. Using our optimized extraction methods, anthocyanins can easily be extracted and purified from floral residual streams. Once marketed as novel antimicrobials, this valorization of residual streams to high-value compounds contributes to the transition towards a circular economy. However, for future application in different antimicrobial products, it is necessary to identify and characterize single antimicrobial anthocyanin molecules. Moreover, analysis of pilot-scale extraction- and fractionation-yields and antimicrobial bench-mark doses will provide information on their market and application potential. In the current project we propose to develop a strategy composed of fractionation and state-of-the-art characterization methods to identify anthocyanin-molecules with potent antimicrobial effects. To our knowledge this is the first strategy that combines in-depth chemical characterization of anthocyanins in relation to their antimicrobial efficacy. Once developed, this strategy will allow us to single out anthocyanin molecules with antimicrobial properties. The development of the proposed fractionation and characterization strategy is the first step towards the development of single anthocyanin molecules as novel plant-based antibiotics.
De besmetting van tulpenbollen door de agressieve schimmel, Fusarium oxysporum f.sp. tulpiae, ook wel zuur genoemd, is een grote zorg in de tulpenindustrie. Dit project, getiteld ?Fusarium besmetting van de tulp? richt zich op het ontwikkelen van producten en praktische richtlijnen voor kwekers, broeiers en exporteurs in de tulpenbranche, welke moeten resulteren in een sterke vermindering van aantasting van de tulp door de schimmel. Het hiervoor benodigde onderzoek staat onder leiding van het lectoraat Innovatieve Moleculaire Diagnostiek en het Centre of Expertise Generade van de Hogeschool Leiden. In het project participeren kennisinstellingen, MKB-bedrijven uit de tulpenbranche en bedrijven met een specifieke expertise op gebied van gewasbescherming en Genomics. Het project bestaat uit vier deelonderzoeken: 1. Een inventarisatie van de risicofactoren op infectie van de tulp dient als basis van het project. Dit levert een goed uitgangspunt voor onderzoek naar de interactie tussen Fusarium als gast, de tulpenbol als gastheer en de bodem als omgevingsfactor. Ten behoeve van de inventarisatie zal een kwantitatieve diagnostische test worden ontwikkeld voor het aantonen van Fusarium in de bodem, in water, in lucht en in de tulpenbol zelf zodat kan worden aangetoond waar in de keten het risico op verspreiding van de schimmel aanwezig is. 2. Het Fusarium onderzoek zal zich richten op genetische factoren die bepalend zijn voor de virulentie ofwel de ziekteverwekkende eigenschappen van de schimmel die specifiek gericht zijn tegen de tulp. Dit zal gebeuren met behulp van Next Generation Sequencing. 3. Daarnaast richt het onderzoek zich op mogelijkheden ter bescherming van de tulpenbol tijdens verschillende handelingen (vooral tijdens en na het rooiproces). Er wordt nagegaan wat het effect is van coating van de tulpenbol met antagonisten die een afweerfunctie tegen Fusarium hebben. 4. Op dit moment wordt veelal gebruik gemaakt van agressieve chemische middelen om de grond te ontsmetten voordat de tulpenbollen worden geplant. Deze behandeling is niet of nauwelijks effectief tegen Fusarium. Een vierde pijler van het onderzoek zal daarom gericht zijn op de verbetering van de bodem. Doormiddel van de analyse van het effect van de aanwezigheid van antagonisten in de bodem wordt nagegaan of dit bescherming kan bieden tegen Fusarium besmetting van de tulp.
Virtual Reality Exposure Therapie (VRET) is een innovatie die ervoor kan zorgen dat behandelingen van angststoornissen efficiënter en effectiever worden. Het verschil met de huidige exposure therapie is dat cliënten door middel van virtual reality worden blootgesteld aan angstige situaties, in plaats van in werkelijkheid. Hierdoor kan de exposure worden gedoseerd en geregisseerd in aanwezigheid van de therapeut. Moovd, een bedrijf dat toegevoegde waarde creëert met virtuele technologieën, wil met deze subsidieaanvraag een VR-toepassing creëren voor de behandeling van PTSS. Inclusief wetenschappelijk bewijs en onderzoek naar de commerciële haalbaarheid. Het onderzoek wordt uitgevoerd in samenwerking met Psychotrauma Expertise Centrum PSYTREC.
