Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers. Methods: For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results: Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some proinflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Conclusion: Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
Purpose: Exercise therapy with a focus on muscle strengthening has proven to be effective for the management of knee osteoarthritis (OA). Yet it is not known whether high-intensity resistance training (RT) is more effective in improving upper leg muscle strength and physical performance than low-intensity RT. Still, there is some controversy regarding the effectiveness of high-intensity RT and whether or not it is harmful, for instance by accelerating cartilage degeneration, osteophyte formation, or increasing synovitis. Any catabolic or anabolic response of musculoskeletal tissue to RT might first be visible on a biochemical level before changes in clinical symptoms are measurable. Serum biomarkers can objectively measure early biochemical changes and assess whether RT leads to a more anabolic or catabolic response. The aim of this study is to assess (i) whether high-intensity RT elicits a different response (e.g. catabolic) on systemic inflammation and musculoskeletal tissues in and surrounding the joint, including bone, cartilage, muscle, and synovial tissue compared to low-intensity RT; and (ii) whether there is an association between changes in serum levels of inflammatory and musculoskeletal tissue-derived biomarkers and improvements in clinical outcomes (performance-based tests and self-reported outcomes on pain and activity limitations).Methods: In a randomized controlled trial, 177 participants with knee OA conducted a high-intensity (70%-80% of the Repetition Maximum (1RM)) or low-intensity (40%-50% 1RM) RT program 3 times a week for 12 weeks. Measures of clinical outcomes and serum samples were collected at the start of RT (pre-intervention), after 3 months at the end of RT (post-intervention), and 6 months after RT (follow-up). As a reflection of systemic inflammation (CRP), synovitis (CRPM, C3M), bone turnover (OC, CTX-I), cartilage turnover (PRO-C2, C2M, huARGS), muscle turnover (PRO-C3, PRO-C6), and cell behaviour (col10neo) a total of eleven serum biomarkers were analysed. With the exception of CRP, which was determined with an immunoturbidimetric assay, ELISA assays were used to quantify serum levels of the other 10 serum biomarkers. The primary outcome measures are the changes in serum biomarker levels. Other outcome measures include upper leg muscle strength, performance-based tests, and self-reported outcomes on pain and activity limitations.Results: High-intensity RT resulted in greater improvements in muscle strength compared to low-intensity RT when measured by the estimated 1RM. No significant differences between groups were found for upper leg muscle strength (Nm/kg) when measured with an isokinetic dynamometer. Both groups showed similar improvements in pain and physical functioning. Although there is no difference between groups in clinical outcomes, except for the estimated 1RM, we expect that participants in the high-intensity RT group are more likely to have enhanced serum levels of catabolic biomarkers than participants in the low-intensity RT group. Since both the high-intensity RT group and low-intensity RT group improved over time, we expect that changes in serum biomarker levels are associated with overall improvements in clinical outcomes. Almost all participants had normal CRP values (<10 mg/L) at baseline. No significant differences between the intensity RT groups in CRP levels at baseline, at 3 months, and 6 months were found. In both groups, there was no evidence that RT influenced CRP serum levels.Conclusions: The work to date on CRP serum levels suggests that RT did not influence CRP levels. This result may be explained by the high percentage of participants with normal CRP levels (<10 mg/L). We are currently in the process of analyzing the remaining 10 neo-epitope biomarkers. We expect that our remaining 10 assays have the potential to measure changes in serum biomarker levels in response to RT. This will be the first study to investigate the effects of high-intensity versus low-intensity RT on musculoskeletal tissue turnover in individuals with knee OA. With this, we aim to determine whether high-intensity RT can improve upper leg muscle strength and physical performance without worsening systemic inflammation or causing adverse effects on musculoskeletal knee OA-related tissues.
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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Achtergrond: Chronische pijn is een veelvoorkomend probleem. Hulpverleners hebben behoefte aan handvatten om de hulp aan mensen met chronische pjjn te verbeteren. Huidige behandelingen sorteren beperkt effect en de waardering van mensen over de ontvangen zorg is matig. Het faciliteren van betrokkenheid en eigen regie zijn voorwaardelijk voor effectieve hulp. EHealth toepassingen inclusief het monitoren van objectieve biomarkers voor pijn kunnen hierbij behulpzaam zijn. Een bestaande EHealth toepassing gericht op het informeren van mensen met een chronische aandoening en het faciliteren van zelfmanagement is beschikbaar. Doelstelling: 1)Het doorontwikkelen van een bestaande EHealth toepassing specifiek voor mensen met chronische pijn en het evalueren van biomarkers. 2)De ontwikkelde EHealth toepassing inclusief biomarkeranalyse te implementeren bij een beperkte groep van mensen met chronische musculoskeletale pijn om eerste effecten te evalueren en gebruikerservaringen te inventariseren en 3)op basis van de verkregen resultaten een vervolg onderzoeksaanvraag te schrijven om de effecten van deze nieuwe behandelwijze te onderzoeken en nieuwe biomarker-testen te ontwikkelen. Vraagstellingen: 1)Hoe ziet de doorontwikkeling (op basis van co-creatie) van de EHealth toepassing er concreet uit? 2)Is de biomarker α-amylase een objectieve maat voor pijnintensiteit? 3)Wat zijn de eerste effecten van deze EHealth applicatie? (uitkomstmaten zijn pijn, α-amylase concentratie, dagelijks functioneren en kwaliteit van leven) 4)Wat zijn de ervaringen van gebruikers (patiënten en hulpverleners)? Aanpak: Het onderzoek wordt uitgevoerd door een consortium van deskundigen op het gebied van niet-farmaceutische behandeling van mensen met chronische pijn en zelfmanagement, de ontwikkeling en het gebruik van biomarkers voor chronische pijn, een EHealth ontwikkelaar en behandelaren van mensen met chronische pijn en patiënten. Een EHealth toepassing wordt ontwikkeld, biomarkers waaronder α-amylase worden geëvalueerd en de eerste effecten en gebruikerservaringen van deze interventie inclusief biomarkerbepaling worden gemonitord in een populatie van mensen met chronische lage rug en/of nekpijn.
Sensoren gebaseerd op nanotechnologie worden beschouwd als een technologie die sterk kan bijdragen aan de kwaliteit van de gezondheidszorg en aan het verminderen van de zorgkosten. Door hun extreme gevoeligheid zijn dit type sensoren in staat om met kleine monstervolumes in korte tijd een nauwkeurige diagnose te kunnen stellen op basis van bijvoorbeeld bloed-, speeksel-, adem- of urinemonsters. Concreet betekent dit dat met dit type sensoren eenvoudige analyses mogelijk zijn, waardoor er extra mogelijkheden naast bestaande, vaak uitgebreide, analyselaboratoria ontstaan. Hoewel er een divers aantal sensorprincipes beschikbaar is, zijn er tot op heden nog nauwelijks praktische toepassingen gerealiseerd. De reden is dat er nog een aantal technische stappen te zetten zijn om van een laboratorium-prototype sensor tot een compleet analyse-apparaat te komen. Binnen het huidige project willen de consortiumpartners deze ontwikkeling uitvoeren voor een optische nanosensor, waarbij wordt voortgebouwd op de kennis en ervaring die binnen het lectoraat NanoPhysics Interface is opgedaan in de afgelopen twee jaren. Specifiek zal worden gekeken naar twee belangrijke aspecten: het aanbrengen van de gevoelige laag en de elektronische interface. Belangrijke aspecten hierbij zijn dat de gevoelige laag (die een interactie heeft met de op te sporen stoffen) lokaal op de juiste plek op de sensor wordt aangebracht en een goede hechting vertoont. Voor sommige toepassingen kan het tevens nodig zijn dat er verschillende gevoelige lagen op een chip (met meerdere sensoren) gecombineerd kunnen worden. Voor de uitlees-elektronica zal met name gekeken worden naar de optische aansluiting op de chip (die eenvoudig te vervangen moet zijn), naar mogelijkheden tot miniaturisatie (om de meting zo flexibel mogelijk te kunnen inzetten) en naar de eisen aan de gebruikersinterface (afhankelijk van de toepassing en de doelgroep). Uiteindelijk is het de bedoeling dat het geheel samengevoegd wordt in een demonstrator-opstelling. Vanwege de huidige kennis binnen het lectoraat op het gebied van metingen aan het menselijk metabolisme via biomarkers op de huid, is ervoor gekozen om deze toepassing voor de demonstrator te gebruiken.
Point-of-Care devices are broadly viewed as an important contribution to reduce the costs in our healthcare system. Cheap, quick, and reliable testing close to the point of need, can help early detection and thus reduce treatment costs, while improving the quality of life. An important challenge in the realization is the development of the individual cartridges that should be produced in large quantities at low costs. Especially for applications where high sensitivity is required, these cartrgidges will typically have a complex design. In this project we want to develop a manufacturing strategy for large scale production of cartridges based on photonic sensing chips, currently the most sensitive sensors available. A typical sensor cartridge with photonic sensors would comprise the sensor chip, an interface with active components (light source and detectors), the bio-active layer that captures the biomarkers to be detected and a protective package. In addition, there is the choice to integrate the active components in the package (making the interface an electrical one) or placing them in the read-out unit (making the interface an optical one). Finally, testing of the sensor cartridges should also be part of the process. A suitable manufacturing strategy would offer the lowest total-cost-of-ownership (TCO) of the production and use of the cartrdiges. Important in the considereations is that steps can be carried out at the wafer level, at the die level, and at the cartridge level. Because choices for a specific solution will strongly influence the possibilities for other steps, the development of a producitons strategy is far from straightforward. In this project we want to study the possibilities of the individual processes at the three levels mentioned (wafer, die, and cartridge), and in parallel develop a theoretical framework for finding the best strategy in this type of complex production processes.
