3,300 results on '"Koopman"'
Search Results
2. Reply - Letter to the editor entitled "Letter to editor - Dietary and lifestyle inflammation scores in relation to colorectal cancer recurrence and all-cause mortality: A longitudinal analysis".
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Wesselink E, Boshuizen HC, van Lanen AS, Kok DE, Derksen JWG, Smit KC, de Wilt JHW, Koopman M, May AM, Kampman E, and van Duijnhoven FJB
- Abstract
Competing Interests: Conflict of interest All authors declare no conflicts of interest.
- Published
- 2024
- Full Text
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3. Reducing behavior problems in children born after an unintended pregnancy: the generation R study.
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Enthoven CA, Labrecque JA, Koopman-Verhoeff ME, Lambregtse-van den Berg MP, Hillegers MHJ, El Marroun H, and Jansen PW
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- Humans, Female, Pregnancy, Netherlands epidemiology, Child, Adolescent, Male, Adult, Child, Preschool, Infant, Child Behavior Disorders psychology, Mothers psychology, Birth Cohort, Child Behavior psychology, Intention, Social Support, Pregnancy, Unplanned psychology, Problem Behavior psychology, Depression, Postpartum psychology, Depression, Postpartum prevention & control
- Abstract
Objectives: To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth., Methods: Data from the Generation R Study were used, a population-based birth cohort in Rotterdam, the Netherlands (N = 9621). Differences in child internalizing and externalizing behavior at ages 1.5, 3, 6, 9 and 13 years between pregnancy intention groups were estimated using linear regression. Associations of postnatal depression and social support with internalizing and externalizing problems were also estimated using linear regression. Child behavior outcomes where compared before and after modelling a situation in which none of the mothers experienced a postnatal depression and all mother experienced high social support., Results: Most pregnancies (72.9%) were planned, 14.8% were unplanned and wanted, 10.8% were unplanned with initially ambivalent feelings and 1.5% with prolonged ambivalent feelings. Children from unplanned pregnancies had more internalizing and externalizing problems at all ages as compared to children from a planned pregnancy, especially when ambivalent feelings were present. Hypothetically eliminating on postnatal depression reduced the differences in internalizing and externalizing problems by 0.02 to 0.16 standard deviation. Hypothetically increasing social support did not significantly reduce the difference in internalizing and externalizing problems., Conclusions: Children from an unplanned pregnancy have more behavior problems, in particular when mothers had prolonged ambivalent feelings. Eliminating postnatal depression may help to reduce the inequality in child behavior related to pregnancy intention., (© 2024. The Author(s).)
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- 2024
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4. Post-translational modifications of vertebrate striated muscle myosin heavy chains.
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Morales PN, Coons AN, Koopman AJ, Patel S, Chase PB, Parvatiyar MS, and Pinto JR
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- Animals, Humans, Muscle, Striated metabolism, Vertebrates metabolism, Protein Processing, Post-Translational, Myosin Heavy Chains metabolism
- Abstract
Post-translational modifications (PTMs) play a crucial role in regulating the function of many sarcomeric proteins, including myosin. Myosins comprise a family of motor proteins that play fundamental roles in cell motility in general and muscle contraction in particular. A myosin molecule consists of two myosin heavy chains (MyHCs) and two pairs of myosin light chains (MLCs); two MLCs are associated with the neck region of each MyHC's N-terminal head domain, while the two MyHC C-terminal tails form a coiled-coil that polymerizes with other MyHCs to form the thick filament backbone. Myosin undergoes extensive PTMs, and dysregulation of these PTMs may lead to abnormal muscle function and contribute to the development of myopathies and cardiovascular disorders. Recent studies have uncovered the significance of PTMs in regulating MyHC function and showed how these PTMs may provide additional modulation of contractile processes. Here, we discuss MyHC PTMs that have been biochemically and/or functionally studied in mammals' and rodents' striated muscle. We have identified hotspots or specific regions in three isoforms of myosin (MYH2, MYH6, and MYH7) where the prevalence of PTMs is more frequent and could potentially play a significant role in fine-tuning the activity of these proteins., (© 2024 Wiley Periodicals LLC.)
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- 2024
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5. Safety and Efficacy of Immunization with a Late-Liver-Stage Attenuated Malaria Parasite.
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Lamers OAC, Franke-Fayard BMD, Koopman JPR, Roozen GVT, Janse JJ, Chevalley-Maurel SC, Geurten FJA, de Bes-Roeleveld HM, Iliopoulou E, Colstrup E, Wessels E, van Gemert GJ, van de Vegte-Bolmer M, Graumans W, Stoter TR, Mordmüller BG, Houlder EL, Bousema T, Murugan R, McCall MBB, Janse CJ, and Roestenberg M
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- Adult, Animals, Female, Humans, Male, Young Adult, Antibodies, Protozoan blood, Antibodies, Protozoan immunology, Double-Blind Method, Liver parasitology, Liver immunology, Healthy Volunteers, Malaria Vaccines adverse effects, Malaria Vaccines immunology, Malaria Vaccines administration & dosage, Malaria, Falciparum blood, Malaria, Falciparum immunology, Malaria, Falciparum parasitology, Malaria, Falciparum prevention & control, Parasitemia blood, Parasitemia immunology, Parasitemia parasitology, Parasitemia prevention & control, Plasmodium falciparum genetics, Plasmodium falciparum immunology, Sporozoites genetics, Sporozoites immunology, Vaccines, Attenuated adverse effects, Vaccines, Attenuated immunology, Vaccines, Attenuated administration & dosage
- Abstract
Background: Currently licensed and approved malaria subunit vaccines provide modest, short-lived protection against malaria. Immunization with live-attenuated Plasmodium falciparum malaria parasites is an alternative vaccination strategy that has potential to improve protection., Methods: We conducted a double-blind, controlled clinical trial to evaluate the safety, side-effect profile, and efficacy of immunization, by means of mosquito bites, with a second-generation genetically attenuated parasite (GA2) - a mei2 single knockout P. falciparum NF54 parasite (sporozoite form) with extended development into the liver stage. After an open-label dose-escalation safety phase in which participants were exposed to the bites of 15 or 50 infected mosquitoes (stage A), healthy adults who had not had malaria were randomly assigned to be exposed to 50 mosquito bites per immunization of GA2, an early-arresting parasite (GA1), or placebo (bites from uninfected mosquitoes) (stage B). After the completion of three immunization sessions with 50 mosquito bites per session, we compared the protective efficacy of GA2 against homologous P. falciparum controlled human malaria infection with that of GA1 and placebo. The primary end points were the number and severity of adverse events (in stages A and B) and blood-stage parasitemia greater than 100 P. falciparum parasites per milliliter after bites from GA2-infected mosquitoes (in stage A) and after controlled human malaria infection (in stage B)., Results: Adverse events were similar across the trial groups. Protective efficacy against subsequent controlled human malaria infection was observed in 8 of 9 participants (89%) in the GA2 group, in 1 of 8 participants (13%) in the GA1 group, and in 0 of 3 participants in the placebo group. A significantly higher frequency of P. falciparum -specific polyfunctional CD4+ and Vδ2+ γδ T cells were observed among participants who received GA2 than among those who received GA1, whereas GA2 and GA1 induced similar antibody titers targeting the P. falciparum circumsporozoite protein., Conclusions: In this small trial, GA2 was associated with a favorable immune induction profile and protective efficacy, findings that warrant further evaluation. (Funded by the Bontius Foundation; ClinicalTrials.gov number, NCT04577066.)., (Copyright © 2024 Massachusetts Medical Society.)
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- 2024
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6. Electrical impedance tomography monitoring in adult ICU patients: state-of-the-art, recommendations for standardized acquisition, processing, and clinical use, and future directions.
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Scaramuzzo G, Pavlovsky B, Adler A, Baccinelli W, Bodor DL, Damiani LF, Franchineau G, Francovich J, Frerichs I, Giralt JAS, Grychtol B, He H, Katira BH, Koopman AA, Leonhardt S, Menga LS, Mousa A, Pellegrini M, Piraino T, Priani P, Somhorst P, Spinelli E, Händel C, Suárez-Sipmann F, Wisse JJ, Becher T, and Jonkman AH
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- Adult, Humans, Critical Illness therapy, Respiration, Artificial standards, Respiration, Artificial methods, Electric Impedance, Intensive Care Units organization & administration, Monitoring, Physiologic methods, Monitoring, Physiologic standards, Monitoring, Physiologic trends, Tomography methods, Tomography standards, Tomography trends
- Abstract
Electrical impedance tomography (EIT) is an emerging technology for the non-invasive monitoring of regional distribution of ventilation and perfusion, offering real-time and continuous data that can greatly enhance our understanding and management of various respiratory conditions and lung perfusion. Its application may be especially beneficial for critically ill mechanically ventilated patients. Despite its potential, clear evidence of clinical benefits is still lacking, in part due to a lack of standardization and transparent reporting, which is essential for ensuring reproducible research and enhancing the use of EIT for personalized mechanical ventilation. This report is the result of a four-day expert meeting where we aimed to promote the consistent and reliable use of EIT, facilitating its integration into both clinical practice and research, focusing on the adult intensive care patient. We discuss the state-of-the-art regarding EIT acquisition and processing, applications during controlled ventilation and spontaneous breathing, ventilation-perfusion assessment, and novel future directions., Competing Interests: Declarations Ethical approval and consent for participate Not applicable. Consent for publication Not applicable. Competing interests LSM is supported by a fellowship from the European Respiratory Society and a scholarship from Canadian Lung Society. SL has received EIT-related research funding under grant LE 817/40–1 (Project No. 422367304, paid to the institution) from German Research Foundation (DFG). AJ is supported by a personal grant from NWO (ZonMw Veni 2022, 09150162210061, paid to the institution) and has received research funding (paid to the institution) from Pulmotech B.V., Liberate Medical, Netherlands eScience Center and Health ~ Holland. All other authors declared that they have no competing interests., (© 2024. The Author(s).)
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- 2024
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7. Reply - Letter to the editor entitled "Letter to editor regarding Dietary and lifestyle inflammation scores in relation to colorectal cancer recurrence and all-cause mortality: A longitudinal analysis".
- Author
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Wesselink E, Boshuizen HC, van Lanen AS, Kok DE, Derksen JWG, Smit KC, de Wilt JHW, Koopman M, May AM, Kampman E, and van Duijnhoven FJB
- Abstract
Competing Interests: Conflict of interest All authors declare no conflicts of interest.
- Published
- 2024
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8. A wearable gait lab powered by sensor-driven digital twins for quantitative biomechanical analysis post-stroke.
- Author
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Simonetti D, Hendriks M, Koopman B, Keijsers N, and Sartori M
- Abstract
Commonly, quantitative gait analysis post-stroke is performed in fully equipped laboratories housing costly technologies for quantitative evaluation of a patient's movement capacity. Combining such technologies with an electromyography (EMG)-driven musculoskeletal model can estimate muscle force properties non-invasively, offering clinicians insights into motor impairment mechanisms. However, lab-constrained areas and time-demanding sensor setup and data processing limit the practicality of these technologies in routine clinical care. We presented wearable technology featuring a multi-channel EMG-sensorized garment and an automated muscle localization technique. This allows unsupervised computation of muscle-specific activations, combined with five inertial measurement units (IMUs) for assessing joint kinematics and kinetics during various walking speeds. Finally, the wearable system was combined with a person-specific EMG-driven musculoskeletal model (referred to as human digital twins), enabling the quantitative assessment of movement capacity at a muscle-tendon level. This human digital twin facilitates the estimation of ankle dorsi-plantar flexion torque resulting from individual muscle-tendon forces. Results demonstrate the wearable technology's capability to extract joint kinematics and kinetics. When combined with EMG signals to drive a musculoskeletal model, it yields reasonable estimates of ankle dorsi-plantar flexion torques ( R
2 = 0.65 ± 0.21) across different walking speeds for post-stroke individuals. Notably, EMG signals revealing an individual's control strategy compensate for inaccuracies in IMU-derived kinetics and kinematics when input into a musculoskeletal model. Our proposed wearable technology holds promise for estimating muscle kinetics and resulting joint torque in time-limited and space-constrained environments. It represents a crucial step toward translating human movement biomechanics outside of controlled lab environments for effective motor impairment monitoring., Competing Interests: The authors declare no competing interests exist., (© The Author(s) 2024.)- Published
- 2024
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9. Innovative Complementary Cooling Intervention for Women's Multiple Sclerosis Symptoms: A Mixed-Methods Study.
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Colsch R, Guthrie PF, Koopman ML, and Rippie S
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Purpose: This mixed-methods study examined the relationship between multiple sclerosis symptoms to perceived severity, frequency of Uhthoff's phenomenon, the effectiveness of complementary cooling therapy on women's symptom clusters, and quality of life. This study explored the experiences of women with multiple sclerosis when using the Opal Cool Wrap related to heat intolerance, a complementary alternative therapy. Methods: Quantitative analysis of results from surveys from 62 women and seven qualitative semi-structured interviews with a subset of women who completed the surveys validated and illustrated the quantitative findings. Findings: Significant improvement in perceived severity for health transition, physical functioning, role-physical, bodily pain, and social functioning based on pre-/post-cooling therapy use. Three themes emerged from seven interviews: (1) being overheated impacts the quality of life; (2) cool wrap, a helpful tool for managing heat symptoms; and (3) strategies to remain cool. Conclusion: This study provides a comprehensive mixed-methods lens on the unique challenges women with multiple sclerosis face and information for disease management. Heat-related multiple sclerosis symptom clusters and Uhthoff's phenomenon women experience are common and impact safety, independence, health, and quality of life. Identifying complementary strategies such as cool showers and a cooling device to prevent and manage heat-related symptoms is a priority.
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- 2024
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10. A review of migratory Alosidae marine ecology in the northwest Atlantic.
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Brown CR, Sergio AJA, Bate CS, Koopman N, Roland JB, Notman-Grobler ODP, Mastrodimitropoulos PMB, Piczak ML, and Lennox RJ
- Abstract
Migratory animals play a crucial role in connecting distinct habitats by transferring matter and energy across ecosystem boundaries. In the North Atlantic, anadromous species exemplify this through their movement between freshwater and marine environments. Alosids, including species such as alewife (Alosa pseudoharengus), blueback herring (Alosa aestivalis), and American shad (Alosa sapidissima), exhibit this migratory behavior to maximize growth and fecundity and are, therefore, vital components of Atlantic coastal ecosystems. Despite their ecological importance, these species have experienced considerable population declines. Due to a research focus on dams and the freshwater phase of their ecology, the marine ecology of Alosids remains much less understood, potentially hindering effective management. This paper synthesizes current knowledge on the marine ecology of anadromous alewife, blueback herring, and American shad in the northwest Atlantic, focusing on life-history aspects, migratory patterns, and foraging behavior at sea. The paper also outlines current fisheries management and the anthropogenic threats these species face during their marine phase. We identified knowledge gaps regarding marine distribution, migration routes, impacts of climate change on movement and behavior, population dynamics, and the identification of gaspereau. By identifying gaps in the literature, we highlight research needs, emphasizing the role of telemetry studies in tracking marine movements and the impact of climate change on habitat use. Addressing these gaps through targeted research on marine ecology and movement patterns is essential for developing informed management strategies aimed at increasing Alosid populations., (© 2024 The Author(s). Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)
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- 2024
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11. Development of a prediction model for clinically-relevant fatigue: a multi-cancer approach.
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Adiprakoso D, Katsimpokis D, Oerlemans S, Ezendam NPM, van Maaren MC, van Til JA, van der Heijden TGW, Mols F, Aben KKH, Vink GR, Koopman M, van de Poll-Franse LV, and de Rooij BH
- Abstract
Purpose: Fatigue is the most prevalent symptom across cancer types. To support clinicians in providing fatigue-related supportive care, this study aims to develop and compare models predicting clinically relevant fatigue (CRF) occurring between two and three years after diagnosis, and to assess the validity of the best-performing model across diverse cancer populations., Methods: Patients with non-metastatic bladder, colorectal, endometrial, ovarian, or prostate cancer who completed a questionnaire within three months after diagnosis and a subsequent questionnaire between two and three years thereafter, were included. Predictor variables included clinical, socio-demographic, and patient-reported variables. The outcome was CRF (EORTC QLQC30 fatigue ≥ 39). Logistic regression using LASSO selection was compared to more advanced Machine Learning (ML) based models, including Extreme gradient boosting (XGBoost), support vector machines (SVM), and artificial neural networks (ANN). Internal-external cross-validation was conducted on the best-performing model., Results: 3160 patients were included. The logistic regression model had the highest C-statistic (0.77) and balanced accuracy (0.65), both indicating good discrimination between patients with and without CRF. However, sensitivity was low across all models (0.22-0.37). Following internal-external validation, performance across cancer types was consistent (C-statistics 0.73-0.82)., Conclusion: Although the models' discrimination was good, the low balanced accuracy and poor calibration in the presence of CRF indicates a relatively high likelihood of underdiagnosis of future CRF. Yet, the clinical applicability of the model remains uncertain. The logistic regression performed better than the ML-based models and was robust across cohorts, suggesting an advantage of simpler models to predict CRF., (© 2024. The Author(s).)
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- 2024
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12. Reply to Letter to the Editor "Optimising Treatment Strategies in Metastatic Colorectal Cancer: Insights from CAIRO4" by Güzel et al.
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de Wilt JHW, van der Kruijssen DEW, and Koopman M
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- 2024
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13. Mitochondrial Nicotinamide Nucleotide Transhydrogenase: Role in Energy Metabolism, Redox Homeostasis, and Cancer.
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Gan Z, van der Stelt I, Li W, Hu L, Song J, Grefte S, van de Westerlo E, Zhang D, van Schothorst EM, Claahsen-van der Grinten HL, Teerds KJ, Adjobo-Hermans MJW, Keijer J, and Koopman WJH
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- Animals, Humans, Mice, NADP Transhydrogenase, AB-Specific metabolism, NADP Transhydrogenase, AB-Specific genetics, Neoplasms metabolism, Neoplasms genetics, Neoplasms pathology, Oxidation-Reduction, Mitochondria metabolism, NADP Transhydrogenases metabolism, NADP Transhydrogenases genetics, Homeostasis, Energy Metabolism
- Abstract
Significance: Dimeric nicotinamide nucleotide transhydrogenase (NNT) is embedded in the mitochondrial inner membrane and couples the conversion of NADP
+ /NADH into NADPH/NAD+ to mitochondrial matrix proton influx. NNT was implied in various cancers, but its physiological role and regulation still remain incompletely understood. Recent Advances: NNT function was analyzed by studying: (1) NNT gene mutations in human (adrenal) glucocorticoid deficiency 4 (GCCD4), (2) Nnt gene mutation in C57BL/6J mice, and (3) the effect of NNT knockdown/overexpression in (cancer) cells. In these three models, altered NNT function induced both common and differential aberrations. Critical Issues: Information on NNT protein expression in GCCD4 patients is still scarce. Moreover, NNT expression levels are tissue-specific in humans and mice and the functional consequences of NNT deficiency strongly depend on experimental conditions. In addition, data from intact cells and isolated mitochondria are often unsuited for direct comparison. This prevents a proper understanding of NNT-linked (patho)physiology in GCCD4 patients, C57BL/6J mice, and cancer (cell) models, which complicates translational comparison. Future Directions: Development of mice with conditional NNT deletion, cell-reprogramming-based adrenal (organoid) models harboring specific NNT mutations, and/or NNT-specific chemical inhibitors/activators would be useful. Moreover, live-cell analysis of NNT substrate levels and mitochondrial/cellular functioning with fluorescent reporter molecules might provide novel insights into the conditions under which NNT is active and how this activity links to other metabolic and signaling pathways. This would also allow a better dissection of local signaling and/or compartment-specific ( i.e., mitochondrial matrix, cytosol, nucleus) effects of NNT (dys)function in a cellular context. Antioxid. Redox Signal. 41, 927-956.- Published
- 2024
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14. Molecular Tumor Board of the University Medical Center Groningen (UMCG-MTB): outcome of patients with rare or complex mutational profiles receiving MTB-advised targeted therapy.
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de Jager VD, Plomp P, Paats MS, van Helvert S, Elst AT, van den Berg A, Dubbink HJ, van Geffen WH, Zhang L, Hendriks LEL, Hiltermann TJN, Hiddinga BI, Hijmering-Kappelle LBM, Jalving M, Kluiver J, Koopman B, van Kruchten M, van der Logt EMJ, Piet B, van Putten J, Reitsma BH, Rutgers SR, de Vries M, Stigt JA, Groves MR, Timens W, Willems SM, van Kempen LC, Schuuring E, and van der Wekken AJ
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Academic Medical Centers, Follow-Up Studies, Adult, Treatment Outcome, Aged, 80 and over, Neoplasms drug therapy, Neoplasms genetics, Mutation, Molecular Targeted Therapy methods
- Abstract
Purpose: Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning. The objective of this study was to determine the effectiveness of MTB treatment recommendations for patients with rare and complex mutational profiles as implemented in the MTB of the University Medical Center Groningen (UMCG-MTB) in 2019-2020., Patients and Methods: A retrospective follow-up study was carried out to determine the clinical outcome of patients with uncommon or rare (combinations of) molecular aberrations for whom targeted therapy was recommended as the next line of treatment by the UMCG-MTB in 2019 and 2020., Results: The UMCG-MTB recommended targeted therapy as the next line of treatment in 132 of 327 patients: 37 in clinical trials, 67 in the on-label setting, and 28 in the off-label setting. For on- and off-label treatment recommendations, congruence of recommended and received treatment was 85% in patients with available follow-up (67/79). Treatment with on-label therapy resulted in a response rate of 50% (21/42), a median progression-free survival (PFS) of 6.3 months [interquartile range (IQR) 2.9-14.9 months], and median overall survival (OS) of 15.8 months (IQR 6.4-34.2 months). Treatment with off-label therapy resulted in a response rate of 53% (8/15), a median PFS of 5.1 months (IQR 1.9-7.3 months), and a median OS of 17.7 months (IQR 5.1-23.7 months)., Conclusion: Treatment with MTB-recommended next-line targeted therapy for patients with often heavily pretreated cancer with rare and complex mutational profiles resulted in positive overall responses in over half of patients. Off-label use of targeted therapies, for which there is sufficient rationale as determined by an MTB, is an effective treatment strategy. This study underlines the relevance of discussing patients with rare and complex mutational profiles in an MTB., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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15. ISTA Award 2023: Toward functional reconstruction of the pre-diseased state in total knee arthroplasty.
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Tzanetis P, Fluit R, de Souza K, Robertson S, Koopman B, and Verdonschot N
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- Humans, Biomechanical Phenomena, Male, Female, Aged, Robotic Surgical Procedures methods, Knee Prosthesis, Middle Aged, Tomography, X-Ray Computed, Knee Joint surgery, Knee Joint physiopathology, Arthroplasty, Replacement, Knee methods, Osteoarthritis, Knee surgery, Osteoarthritis, Knee physiopathology, Awards and Prizes
- Abstract
Aims: The surgical target for optimal implant positioning in robotic-assisted total knee arthroplasty remains the subject of ongoing discussion. One of the proposed targets is to recreate the knee's functional behaviour as per its pre-diseased state. The aim of this study was to optimize implant positioning, starting from mechanical alignment (MA), toward restoring the pre-diseased status, including ligament strain and kinematic patterns, in a patient population., Methods: We used an active appearance model-based approach to segment the preoperative CT of 21 osteoarthritic patients, which identified the osteophyte-free surfaces and estimated cartilage from the segmented bones; these geometries were used to construct patient-specific musculoskeletal models of the pre-diseased knee. Subsequently, implantations were simulated using the MA method, and a previously developed optimization technique was employed to find the optimal implant position that minimized the root mean square deviation between pre-diseased and postoperative ligament strains and kinematics., Results: There were evident biomechanical differences between the simulated patient models, but also trends that appeared reproducible at the population level. Optimizing the implant position significantly reduced the maximum observed strain root mean square deviations within the cohort from 36.5% to below 5.3% for all but the anterolateral ligament; and concomitantly reduced the kinematic deviations from 3.8 mm (SD 1.7) and 4.7° (SD 1.9°) with MA to 2.7 mm (SD 1.4) and 3.7° (SD 1.9°) relative to the pre-diseased state. To achieve this, the femoral component consistently required translational adjustments in the anterior, lateral, and proximal directions, while the tibial component required a more posterior slope and varus rotation in most cases., Conclusion: These findings confirm that MA-induced biomechanical alterations relative to the pre-diseased state can be reduced by optimizing the implant position, and may have implications to further advance pre-planning in robotic-assisted surgery in order to restore pre-diseased knee function., Competing Interests: This research was funded by Stryker European Operations Ltd., Ireland. P. Tzanetis, R. Fluit, and B. Koopman declare that they have no competing interests. K. de Souza is an employee of Stryker, and holds stock and stock options in Stryker Corporation. S. Robertson is also an employee of Stryker. N. Verdonschot is a consultant at Invibio Ltd. and Exactech., (© 2024 Tzanetis et al.)
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- 2024
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16. Efficacy and safety in early-phase clinical trials for refractory colorectal cancer: A meta-analysis.
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Smabers LP, Huismans MA, van Nieuwenhuijzen N, Minnema MC, Kranenburg O, Koopman M, Snippert HJG, May AM, and Roodhart JML
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- Humans, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Treatment Outcome, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology
- Abstract
Background: Despite recent metastatic colorectal cancer (mCRC) therapeutic innovations a comprehensive synthesis of patient outcome and risk-benefit assessment of phase 1/2 trials is missing. The aim of this meta-analysis is to assess efficacy, safety, and trends over time for phase 1 and 2 mCRC trials by examining clinical benefit rate (CBR), overall response rate (ORR), grade 3 or higher adverse events (AE), and discontinuation due to AE., Methods: The PRISMA guidelines were followed. We searched PubMed and Embase for publications of phase 1/2 trials between 2010-2021. Trials reporting on new therapies for treatment-refractory mCRC were included., Results: The search strategy yielded 4175 unique reports, of which 258 publications were eligible. These publications report data of 277 unique treatment arms. Overall ORR was 6 %, CBR was 27 % in phase 1 and 36 % in phase 2 trials. CBR increased from 23 % in 2010-2012 to 42 % in 2019-2021. Compared to 2010-2012, trials in 2019-2021 more often tested immunomodulators (4 % vs 23 %), included molecularly preselected populations (4 % vs 38 %) and younger patients (median age<60 44 % vs 66 %). Grade 3 + AE occurred in 35 % of patients, most frequently in trials investigating targeted treatments., Conclusions: Treatment efficacy in phase 1/2 trials is modest but improved from 2010 to 2021. This improvement is accompanied by a shift towards testing in a younger, fitter, and more strictly molecularly preselected population, as well as an increased focus on targeted and immunotherapies., Competing Interests: Declaration of Competing Interest The authors declare no known conflict of interests. The following interests may be considered as potential competing interests. J.M.L.R. grants/contracts: BMS, Pierre Fabre, Servier, Cleara Biotech, HUB organoids; Board Membership: Foundation Hubrecht Organoid Biobank. M.K. grants/contracts: Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, Roche, Sanofi, Personal Genome Diagnostics. M.C.M. grants/contracts: BeiGene; Consulting fees: Janssen-Cilag, GSK, CDR-life; Speakers bureaus: Janssen-Cilag, BMS, WebMD global. All grants were unrelated to the study and paid to individual’s institutions., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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17. Reply - Letter to editor entitled "Enhancing colorectal cancer survivorship: Integrating social work to optimize Dietary and lifestyle interventions".
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Wesselink E, Boshuizen HC, van Lanen AS, Kok DE, Derksen JWG, Smit KC, de Wilt JHW, Koopman M, May AM, Kampman E, and van Duijnhoven FJB
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Competing Interests: Conflict of interest All authors declare no conflicts of interest.
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- 2024
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18. Reply - Letter to the editor entitled "Oral health perspectives: The benefits of low-inflammatory diet and lifestyle".
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Wesselink E, Boshuizen HC, van Lanen AS, Kok DE, Derksen JWG, Smit KC, de Wilt JHW, Koopman M, May AM, Kampman E, and van Duijnhoven FJB
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- 2024
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19. Incision techniques for trigger thumb release: a comparison of outcomes of four types of skin incision.
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Koopman JE, Smit JM, Wouters RM, Selles RW, Michiel Zuidam J, and Hundepool CA
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- Humans, Female, Male, Middle Aged, Aged, Adult, Postoperative Complications, Retrospective Studies, Trigger Finger Disorder surgery, Patient Satisfaction
- Abstract
Although trigger thumb release is commonly performed, there is no consensus on the optimal skin incision. This study aimed to compare outcomes of four incision techniques, including V-shaped, oblique, transverse and longitudinal incisions. Outcomes included the Michigan Hand Outcomes Questionnaire, satisfaction with the treatment and postoperative complications. The results of 875 patients who underwent trigger thumb release were assessed. All groups demonstrated improvement in self-reported hand function (range of 10-14 points), pain (25-27 points) and aesthetics (4-7 points) from baseline to 3 months postoperatively with no differences between incision techniques. Of the patients, 76% reported good or excellent satisfaction with the outcome of treatment. Satisfaction and complication rates of the different incision techniques were similar. These findings imply that there is no clear benefit of one type of incision over another for trigger thumb release, suggesting that surgeons may use the technique of their preference. Level of evidence: III., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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20. Exploration of the relationship between general health-related problems and subclinical coronary artery disease: a cross-sectional study in a general population.
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Koopman MY, van der Ende MY, Reijnders JJW, Willemsen RTA, van Bruggen R, Gratama JWC, Kietselaer BLJH, van der Harst P, and Vliegenthart R
- Subjects
- Humans, Female, Male, Cross-Sectional Studies, Middle Aged, Netherlands epidemiology, Prospective Studies, Surveys and Questionnaires, Logistic Models, Health Status, Aged, Tomography, X-Ray Computed, Risk Factors, Health Behavior, Coronary Artery Disease epidemiology
- Abstract
Objective: To explore associations between general health-related problems and subclinical coronary artery disease (CAD), determined by CT coronary calcium score (CT-CCS), in a general population., Design: A cross-sectional design., Setting: This study was performed in a prospective population-based cohort, examining the health and health-related behaviour of individuals living in the Northern Netherlands., Participants: The initial cohort comprised 6763 participants ≥45 years of age who underwent CT-scanning. Participants were included for the current analysis if they filled in three validated questionnaires (Symptomatic Checklist-90, Research and Development Survey-36 and Reviving the Early Diagnosis of CardioVascular Diseases questionnaire (RED-CVD)) and did not have a history of cardiovascular disease. The final analysis included 6530 participants., Primary Outcome Measure: Backward-stepwise and forward-stepwise logistic regression analyses were performed to determine associations between general health-related problems and subclinical CAD (CCS≥100 and ≥300)., Results: The median age was 53 years (25th, 75th percentile: 48, 58); 57% were women. CRCS≥100 was found in 1236 (19%) participants, 437 (12%) in women and 799 (29%) men and CCS≥300 in 643 (9.9%) participants of which 180 (4.8%) were women and 463 (16.6%) men. In univariate analysis, in women the expectation of health to worsen (OR=1.13, 95% CI: 1.05 to 1.21), and in men reduced exercise intolerance (OR=1.14, 95% CI: 1.06 to 1.23) were associated with CCS≥100. The total RED-CVD score in women (OR=1.06, (95% CI: 1.05 to 1.08) and men (OR=1.07, 95% CI: 1.06 to 1.09), and in men also reduced exercise intolerance (OR=1.15, 95% CI: 1.06 to 1.25) and headache (OR=0.55, 95% CI: 0.38 to 0.79) were associated with CCS≥300. In multivariate analyses, only general health expectation in women was still significantly associated with subclinical CAD (CCS≥300) (OR=1.92, 95% CI: 1.56 to 2.37)., Conclusion: Only a few general health-related problems were associated with the presence of subclinical CAD in the general population, however, these problems showed no strong association. Therefore, using health-related symptoms does not seem useful to pre-select for CT-CCS., Trial Registration Number: CCMO Register, NL17981.042.07 and NL58592.042.16., Competing Interests: Competing interests: RV has received institutional research grants from Siemens Healthineers, and PvdH has received grant support by Siemens Healthineers and Guerbet. The other authors did not report any potential conflict of interest relevant to this article., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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21. Long-Term Risk of Subsequent Neoplasms in 5-Year Survivors of Childhood Neuroblastoma: A Dutch Childhood Cancer Survivor Study-LATER 3 Study.
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Westerveld ASR, Tytgat GAM, van Santen HM, van Noesel MM, Loonen J, de Vries ACH, Louwerens M, Koopman MMW, van der Heiden-van der Loo M, Janssens GO, de Krijger RR, Ronckers CM, van der Pal HJH, Kremer LCM, and Teepen JC
- Abstract
Purpose: Neuroblastoma survivors have an increased risk of developing subsequent malignant neoplasms (SMNs), but the risk of subsequent nonmalignant neoplasms (SNMNs) and risk factors are largely unknown. We analyzed the long-term risks and associated risk factors for developing SMNs and SNMNs in a well-characterized cohort of 5-year neuroblastoma survivors., Methods: We included 563 5-year neuroblastoma survivors from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort, diagnosed during 1963-2014. Subsequent neoplasms were ascertained by linkages with the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank (Palga) and medical chart review. We calculated standardized incidence ratios (SIRs), absolute excess risk (AER), and cumulative incidences. Multivariable competing risk regression analysis was used to evaluate risk factors., Results: In total, 23 survivors developed an SMN and 60 an SNMN. After a median follow-up of 23.7 (range, 5.0-56.3) years, the risk of SMN was elevated compared with the general population (SIR, 4.0; 95% CI, 2.5 to 5.9; AER per 10,000 person-years, 15.1). The 30-year cumulative incidence was 3.4% (95% CI, 1.9 to 6.0) for SMNs and 10.4% (95% CI, 7.3 to 14.8) for SNMNs. Six survivors developed an SMN after iodine-metaiodobenzylguanidine (
131I MIBG) treatment. Survivors treated with131I MIBG had a higher risk of developing SMNs (subdistribution hazard ratio [SHR], 5.7; 95% CI, 1.8 to 17.8) and SNMNs (SHR, 2.6; 95% CI, 1.2 to 5.6) compared with survivors treated without131I MIBG; results for SMNs were attenuated in high-risk patients only (SMNs SHR, 3.6; 95% CI, 0.9 to 15.3; SNMNs SHR, 1.5; 95% CI, 0.7 to 3.6)., Conclusion: Our results demonstrate that neuroblastoma survivors have an elevated risk of developing SMNs and a high risk of SNMNs.131I MIBG may be a treatment-related risk factor for the development of SMN and SNMN, which needs further validation. Our results emphasize the need for awareness of subsequent neoplasms and the importance of follow-up care.- Published
- 2024
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22. Facilitators and Barriers to Integrating Patient-Generated Blood Pressure Data into Primary Care EHR Workflows.
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Canfield SM and Koopman RJ
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- Humans, Patient Generated Health Data, Blood Pressure, Hypertension therapy, Electronic Health Records, Workflow, Primary Health Care
- Abstract
Background: Evidence supports using patient-generated blood pressure data for better outcomes in hypertension management. However, obstacles like dealing with home-generated paper data sets and questions of validity slowed the meaningful incorporation of home blood pressure into clinical care. As clinicians value patient data more, reliance on digital health solutions for data collection and shared decision-making grows., Objectives: The purpose of this study is to evaluate the design and early implementation of an electronic health record (EHR)-based data visualization tool and explore the barriers or facilitators to integrating) patients' home blood pressure data into the electronic workflow in the clinical setting. Findings can inform potential next steps for implementation and provide recommendations for leveraging patient-generated health data (PGHD) in hypertension management., Methods: We qualitatively explored pre- and early-implementation factors for integrating PGHD into clinicians' EHR interfaces intended to support shared decision-making using the Consolidated Framework for Implementation Research (CFIR). We collected data in the form of notes and transcripts from clinician focus groups, administrative leadership feedback sessions, research team observations, and recurring team meetings. This study took place at a midwestern academic health center., Results: We identify implementation facilitating factors, adoption considerations, and next steps across CFIR domains focusing on large-scale implementation. Key recommendations include aligning internal and external priorities, empowering champions to facilitate uptake, using intuitive design, and anticipating and planning for unintended consequences., Conclusion: These findings can guide future efforts to include PGHD in workflows, thus enhancing shared decision-making and laying the groundwork for larger implementations. Understanding the implementation barriers and facilitators to connect PGHD to clinician apps in the EHR workspace can promote their adoption and maintenance., Competing Interests: None declared., (Thieme. All rights reserved.)
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- 2024
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23. Imaging the immune sequelae of infection with SARS-CoV-2 in nonhuman primates by using two nanobody PET-tracers.
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Koopman G, Verhoeven T, Mooij P, Acar RF, Harmand T, Flanagan L, Bakker J, Böszörményi KP, Bontrop RE, Langermans JAM, Ploegh HL, Verschoor EJ, Vugts DJ, Pishesha N, and Stammes MA
- Subjects
- Animals, Lung immunology, Lung virology, Lung diagnostic imaging, Lung pathology, Disease Models, Animal, Antigen-Presenting Cells immunology, Humans, Macaca fascicularis, COVID-19 immunology, COVID-19 diagnostic imaging, Single-Domain Antibodies immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology, Positron-Emission Tomography
- Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa-DR expression profile, (2) virus-infected cells and viral particles using a nanobody against the SARS-CoV-2 spike protein. Two [
89 Zr]-labeled nanobodies that target the SARS-CoV-2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa-DR), respectively, are used to monitor their distribution during an experimental SARS-CoV-2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [89 Zr]anti-SARS-CoV-2 spike nanobody localized to SARS-CoV-2-associated lung lesions and the nasal mucosa, while the [89 Zr]anti-human leukocyte antigen (HLA)-DR nanobody was predominantly found in non-affected lung tissue after infection. We also detected, pi, upregulation of the Mafa-DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [89 Zr]-labeled nanobodies show recruitment of macrophages/monocytes in non-lesional lung tissue in cynomolgus macaques after experimental infection with SARS-CoV-2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)- Published
- 2024
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24. A regression-based approach to the CO 2 airborne fraction.
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Bennedsen M, Hillebrand E, and Koopman SJ
- Abstract
The global fraction of anthropogenically emitted carbon dioxide (CO
2 ) that stays in the atmosphere, the CO2 airborne fraction, has been fluctuating around a constant value over the period 1959 to 2022. The consensus estimate of the airborne fraction is around 44%. In this study, we show that the conventional estimator of the airborne fraction, based on a ratio of changes in atmospheric CO2 concentrations and CO2 emissions, suffers from a number of statistical deficiencies. We propose an alternative regression-based estimator of the airborne fraction that does not suffer from these deficiencies. Our empirical analysis leads to an estimate of the airborne fraction over 1959-2022 of 47.0% (± 1.1%; 1σ), implying a higher, and better constrained, estimate than the current consensus. Using climate model output, we show that a regression-based approach provides sensible estimates of the airborne fraction, also in future scenarios where emissions are at or near zero., (© 2024. The Author(s).)- Published
- 2024
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25. PBPK modeling of recombinant factor IX Fc fusion protein (rFIXFc) and rFIX to characterize the binding to type 4 collagen in the extravascular space.
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Cloesmeijer ME, Sjögren E, Koopman SF, Lenting PJ, Cnossen MH, and Mathôt RAA
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- Humans, Male, Models, Biological, Protein Binding, Half-Life, Collagen Type IV pharmacokinetics, Collagen Type IV metabolism, Collagen Type IV administration & dosage, Recombinant Fusion Proteins pharmacokinetics, Recombinant Fusion Proteins administration & dosage, Factor IX pharmacokinetics, Factor IX administration & dosage, Immunoglobulin Fc Fragments administration & dosage, Hemophilia B drug therapy, Hemophilia B metabolism
- Abstract
Patients with severe and sometimes moderate hemophilia B are prophylactically treated with factor IX concentrates to prevent bleeding. For some time now, various extended terminal half-life (EHL) recombinant factor IX concentrates are available allowing less frequent administration during prophylaxis in comparison to standard half-life recombinant FIX (rFIX). Especially, recombinant FIX-Fc fusion protein (rFIXFc; Alprolix®) exhibits a rapid distribution phase, potentially due to binding to type IV collagen (Col4) in the extravascular space. Studies suggest that the presence of extravascular rFIXFc is protective against bleeding as without measurable FIX activity in plasma, and no extra bleeding seems to occur. The physiologically based pharmacokinetic (PBPK) model for rFIXFc which we describe in this study, is able to accurately predict the observed concentration-time profiles of rFIXFc in plasma and is able to quantify the binding of rFIXFc to Col4 in the extravascular space after an intravenous dose of 50 IU/kg rFIXFc in a male population. Our model predicts that the total AUC of rFIXFc bound to Col4 in the extravascular space is approximately 19 times higher compared to the AUC of rFIXFc in plasma. This suggests that rFIXFc present in the extravascular compartment may play an important role in achieving hemostasis after rFIXFc administration. Further studies on extravascular distribution of rFIXFc and the distribution profile of other EHL-FIX concentrates are needed to evaluate the predictions of our PBPK model and to investigate its clinical relevance., (© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- 2024
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26. Use of automated assessment for determining associations of low muscle mass and muscle loss with overall survival in patients with colorectal cancer - A validation study.
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Smit KC, Derksen JWG, Kurk SA, Moeskops P, Koopman M, Veldhuis WB, and May AM
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- Humans, Female, Male, Middle Aged, Aged, Body Composition, Automation, Reproducibility of Results, Colorectal Neoplasms mortality, Muscle, Skeletal diagnostic imaging, Tomography, X-Ray Computed, Sarcopenia diagnostic imaging
- Abstract
Background: Low muscle mass and skeletal muscle mass (SMM) loss are associated with adverse patient outcomes, but the time-consuming nature of manual SMM quantification prohibits implementation of this metric in clinical practice. Therefore, we assessed the feasibility of automated SMM quantification compared to manual quantification. We evaluated both diagnostic accuracy for low muscle mass and associations of SMM (change) with survival in colorectal cancer (CRC) patients., Methods: Computed tomography (CT) images from CRC patients enrolled in two clinical studies were analyzed. We compared i) manual vs. automated segmentation of preselected slices at the third lumbar [L3] vertebra ("semi-automated"), and ii) manual L3-slice-selection + manual segmentation vs. automated L3-slice-selection + automated segmentation ("fully-automated"). Automated L3-selection and automated segmentation was performed with Quantib Body Composition v0.2.1. Bland-Altman analyses, within-subject coefficients of variation (WSCVs) and Intraclass Correlation Coefficients (ICCs) were used to evaluate the agreement between manual and automatic segmentation. Diagnostic accuracy for low muscle mass (defined by an established sarcopenia cut-off) was calculated with manual assessment as the "gold standard". Using either manual or automated assessment, Cox proportional hazard ratios (HRs) were used to study the association between changes in SMM (>5% decrease yes/no) during first-line metastatic CRC treatment and mortality adjusted for prognostic factors. SMM change was also assessed separately in weight-stable (<5%, i.e. occult SMM loss) patients., Results: In total, 1580 CT scans were analyzed, while a subset of 307 scans were analyzed in the fully-automated comparison. Included patients (n = 553) had a mean age of 63 ± 9 years and 39% were female. The semi-automated comparison revealed a bias of -2.41 cm
2 , 95% limits of agreement [-9.02 to 4.20], a WSCV of 2.25%, and an ICC of 0.99 (95% confidence intervals (CI) 0.97 to 1.00). The fully-automated comparison method revealed a bias of -0.08 cm2 [-10.91 to 10.75], a WSCV of 2.85% and an ICC of 0.98 (95% CI 0.98 to 0.99). Sensitivity and specificity for low muscle mass were 0.99 and 0.89 for the semi-automated comparison and 0.96 and 0.90 for the fully-automated comparison. SMM decrease was associated with shorter survival in both manual and automated assessment (n = 78/280, HR 1.36 [95% CI 1.03 to 1.80] and n = 89/280, HR 1.38 [95% CI 1.05 to 1.81]). Occult SMM loss was associated with shorter survival in manual assessment, but not significantly in automated assessment (n = 44/263, HR 1.43 [95% CI 1.01 to 2.03] and n = 51/2639, HR 1.23 [95% CI 0.87 to 1.74])., Conclusion: Deep-learning based assessment of SMM at L3 shows reliable performance, enabling the use of CT measures to guide clinical decision making. Implementation in clinical practice helps to identify patients with low muscle mass or (occult) SMM loss who may benefit from lifestyle interventions., Competing Interests: Declaration of competing interest MK reports institutional financial interests with Amgen, Bayer, BMS, Merck-Serono, Nordic Pharma, Roche, Servier, Sirtex, and Sanofi-Aventis. Miriam Koopman reports the following non-financial interests: an advisory role for ZON-MW, membership of the scientific board of the Dutch Cancer Society (KWF), chairmanship of the Dutch Colorectal Cancer Group (DCCG), and principal investigator (PI) of the Prospective Dutch Colorectal Cancer (PLCRC) cohort. WV was a co-founder of Quantib-U. PM was employed by Quantib-U. All other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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27. Perioperative transfusion study (PETS): Does a liberal transfusion protocol improve outcome in high-risk cardiovascular patients undergoing non-cardiac surgery? A randomised controlled pilot study.
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Ali S, Roubos S, Hoeks SE, Verbrugge SJC, Koopman-van Gemert AWMM, Stolker RJ, and van Lier F
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- Humans, Pilot Projects, Male, Female, Aged, Middle Aged, Myocardial Infarction blood, Myocardial Infarction therapy, Troponin T blood, Hemoglobins analysis, Hemoglobins metabolism, Perioperative Care methods, Vascular Surgical Procedures, Blood Transfusion
- Abstract
Background: Small studies have shown that patients with advanced coronary artery disease might benefit from a more liberal blood transfusion strategy. The goal of this pilot study was to test the feasibility of a blood transfusion intervention in a group of vascular surgery patients who have elevated cardiac troponins in rest., Methods: We conducted a single-centre, randomised controlled pilot study. Patients with a preoperative elevated high-sensitive troponin T undergoing non-cardiac vascular surgery were randomised between a liberal transfusion regime (haemoglobin >10.4 g/dL) and a restrictive transfusion regime (haemoglobin 8.0-9.6 g/dL) during the first 3 days after surgery. The primary outcome was defined as a composite endpoint of all-cause mortality, myocardial infarction or unscheduled coronary revascularization., Results: In total 499 patients were screened; 92 were included and 50 patients were randomised. Postoperative haemoglobin was different between the intervention and control group; 10.6 versus 9.8, 10.4 versus 9.4, 10.9 versus 9.4 g/dL on day one, two and three respectively (p < 0.05). The primary outcome occurred in four patients (16%) in the liberal transfusion group and in two patients (8%) in control group., Conclusion: This pilot study shows that the studied transfusion protocol was able to create a clinically significant difference in perioperative haemoglobin levels. Randomisation was possible in 10% of the screened patients. A large definitive trial should be possible to provide evidence whether a liberal transfusion strategy could decrease the incidence of postoperative myocardial infarction in high risk surgical patients., (© 2024 The Author(s). Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)
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- 2024
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28. Sleep Problems and Autism Impairments in a Large Community Sample of Children and Adolescents.
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Saletin JM, Koopman-Verhoeff ME, Han G, Barker DH, Carskadon MA, Anders TF, and Sheinkopf SJ
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- Humans, Female, Male, Child, Adolescent, Rhode Island epidemiology, Autism Spectrum Disorder complications, Sleep Wake Disorders epidemiology
- Abstract
Sleep problems are common in individuals with autism spectrum disorder (ASD). How sleep problems reflect specific ASD phenotypes is unclear. We studied whether sleep problems indexed functional impairment in a heterogeneous community sample of individuals with ASD. We analyzed 977 probands (233 females; age = 11.27 ± 4.13 years) from the Rhode Island Consortium for Autism Research and Treatment dataset, a unique public-private-academic collaboration involving all major points of service for families in Rhode Island. We found that individuals with a confirmed diagnosis of ASD were more likely to have sleep problems. However, across the whole sample and above and beyond a formal diagnosis, sleep problems were dimensionally associated with worse social impairment and poorer adaptive functioning. By using a large dataset reflective of the diversity of presentations in the community, this study underscores the importance of considering sleep problems in clinical practice to improve adaptive functioning in individuals with ASD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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29. Validity of Cardiopulmonary Exercise Testing for Assessing Aerobic Capacity in Neuromuscular Diseases.
- Author
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Veneman T, Koopman FS, Oorschot S, de Koning JJ, Bongers BC, Nollet F, and Voorn EL
- Subjects
- Humans, Male, Middle Aged, Female, Aged, Adult, Muscle Strength physiology, Exercise Tolerance physiology, Postpoliomyelitis Syndrome physiopathology, Postpoliomyelitis Syndrome rehabilitation, Reproducibility of Results, Charcot-Marie-Tooth Disease physiopathology, Pulmonary Gas Exchange physiology, Exercise Test methods, Oxygen Consumption physiology, Heart Rate physiology, Neuromuscular Diseases physiopathology, Neuromuscular Diseases rehabilitation
- Abstract
Objectives: To determine the content validity of cardiopulmonary exercise testing (CPET) for assessing peak oxygen uptake (VO
2peak ) in neuromuscular diseases (NMD)., Design: Baseline assessment of a randomized controlled trial., Setting: Academic hospital., Participants: Eighty-six adults (age: 58.0±13.9 y) with Charcot-Marie-Tooth disease (n=35), postpolio syndrome (n=26), or other NMD (n=25)., Intervention: Not applicable., Main Outcome Measures: Workload, gas exchange variables, heart rate, and ratings of perceived exertion were measured during CPET on a cycle ergometer, supervised by an experienced trained assessor. Muscle strength of the knee extensors was assessed isometrically with a fixed dynamometer. Criteria for confirming maximal cardiorespiratory effort during CPET were established during 3 consensus meetings of an expert group. The percentage of participants meeting these criteria was assessed to quantify content validity., Results: The following criteria were established for maximal cardiorespiratory effort: a plateau in oxygen uptake (VO2plateau ) as the primary criterion, or 2 of 3 secondary criteria: (1) peak respiratory exchange ratio (RERpeak ) ≥1.10 (2), peak heart rate ≥85% of predicted maximal heart rate; and (3) peak rating of perceived exertion (RPEpeak ) ≥17 on the 6-20 Borg scale. These criteria were attained by 71 participants (83%). VO2plateau , RERpeak ≥1.10, peak heart rate ≥85%, and RPEpeak ≥17 were attained by 31%, 73%, 69%, and 72% of the participants, respectively. Peak workload, VO2peak , and knee extension muscle strength were significantly higher, and body mass index was lower (all P<.05), in participants with maximal cardiorespiratory effort than other participants., Conclusions: Most people with NMD achieved maximal cardiorespiratory effort during CPET. This study provides high quality evidence of sufficient content validity of VO2peak as a maximal aerobic capacity measure. Content validity may be lower in more severely affected people with lower physical fitness., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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30. Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer.
- Author
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van de Weerd S, Torang A, van den Berg I, Lammers V, van den Bergh S, Brouwer N, Nagtegaal ID, Koopman M, Vink GR, van der Baan FH, van Krieken H, Koster J, Ijzermans JN, Roodhart JML, and Medema JP
- Subjects
- Humans, Chemotherapy, Adjuvant methods, Female, Male, Aged, Middle Aged, Prognosis, Biomarkers, Tumor genetics, Disease-Free Survival, Aged, 80 and over, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colonic Neoplasms drug therapy, Colonic Neoplasms mortality, Colonic Neoplasms pathology, Colonic Neoplasms genetics, Colonic Neoplasms classification, Neoplasm Staging, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology
- Abstract
The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p = .03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p = .01, HR 0.27; p < .01, HR 0.19; p < .01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p = .51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2025
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31. Generating synthetic clinical text with local large language models to identify misdiagnosed limb fractures in radiology reports.
- Author
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Liu J, Koopman B, Brown NJ, Chu K, and Nguyen A
- Subjects
- Humans, Diagnostic Errors, Artificial Intelligence, Electronic Health Records, Fractures, Bone diagnostic imaging, Natural Language Processing
- Abstract
Large language models (LLMs) demonstrate impressive capabilities in generating human-like content and have much potential to improve the performance and efficiency of healthcare. An important application of LLMs is to generate synthetic clinical reports that could alleviate the burden of annotating and collecting real-world data in training AI models. Meanwhile, there could be concerns and limitations in using commercial LLMs to handle sensitive clinical data. In this study, we examined the use of open-source LLMs as an alternative to generate synthetic radiology reports to supplement real-world annotated data. We found LLMs hosted locally can achieve similar performance compared to ChatGPT and GPT-4 in augmenting training data for the downstream report classification task of identifying misdiagnosed fractures. We also examined the predictive value of using synthetic reports alone for training downstream models, where our best setting achieved more than 90 % of the performance using real-world data. Overall, our findings show that open-source, local LLMs can be a favourable option for creating synthetic clinical reports for downstream tasks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2025
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32. Mitochondrial Morphofunctional Profiling in Primary Human Skin Fibroblasts Using TMRM and Mitotracker Green Co-staining.
- Author
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Bergmans JMM, van de Westerlo EMA, Grefte S, Adjobo-Hermans MJW, and Koopman WJH
- Subjects
- Humans, Membrane Potential, Mitochondrial, Cells, Cultured, Staining and Labeling methods, Fluorescent Dyes chemistry, Fibroblasts metabolism, Fibroblasts cytology, Mitochondria metabolism, Rhodamines chemistry, Skin cytology, Skin metabolism, Microscopy, Fluorescence methods
- Abstract
Mitochondrial morphology and membrane potential (Δψ) are important readouts of mitochondrial function. Integrated analysis of these parameters in living cells can be performed using fluorescent lipophilic cations, which enter cells and accumulate in the mitochondrial matrix in a Δψ-dependent manner. Here, we describe the use of tetramethylrhodamine methyl ester (TMRM) and Mitotracker Green FM (MG) for mitochondrial morphology and semiquantitative Δψ analysis in living primary human skin fibroblasts (PHSFs). Practically, we present an integrated protocol to quantify mitochondrial morphology parameters and signal intensity using epifluorescence microscopy of PHSFs co-stained with TMRM and MG. This approach performs best using large flat cells like PHSFs, which display a high mitochondria-specific fluorescence signal and are imaged at a relatively high (x40) magnification., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2025
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33. Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA).
- Author
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Wydrych A, Pakuła B, Jakubek-Olszewska P, Janikiewicz J, Dobosz AM, Cudna A, Rydzewski M, Pierzynowska K, Gaffke L, Cyske Z, Rintz E, Kurkowska-Jastrzębska I, Cwyl M, Pinton P, Węgrzyn G, Koopman WJH, Dobrzyń A, Skowrońska M, Lebiedzińska-Arciszewska M, and Wieckowski MR
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Brain metabolism, Brain pathology, Iron Metabolism Disorders genetics, Iron Metabolism Disorders metabolism, Iron Metabolism Disorders pathology, Neuroaxonal Dystrophies metabolism, Neuroaxonal Dystrophies genetics, Neuroaxonal Dystrophies pathology, Oxidative Phosphorylation, Pantothenate Kinase-Associated Neurodegeneration genetics, Pantothenate Kinase-Associated Neurodegeneration pathology, Pantothenate Kinase-Associated Neurodegeneration metabolism, Fibroblasts metabolism, Fibroblasts pathology, Iron metabolism, Mitochondrial Proteins metabolism, Mitochondrial Proteins genetics, Mutation
- Abstract
Mutations in the following genes: PANK2, PLA2G6, C19orf12, WDR45, CP, FA2H, ATP13A2, FTL, DCAF17, and CoASY are associated with the development of different subtypes of inherited rare disease Neurodegeneration with Brain Iron Accumulation (NBIA). Additionally, recently described mutations in FTH1, AP4M1, REPS1, SCP2, CRAT and GTPBP2 affecting iron and lipid metabolism also are thought to be involved in NBIA development. Four main subtypes, pantothenate kinase-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), mitochondrial membrane protein-associated neurodegeneration (MPAN) and beta-propeller protein-associated neurodegeneration (BPAN), are responsible for up to 82 % of all NBIA cases. Here we studied fibroblasts from 11 patients with pathogenic mutations in C19orf12, and demonstrate various cellular aberrations. Differences between fibroblasts from healthy individuals and MPAN patients were potentiated when cells were grown under oxidative phosphorylation (OXPHOS) promoting condition suggesting an impaired metabolic flexibility. The extent of some of the cellular aberrations quantitatively correlated with disease severity, suggesting their involvement in the NBIA pathomechanism., Competing Interests: Declaration of competing interest, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2025
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34. Ndufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response.
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van de Wal MAE, Doornbos C, Bibbe JM, Homberg JR, van Karnebeek C, Huynen MA, Keijer J, van Schothorst EM, 't Hoen PAC, Janssen MCH, Adjobo-Hermans MJW, Wieckowski MR, and Koopman WJH
- Subjects
- Animals, Mice, Oxidative Phosphorylation, Disease Models, Animal, Proteome metabolism, Proteome genetics, Mitochondrial Diseases, Electron Transport Complex I metabolism, Electron Transport Complex I genetics, Electron Transport Complex I deficiency, Mice, Knockout, Leigh Disease genetics, Leigh Disease metabolism, Brain metabolism
- Abstract
Paediatric Leigh syndrome (LS) is an early-onset and fatal neurodegenerative disorder lacking treatment options. LS is frequently caused by mutations in the NDUFS4 gene, encoding an accessory subunit of mitochondrial complex I (CI), the first complex of the oxidative phosphorylation (OXPHOS) system. Whole-body Ndufs4 knockout (KO) mice (WB-KO mice) are widely used to study isolated CI deficiency, LS pathology and interventions. These animals develop a brain-specific phenotype via an incompletely understood pathomechanism. Here we performed a quantitative analysis of the sub-brain proteome in six-weeks old WB-KO mice vs. wildtype (WT) mice. Brain regions comprised of a brain slice (BrSl), cerebellum (CB), cerebral cortex (CC), hippocampus (HC), inferior colliculus (IC), and superior colliculus (SC). Proteome analysis demonstrated similarities between CC/HC, and between IC/SC, whereas BrSl and CB differed from these two groups and each other. All brain regions displayed greatly reduced levels of two CI structural subunits (NDUFS4, NDUFA12) and an increased level of the CI assembly factor NDUFAF2. The level of CI-Q module subunits was significantly more reduced in IC/SC than in BrSl/CB/CC/HC, whereas other OXPHOS complex levels were not reduced. Gene ontology and pathway analysis demonstrated specific and common proteome changes between brain regions. Across brain regions, upregulation of cold-shock-associated proteins, mitochondrial fatty acid (FA) oxidation and synthesis (mtFAS) were the most prominent. FA-related pathways were predominantly upregulated in CB and HC. Based upon these results, we argue that stimulation of these pathways is futile and pro-pathological and discuss alternative strategies for therapeutic intervention in LS. SIGNIFICANCE: The Ndufs4 knockout mouse model is currently the most relevant and most widely used animal model to study the brain-linked pathophysiology of human Leigh Syndrome (LS) and intervention strategies. We demonstrate that the Ndufs4 knockout brain engages futile and pro-pathological responses. These responses explain both negative and positive outcomes of intervention studies in Leigh Syndrome mice and patients, thereby guiding novel intervention opportunities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2025
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35. The user-centered design and development of a childhood and adolescent obesity Electronic Health Record tool, a mixed-methods study.
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Bosworth KT, Ghosh P, Flowers L, Proffitt R, Koopman RJ, Tosh AK, Wilson G, and Braddock AS
- Abstract
Background: Childhood and adolescent obesity are persistent public health issues in the United States. Childhood obesity Electronic Health Record (EHR) tools strengthen provider-patient relationships and improve outcomes, but there are currently limited EHR tools that are linked to adolescent mHealth apps. This study is part of a larger study entitled, CommitFit, which features both an adolescent-targeted mobile health application (mHealth app) and an ambulatory EHR tool. The CommitFit mHealth app was designed to be paired with the CommitFit EHR tool for integration into clinical spaces for shared decision-making with patients and clinicians., Objectives: The objective of this sub-study was to identify the functional and design needs and preferences of healthcare clinicians and professionals for the development of the CommitFit EHR tool, specifically as it relates to childhood and adolescent obesity management., Methods: We utilized a user-centered design process with a mixed-method approach. Focus groups were used to assess current in-clinic practices, deficits, and general beliefs and preferences regarding the management of childhood and adolescent obesity. A pre- and post-focus group survey helped assess the perception of the design and functionality of the CommitFit EHR tool and other obesity clinic needs. Iterative design development of the CommitFit EHR tool occurred throughout the process., Results: A total of 12 healthcare providers participated throughout the three focus group sessions. Two themes emerged regarding EHR design: (1) Functional Needs, including Enhancing Clinical Practices and Workflow, and (2) Visualization, including Colors and Graphs. Responses from the surveys ( n = 52) further reflect the need for Functionality and User-Interface Design by clinicians. Clinicians want the CommitFit EHR tool to enhance in-clinic adolescent lifestyle counseling, be easy to use, and presentable to adolescent patients and their caregivers. Additionally, we found that clinicians preferred colors and graphs that improved readability and usability. During each step of feedback from focus group sessions and the survey, the design of the CommitFit EHR tool was updated and co-developed by clinicians in an iterative user-centered design process., Conclusion: More research is needed to explore clinician actual user analytics for the CommitFit EHR tool to evaluate real-time workflow, design, and function needs. The effectiveness of the CommitFit mHealth and EHR tool as a weight management intervention needs to be evaluated in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bosworth, Ghosh, Flowers, Proffitt, Koopman, Tosh, Wilson and Braddock.)
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- 2024
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36. A Peptide Strategy for Inhibiting Different Protein Aggregation Pathways.
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Garfagnini T, Ferrari L, Koopman MB, Dekker FA, Halters S, Van Kappel E, Mayer G, Bressler S, Maurice MM, Rüdiger SGD, and Friedler A
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- Humans, Hydrophobic and Hydrophilic Interactions, tau Proteins metabolism, tau Proteins chemistry, Amyloid chemistry, Amyloid metabolism, Amyloid antagonists & inhibitors, Huntingtin Protein chemistry, Huntingtin Protein metabolism, Axin Protein chemistry, Axin Protein metabolism, Protein Aggregation, Pathological metabolism, Protein Aggregation, Pathological drug therapy, Alzheimer Disease metabolism, Alzheimer Disease drug therapy, Amino Acid Sequence, Peptides chemistry, Peptides pharmacology, Protein Aggregates drug effects
- Abstract
Protein aggregation correlates with many human diseases. Protein aggregates differ in structure and shape. Strategies to develop effective aggregation inhibitors that reach the clinic failed so far. Here, we developed a family of peptides targeting early aggregation stages for both amorphous and fibrillar aggregates of proteins unrelated in sequence and structure. They act on dynamic precursors before mechanistic differentiation takes place. Using peptide arrays, we first identified peptides inhibiting the amorphous aggregation of a molten globular, aggregation-prone mutant of the Axin tumor suppressor. Optimization revealed that the peptides activity did not depend on their sequences but rather on their molecular determinants: a composition of 20-30 % flexible, 30-40 % aliphatic and 20-30 % aromatic residues, a hydrophobicity/hydrophilicity ratio close to 1, and an even distribution of residues of different nature throughout the sequence. The peptides also suppressed fibrillation of Tau, a disordered protein that forms amyloids in Alzheimer's disease, and slowed down that of Huntingtin Exon1, an amyloidogenic protein in Huntington's disease, both entirely unrelated to Axin. Our compounds thus target early stages of different aggregation mechanisms, inhibiting both amorphous and amyloid aggregation. Such cross-mechanistic, multi-targeting aggregation inhibitors may be lead compounds for developing drug candidates against various protein aggregation diseases., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
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- 2024
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37. Effectiveness of an mHealth App That Uses Financial Incentives and Gamification to Promote Health Behavior Change in Adolescents and Caregivers: Protocol for a Clinic-Based Randomized Controlled Trial.
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Braddock A, Ghosh P, Montgomery E, Lim C, Ghosh J, Henry N, Popescu M, Kimchi K, Guo C, Bosworth KT, and Koopman RJ
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- Humans, Adolescent, Male, Female, Health Promotion methods, Video Games, Adult, Mobile Applications, Health Behavior, Motivation, Telemedicine, Caregivers psychology
- Abstract
Background: Adolescent and adult obesity continues to be a public health epidemic in the United States. Despite the popularity of mHealth apps with gamification among adolescents, there are insufficient studies to evaluate the efficacy of gamified mHealth apps and financial incentives to motivate sustained health behavior change in adolescents or their adult caregivers., Objective: This study aims to evaluate the effectiveness of gamification techniques and financial incentives used in the novel "CommitFit" mHealth app to motivate health behavior change and improve various mental and physical health metrics in adolescents and their caregivers., Methods: This study is a 3-month randomized controlled trial (RCT) with 30 adolescents (aged 13-15 years) and their adult caregivers (N=60). It evaluates "CommitFit," which uses gamification including points and leaderboards to motivate logging and achievement of self-selected health behavior goals (eg, more water, sleep, physical activity, fruits, or vegetables or fewer sugary beverages). The RCT had three arms, each with 10 dyads: (1) CommitFit-only users; (2) CommitFit$, where adolescents were paid US $0.05 for each point they earned; and (3) waitlist control. Intervention dyads used the app for 3 months and had the option to use it for the fourth month without prompts or extra financial incentives. User analytic software was used to evaluate the frequency of user logs and goal achievement. Monthly surveys evaluated self-reported change in the 5 CommitFit health behaviors. Changes in BMI and blood pressure were evaluated for all participants at 3 clinical visits. Mental health, gamification, and behavior economics surveys were completed during the clinical visits., Results: Recruitment began in August 2023 and was completed in 10 weeks. The research team successfully recruited and enrolled 30 dyads. Researchers emailed and called 89 caregivers on a physician-approved adolescent patient list, a 33% recruitment rate. Data collection and analysis will be conducted in the spring and summer of 2024. The results of this study are anticipated to be published between late 2024 and early 2025., Conclusions: This RCT will expand knowledge of the effectiveness of gamification techniques, financial incentives, and mHealth apps to motivate sustained health behavior change among adolescents and caregivers. These results may offer new opportunities to caregivers, health insurers, health care systems, and clinicians to motivate health behavior change in adolescents and caregivers, with the ultimate goal of preventing or reducing obesity and obesity-related diseases. Additional gamification, mental health surveys, and app user analytics included in the study may provide further insight into the characteristics of adolescents or caregivers who would benefit the most from using a gamified mHealth app like CommitFit., International Registered Report Identifier (irrid): DERR1-10.2196/63505., (©Amy Braddock, Parijat Ghosh, Emma Montgomery, Crystal Lim, Jaya Ghosh, Nicole Henry, Mihail Popescu, Kimberly Kimchi, Congyu Guo, K Taylor Bosworth, Richelle J Koopman. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.09.2024.)
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- 2024
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38. Kinetics and Retention of Polystyrenesulfonate for Proteoglycan Replacement in Cartilage.
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Sundar S, Koopman A, Manzoni TJ, Xie W, Bhatti QU, Lo CY, Damani VS, Yang AN, Pochan D, Parreno J, Engiles JB, Kayser LV, and Dhong C
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- Animals, Cattle, Kinetics, Osteoarthritis drug therapy, Osteoarthritis pathology, Glycosaminoglycans chemistry, Chondroitin Sulfates chemistry, Cartilage, Articular, Polystyrenes chemistry, Proteoglycans chemistry
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Tissue hydration provides articular cartilage with dynamic viscoelastic properties. Early stage osteoarthritis (OA) is marked by loss of proteoglycans and glycosaminoglycans (GAG), lowering fixed charge density, and impairing tissue osmotic function. The most common GAG replacement, chondroitin sulfate (CS), has failed to show effectiveness. Here, we investigated a synthetic polyelectrolyte, poly(styrenesulfonate) (PSS), both as a model compound to investigate polyelectrolyte transport in cartilage, and as a potential candidate to restore bulk fixed charge density in cartilage with GAG loss. Through bovine explants and histology, we determined zonal-based effective diffusion coefficients for three different molecular weights of PSS. Compared to CS, PSS was retained longer in GAG-depleted cartilage in static and compression-based desorption experiments. We explained enhanced solute performance of PSS by its more compact morphology and higher charge density by small-angle X-ray scattering. This study may improve design of GAG mimetic molecules for repairing osmotic function in OA cartilage.
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- 2024
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39. Investigating the Ordering Structure of Clustered Items Using Nonparametric Item Response Theory.
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Koopman L and Braeken J
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Educational and psychological tests with an ordered item structure enable efficient test administration procedures and allow for intuitive score interpretation and monitoring. The effectiveness of the measurement instrument relies to a large extent on the validated strength of its ordering structure. We define three increasingly strict types of ordering for the ordering structure of a measurement instrument with clustered items: a weak and a strong invariant cluster ordering and a clustered invariant item ordering. Following a nonparametric item response theory (IRT) approach, we proposed a procedure to evaluate the ordering structure of a clustered item set along this three-fold continuum of order invariance. The basis of the procedure is (a) the local assessment of pairwise conditional expectations at both cluster and item level and (b) the global assessment of the number of Guttman errors through new generalizations of the H -coefficient for this item-cluster context. The procedure, readily implemented in R, is illustrated and applied to an empirical example. Suggestions for test practice, further methodological developments, and future research are discussed., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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40. A national study of firearm exposure and safety training among rural youth.
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Koopman JL, Linden BM, Sinik MR, Wetjen KM, Hoogerwerf PJ, Liao J, and Jennissen CA
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Background: Data regarding rural youths' experience with firearms, including safety training, is highly limited despite their frequent presence in homes. Our objective was to investigate rural adolescents' use of firearms and whether they had received formal firearm training., Methods: A convenience sample of 2021 National FFA (formerly Future Farmers of America) Convention & Expo attendees were given an anonymous survey at the University of Iowa Stead Family Children's Hospital injury prevention booth. The survey explored their use of rifles/shotguns and handguns and whether they had completed a certified firearm safety course. Descriptive and comparative analyses, including multivariable logistic regression analyses, were performed on compiled data., Results: 3206 adolescents ages 13-18 years participated with 45% reporting they lived on a farm or ranch. The vast majority of participants (85%) had fired a rifle/shotgun; 43% reported firing them > 100 times. Of those that had fired rifles/shotguns, 41% had done so before 9 years old. Most had also fired a handgun (69%), with 23% having fired handguns > 100 times. Of those that had fired handguns, 44% had done so before 11 years. Average age for first firing rifles/shotguns was 9.5 (SD 3.1) years, and 11.1 (SD 3.0) years for handguns. Males, non-Hispanic Whites, and those living on farms or in the country had significantly greater percentages who had fired a rifle/shotgun or a handgun. Significant differences were also seen by U.S. census region. Over half (64%) reported having gone hunting. Of those that had used a firearm, 67% had completed a firearm safety training course. Overall, 23% were/had been members of a school or club shooting team and of these, 87% had taken a safety course., Conclusions: Most FFA member participants had fired both rifles/shotguns and handguns, many at very young ages. Significant differences in firearm use were noted by demographic factors including the home setting (i.e., farms and ranches) and their U.S. census region. Nearly one-third of adolescent firearm users had not received formal safety training. Promoting firearm safety should include advising families on when it is developmentally appropriate to introduce youth to firearms and on the importance of firearm safety training., (© 2024. The Author(s).)
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- 2024
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41. Amyloid PET disclosure in subjective cognitive decline: Patient experiences over time.
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Hendriksen HMA, de Rijke TJ, Fruijtier A, van de Giessen E, van Harten AC, van Leeuwenstijn-Koopman MSSA, van der Schaar J, Trieu C, Visser D, Smets EMA, Visser LNC, and van der Flier WM
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- Humans, Female, Male, Aged, Surveys and Questionnaires, Disclosure, Middle Aged, Amyloid metabolism, Positron-Emission Tomography, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction psychology
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Introduction: We disclosed amyloid positron emission tomography (PET) results in individuals with subjective cognitive decline (SCD) and studied patient experiences and outcomes over a 6-month period., Methods: Fifty-seven participants from the Subjective Cognitive Impairment Cohort (SCIENCe) (66 ± 8 years, 21 [37%] F, Mini-Mental State Examination 29 ± 1, 15 [26%] amyloid positive [A+]) completed questionnaires 1 week prior (T0), 1 day after (T1), and 6 months after amyloid PET disclosure (T2). Questionnaires addressed patient-reported experiences and outcomes., Results: Independent of amyloid status, participants were satisfied with the consultation (scale 1-10; 7.9 ± 1.7) and information provided (scale 1-4; T1: 3.3 ± 0.9, T2: 3.2 ± 0.8). After 6 months, A+ participants reported more information needs (45% vs. 12%, p = 0.02). Independent of amyloid status, decision regret (scale 1-5; A+: 1.5 ± 0.9, A-: 1.4 ± 0.6, p = 0.53) and negative emotions (negative affect, uncertainty, anxiety) were low (all p > 0.15 and P
interaction > 0.60)., Discussion: Participants with SCD valued amyloid PET disclosure positively, regardless of amyloid status. The need for information after 6 months, which was stronger in A+ individuals, underscores the importance of follow-up., Highlights: Participants with subjective cognitive decline (SCD) positively valued amyloid positron emission tomography (PET) disclosure. Participants with SCD experienced low levels of decision regret. We did not observe an increase in negative emotions. After 6 months, amyloid-positive individuals wanted more information., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)- Published
- 2024
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42. Survival and patient-reported outcomes of real-world high-risk stage II and stage III colon cancer patients after reduction of adjuvant CAPOX duration from 6 to 3 months.
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Franken IA, van der Baan FH, Vink GR, May AM, van Grevenstein WMU, Koopman M, and Roodhart JML
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- Humans, Male, Female, Chemotherapy, Adjuvant, Aged, Middle Aged, Netherlands, Oxaliplatin therapeutic use, Oxaliplatin administration & dosage, Capecitabine administration & dosage, Capecitabine therapeutic use, Time Factors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aged, 80 and over, Registries, Colonic Neoplasms mortality, Colonic Neoplasms pathology, Colonic Neoplasms drug therapy, Patient Reported Outcome Measures, Neoplasm Staging
- Abstract
Aim: Adjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs)., Methods: Patients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015-2016) versus after (2018-2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs., Results: Patients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89-1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89-1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66-1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3-31.1] to 16.5 [14.4-18.6]) and better quality of life (n = 396; 80.9 [78.6-83.2] to 83.9 [82.8-84.9]), but no significant difference in workability (n = 120; 31.5 [27.9-35.1]) to 35.3 [33.8-36.7]), with reduction from 6 to 3 months of CAPOX., Conclusion: This real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: I.A.F: Grant to institution: DoMore Diagnostics. F.H.B: Payment to institution from Personal Genome Diagnostics. G.R.V: Grants to institution and/or nonfinancial support: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly, Delfi Diagnostics, Nordic all financial supports transferred to the institute. A.M.M and W.M.U.G: declare no potential conflicts of interests. M.K: advisory role: Eisai, Nordic Farma, Merck-Serono, Pierre Fabre, Servier. Institutional scientific grants: Bayer, Bristol Myers Squibb, Merck, Personal Genome Diagnostics (PGDx), Pierre Fabre, Roche, Sirtex, Servier. Non-financial interests: chair of the ESMO RWD-DH working group, co- chair: DCCG, PI PLCRC (national observational cohort study), involved in several clinical trials as PI or co-investigator in CRC. J.M.L.R: institutional financial interests: Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, Cleara Biotech., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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43. Dietary and lifestyle inflammation scores in relation to colorectal cancer recurrence and all-cause mortality: A longitudinal analysis.
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Wesselink E, Boshuizen HC, van Lanen AS, Kok DE, Derksen JWG, Smit KC, de Wilt JHW, Koopman M, May AM, Kampman E, and van Duijnhoven FJB
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- Humans, Male, Female, Middle Aged, Longitudinal Studies, Prospective Studies, Aged, Risk Factors, Proportional Hazards Models, Colorectal Neoplasms mortality, Inflammation mortality, Neoplasm Recurrence, Local mortality, Life Style, Diet statistics & numerical data
- Abstract
Aim: The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality., Methods: Data of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis. The dietary and lifestyle inflammation scores (DIS and LIS) were used to evaluate the inflammatory potential of diet and lifestyle. Joint modelling, combining mixed models and Cox proportional hazards regression, were used to assess associations between DIS and LIS over time and CRC recurrence and all-cause mortality. Interactions between DIS and LIS were assessed using time-dependent Cox proportional hazard regression., Results: The median follow-up time was 4.8 (IQR 2.9-6.9) years for recurrence and 5.7 (IQR 3.5-8.5) years for all-cause mortality, with 363 and 453 events, respectively. A higher DIS as well as LIS was associated with a higher risk of all-cause mortality (HR
DIScontinuous 1.09 95%CI 1.02; 1.15; HRLIScontinuous 1.24 95%CI 1.05; 1.46). Individuals who were in the upper tertile of both DIS and LIS had the highest all-cause mortality risk (HR 1.62 95%CI 1.16; 2.28), compared to the individuals in the lowest tertile of both DIS and LIS. No consistent associations with recurrence were observed., Conclusion: A more pro-inflammatory diet and lifestyle was associated with a higher risk of all-cause mortality, but not recurrence, in CRC survivors., Competing Interests: Conflict of interest The authors declare no conflicts of interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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44. Satisfaction of Paediatric Oncology Patients, Survivors, and Nurses with the Position of Their Totally Implantable Venous Access Port (SPACE-Study).
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van den Bosch CH, van de Ven CP, Hulsker CCC, Bökkerink GMJ, Terwisscha-van Scheltinga CEJ, van de Wetering MD, Koopman MMW, van der Pal HJH, Wijnen MWHA, and van der Steeg AFW
- Subjects
- Humans, Cross-Sectional Studies, Female, Child, Male, Adolescent, Catheterization, Central Venous methods, Cicatrix etiology, Young Adult, Cancer Survivors psychology, Catheters, Indwelling, Adult, Netherlands, Vascular Access Devices, Caregivers psychology, Patient Satisfaction, Neoplasms
- Abstract
Background: To compare paediatric oncologic vascular access ports located on the anterior thoracic wall to ports on the lower lateral thoracic wall, in terms of perceived port-related hindrance and scar-quality., Methods: A cross-sectional survey study including paediatric oncology patients (≥8-<19 yrs), caregivers (in patients <8 yrs), survivors (>22 yrs with only anterior ports) and nurses of the Princess Máxima Center, the Netherlands, was performed. The survey consisted of questions regarding satisfaction, hindrance during daily life, and port position preference. For survivors, scar-quality was assessed using the validated Patient and Observer Scar Assessment Scale (POSAS 2.0); a high score (i.e., a displeasing scar) was defined as a score higher than the third quartile of the median for that question., Results: In total, 147 participants were included; 83 patients/caregivers, 31 survivors, and 33 nurses. Overall, 81 % was satisfied with the position of their port. Satisfaction, hindrance and complications did not differ between anterior and lower lateral ports. For the anterior position, minimal pressure on the port during daily life was a mentioned reason to prefer this position. For the lower lateral position, less visibility of the scar and easiest access were mentioned. Of all survivors with an anterior port scar, one in five had a displeasing scar and all scars observed were widened. Female patients preferred a lower lateral port, and scar-quality was better for left-sided port scars., Conclusion: The port position should be chosen together with patients/caregivers based on the (dis-)advantages of each position, as identified by this study., Level of Evidence: II., Competing Interests: Conflicts of interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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45. Associations between low- and high-fat dairy intake and recurrence risk in people with stage I-III colorectal cancer differ by sex and primary tumour location.
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van Lanen AS, Kok DE, Wesselink E, Derksen JWG, May AM, Smit KC, Koopman M, de Wilt J, Kampman E, and van Duijnhoven FJB
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- Humans, Male, Female, Middle Aged, Aged, Prospective Studies, Dietary Fats administration & dosage, Dietary Fats adverse effects, Sex Factors, Risk Factors, Proportional Hazards Models, Diet, High-Fat adverse effects, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local epidemiology, Dairy Products, Colorectal Neoplasms pathology, Colorectal Neoplasms epidemiology, Neoplasm Staging
- Abstract
We previously demonstrated that intake of low-fat dairy, but not high-fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I-III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low- and high-fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow-up of 5.0 years, 331 recurrences were detected. A higher intake of low-fat dairy was associated with a reduced risk of recurrence (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34-0.77) than in women (HR: 0.84, 95% CI: 0.47-1.49). A higher intake of high-fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03-2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54-1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low-fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high-fat dairy intake may be specifically important in people with colon cancer., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2024
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46. Trastuzumab deruxtecan in HER2-positive metastatic colorectal cancer: less is more?
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Roodhart JML and Koopman M
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- Humans, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Immunoconjugates administration & dosage, Immunoconjugates therapeutic use, Neoplasm Metastasis, Receptor, ErbB-2 metabolism, Trastuzumab administration & dosage, Trastuzumab therapeutic use
- Abstract
Competing Interests: We declare no competing interests.
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- 2024
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47. Numerical study of osteophyte effects on preoperative knee functionality in patients undergoing total knee arthroplasty.
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Tzanetis P, de Souza K, Robertson S, Fluit R, Koopman B, and Verdonschot N
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- Humans, Male, Female, Aged, Knee Joint physiopathology, Knee Joint surgery, Knee Joint diagnostic imaging, Middle Aged, Biomechanical Phenomena, Osteoarthritis, Knee surgery, Osteoarthritis, Knee physiopathology, Tomography, X-Ray Computed, Aged, 80 and over, Arthroplasty, Replacement, Knee, Osteophyte diagnostic imaging
- Abstract
Osteophytes are routinely removed during total knee arthroplasty, yet the preoperative planning currently relies on preoperative computed tomography (CT) scans of the patient's osteoarthritic knee, typically including osteophytic features. This complicates the surgeon's ability to anticipate the exact biomechanical effects of osteophytes and the consequences of their removal before the operation. The aim of this study was to investigate the effect of osteophytes on ligament strains and kinematics, and ascertain whether the osteophyte volume and location determine the extent of this effect. We segmented preoperative CT scans of 21 patients, featuring different osteophyte severity, using image-based active appearance models trained to identify the osteophytic and preosteophytic bone geometries and estimate the cartilage thickness in the segmented surfaces. The patients' morphologies were used to scale a template musculoskeletal knee model. Osteophytes induced clinically relevant changes to the knee's functional behavior, but these were variable and patient-specific. Generally, severe osteophytic knees significantly strained the oblique popliteal ligament (OPL) and posterior capsule (PC) relative to the preosteophytic state. Furthermore, there was a marked effect on the lateral collateral ligament and anterolateral ligament (ALL) strains compared to mild and moderate osteophytic knees, and concurrent alterations in the tibial lateral-medial translation and external-internal rotation. We found a strong correlation between the OPL, PC, and ALL strains and posterolateral condylar and tibial osteophytes, respectively. Our findings may have implications for the preoperative planning in total knee arthroplasty, toward reproducing the physiological knee biomechanics as close as feasibly possible., (© 2024 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)
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- 2024
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48. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.
- Author
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van der Kruijssen DEW, Elias SG, van de Ven PM, van Rooijen KL, Lam-Boer J', Mol L, Punt CJA, Sommeijer DW, Tanis PJ, Nielsen JD, Yilmaz MK, van Riel JMGH, Wasowiz-Kemps DK, Loosveld OJL, van der Schelling GP, de Groot JWB, van Westreenen HL, Jakobsen HL, Fromm AL, Hamberg P, Verseveld M, Jaensch C, Liposits GI, van Duijvendijk P, Oulad Hadj J, van der Hoeven JAB, Trajkovic M, de Wilt JHW, and Koopman M
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Denmark epidemiology, Netherlands epidemiology, Bevacizumab administration & dosage, Bevacizumab therapeutic use, Neoplasms, Multiple Primary surgery, Neoplasms, Multiple Primary pathology, Neoplasms, Multiple Primary drug therapy, Neoplasms, Multiple Primary mortality, Aged, 80 and over, Adult, Neoplasm Metastasis, Survival Rate, Colorectal Neoplasms pathology, Colorectal Neoplasms drug therapy, Colorectal Neoplasms surgery, Colorectal Neoplasms mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Background: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor., Patients and Methods: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098., Results: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm., Conclusions: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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49. Shortened radiofrequency delivery time to optimize efficiency and safety of pulmonary vein isolation with the radiofrequency balloon: insights from the COLLABORATE registry.
- Author
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Almorad A, Rocca DGD, Del Monte A, Vijgen J, Koopman P, Worck R, Johannessen A, Lepièce C, de Ravenstein AM, Strisciuglio T, Poggi S, Stabile G, La Greca C, Kheir JA, Jesel-Morel L, El Haddad M, Hossein A, Audiat C, Scacciavillani R, Pannone L, de Asmundis C, and Chierchia GB
- Subjects
- Humans, Female, Male, Middle Aged, Treatment Outcome, Aged, Europe, Time Factors, Prospective Studies, Cardiac Catheters, Recurrence, Risk Factors, Pulmonary Veins surgery, Registries, Catheter Ablation methods, Catheter Ablation adverse effects, Atrial Fibrillation surgery, Atrial Fibrillation diagnosis
- Abstract
Aims: Previous clinical studies on pulmonary vein isolation (PVI) with a radiofrequency balloon (RFB) reported safe and effective procedures using conventional ablation settings with 20/60 s RF delivery via posterior/anterior (PST/ANT) electrodes. The latest evidence suggests that reducing the application time to 15 s (s) on the posterior wall when facing the oesophageal region is as effective as applying 20 s. To prospectively assess whether reducing RF time on PST/ANT segments to 15/45 s can ensure sufficient quality of lesion metrics and compare the new shortened ablation settings with the conventional one in terms of safety, and effectiveness at 1-year., Methods and Results: A total of 641 patients from seven European centres were enrolled in a collaborative registry, with 374 in the conventional RF delivery group and 267 in the shortened RF delivery group. Procedural outcomes, lesion metrics, and safety profiles were assessed and compared between the groups. Freedom of any atrial tachycarrythmias at one year was 85.4% and 88.2% in the SHRT and CONV groups, respectively. The shortened RF delivery strategy was associated with significantly shorter procedure times (median 63.5 vs. 96.5 min, P < 0.001) and shortened fluoroscopy exposure (median 10.0 vs. 14.0 min, P < 0.001) compared to conventional delivery. Efficacy metrics, including first-pass isolation rates and time to isolation, were comparable between groups. Shortened RF delivery was associated with a lower incidence of procedural complications (1.4% vs. 5.3%, P = 0.04) and optimized thermal characteristics., Conclusion: Analyses from the COLLABORATE registry demonstrate that shortening RF energy delivery times to 15/45 s (PST/ANT) during PVI with the RFB resulted in comparable freedom from recurrent atrial tachyarrhythmia compared to conventional delivery times with comparable efficiency and safety., Competing Interests: Conflict of interest: A.A. received institutional compensation for teaching and proctoring from Medtronic, Abbott, Boston Scientific, and Biosense Webster. G.-B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. received research grants from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; C.d.A. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo. The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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50. Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia.
- Author
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Westerveld ASR, Roesthuis P, van der Pal HJH, Bresters D, Bierings M, Loonen J, de Vries ACH, Louwerens M, Koopman MMW, van den Heuvel-Eibrink MM, van der Heiden-van der Loo M, Hoogerbrugge P, Janssens GO, de Krijger RR, Ronckers CM, Pieters R, Kremer LCM, and Teepen JC
- Subjects
- Humans, Male, Female, Child, Child, Preschool, Adolescent, Risk Factors, Infant, Adult, Incidence, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary etiology, Cancer Survivors statistics & numerical data
- Abstract
Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963-2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5-5.3) for SMNs and 10.4%(95%CI: 8.9-12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1-3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3-7.9), and without TBI (HR:4.0,95%CI: 1.2-13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4-4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors., (© 2024. The Author(s).)
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- 2024
- Full Text
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