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Article ; Online: A MYC-rearrangement is a negative prognostic factor in stage II, but not in stage I diffuse large B-cell lymphoma.

de Jonge, A V / Bult, J A A / Karssing, D F E / Nijland, M / Chamuleau, M E D / Brink, M

2024 Volume 14, Issue 1, Page(s) 2

Abstract: MYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III-IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I-II is unclear. Therefore, we assessed the impact of MYC-R on ... ...

Abstract	MYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III-IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I-II is unclear. Therefore, we assessed the impact of MYC-R on progression-free survival (PFS) and overall survival (OS) in LS DLBCL patients at the population level. We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022. Stage I patients with (n = 83, 11%) and without (n = 650, 89%) a MYC-R had similar 2-years PFS (89% and 93%, p = 0.63) and OS (both 95%, p = 0.22). Conversely, stage II DLBCL patients with a MYC-R (n = 90, 13%) had inferior survival outcomes compared to stage II patients without a MYC-R (n = 611, 87%) (PFS 70% vs. 89%, p = 0.001; OS 79% vs. 94%, p < 0.0001). Both single MYC-R (single hit, n = 36) and concurrent BCL2 and/or BCL6 rearrangements (double/triple hit, n = 39) were associated with increased mortality and relapse risk. In conclusion, in stage II DLBCL a MYC-R is negatively associated with survival. In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.
MeSH term(s)	Humans ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-bcl-6 ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/genetics ; Doxorubicin/therapeutic use
Chemical Substances	Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-myc ; Proto-Oncogene Proteins c-bcl-6 ; Doxorubicin (80168379AG)
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-023-00971-y
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Article: Increased fT4 concentrations in patients using levothyroxine without complete suppression of TSH.

Jansen, Heleen I / Bult, Marijn M / Bisschop, Peter H / Boelen, Anita / Heijboer, Annemieke C / Hillebrand, Jacquelien J

Endocrine connections

2023 Volume 12, Issue 4

Abstract: Introduction: In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samples of patients at the outpatient clinic, which appeared to occur more often ... ...

Abstract	Introduction: In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samples of patients at the outpatient clinic, which appeared to occur more often following the introduction of a new fT4 immunoassay. This discordance may be explained by incorrect reference intervals, analytical issues, or patient-related factors. We aimed to establish the contribution of the possible factors involved. Methods: Reference intervals of both fT4 immunoassays were re-evaluated using blood samples of healthy volunteers and the new immunoassay's performance was assessed using internal quality controls and external quality rounds. The frequency of discordant fT4 and TSH pairings obtained from laboratory requests were retrospectively analysed using a Delfia (n = 3174) and Cobas cohort (n = 3408). Last, a literature search assessed whether the time of blood draw and the time of levothyroxine (L-T4) ingestion may contribute to higher fT4 concentrations in L-T4 users. Results: The original reference intervals of both fT4 immunoassays were confirmed and no evidence for analytical problems was found. The Delfia (n = 176, 5.5%) and Cobas cohorts (n = 295, 8.7%) showed comparable frequencies of discordance. Interestingly, 72-81% of the discordant results belonged to L-T4 users. Literature indicated the time of blood withdrawal of L-T4 users and, therefore, the time of L-T4 intake as possible explanations. Conclusions: High fT4 without suppressed TSH concentrations can mainly be explained by L-T4 intake. Physicians and laboratory specialists should be aware of this phenomenon to avoid questioning the assay's performance or unnecessarily adapting the L-T4 dose in patients.
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2668428-7
ISSN	2049-3614
ISSN	2049-3614
DOI	10.1530/EC-22-0538
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Article ; Online: US and Digital Breast Tomosynthesis in Women with Focal Breast Complaints: Results of the Breast US Trial (BUST).

Appelman, Linda / Siebers, Carmen C N / Appelman, Peter T M / Go, H L Shirley / Broeders, Mireille J M / van Oirsouw, Marja C J / Bult, Peter / Mann, Ritse M

Radiology

2023 Volume 307, Issue 4, Page(s) e220361

Abstract: Background Digital breast tomosynthesis (DBT) followed by targeted US is commonly performed to evaluate women with localized breast complaints. However, the added value of DBT in addition to targeted US is unknown. Omitting DBT may be cost-effective and ... ...

Abstract	Background Digital breast tomosynthesis (DBT) followed by targeted US is commonly performed to evaluate women with localized breast complaints. However, the added value of DBT in addition to targeted US is unknown. Omitting DBT may be cost-effective and improve patient comfort but may miss potential breast cancer. Purpose To assess whether an imaging protocol consisting of targeted US alone may be feasible for the diagnostic work-up of women with localized symptoms and to assess the supplemental value of DBT in this reversed setting. Materials and Methods This prospective study enrolled consecutive women aged 30 years or older with focal breast complaints in three hospitals in the Netherlands between September 2017 and June 2019. In all participants, first, targeted US was evaluated, and if needed, biopsy was performed, followed by DBT. The primary outcome was the frequency of breast cancer detected with DBT when US was negative. Secondary outcomes were frequency of cancer detected with DBT elsewhere in the breast and combined overall sensitivity of US plus DBT. The reference standard was 1 year follow-up or histopathologic examination. Results There were 1961 women (mean age ± SD, 47 years ± 12) enrolled. Based on initial US alone, 1587 participants (81%) had normal or benign findings and 1759 (90%) had a definitive accurate diagnosis. In total, 204 breast cancers were detected during initial work-up. The frequency of malignancy was 10% (192 of 1961 participants) with US (US sensitivity, 98.5% [95% CI: 96, 100]; US specificity, 90.8% [95% CI: 89, 92]). DBT depicted three unobserved malignant lesions at the complaint site and 0.41% (eight of 1961 participants) of incidental malignant findings in participants without symptomatic cancer. Conclusion Compared with combined US and DBT, US was accurate as a stand-alone breast imaging modality in the assessment of focal breast complaints. The rate of cancer detection of cancers elsewhere in the breast with DBT is comparable to cancer detection rate of screening mammography. © RSNA, 2023
MeSH term(s)	Female ; Humans ; Mammography/methods ; Breast Neoplasms/pathology ; Prospective Studies ; Early Detection of Cancer/methods ; Breast/diagnostic imaging ; Breast/pathology
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80324-8
ISSN	1527-1315 ; 0033-8419
ISSN (online)	1527-1315
ISSN	0033-8419
DOI	10.1148/radiol.220361
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Article ; Online: Functional impact of a germline RET mutation in alveolar rhabdomyosarcoma.

Berlow, Noah E / Crawford, Kenneth A / Bult, Carol J / Noakes, Christopher / Sloma, Ido / Rudzinski, Erin R / Keller, Charles

Cold Spring Harbor molecular case studies

2021 Volume 7, Issue 3

Abstract: Specific mutations in ... ...

Abstract	Specific mutations in the
MeSH term(s)	Animals ; Cell Line, Tumor ; DNA Mutational Analysis ; Genotype ; Germ Cells/physiology ; Germ-Line Mutation ; Humans ; Mice ; Multiple Endocrine Neoplasia Type 2a/genetics ; Multiple Endocrine Neoplasia Type 2a/pathology ; Phenotype ; Proto-Oncogene Proteins c-ret/genetics ; Proto-Oncogene Proteins c-ret/metabolism ; Rhabdomyosarcoma, Alveolar/drug therapy ; Rhabdomyosarcoma, Alveolar/genetics ; Xenograft Model Antitumor Assays
Chemical Substances	Proto-Oncogene Proteins c-ret (EC 2.7.10.1) ; RET protein, human (EC 2.7.10.1)
Language	English
Publishing date	2021-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2835759-0
ISSN	2373-2873 ; 2373-2873
ISSN (online)	2373-2873
ISSN	2373-2873
DOI	10.1101/mcs.a006049
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Article ; Online: Trough anti-Xa activity after intermediate dose nadroparin for thrombosis prophylaxis in critically ill patients with COVID-19 and acute kidney injury.

Eck, R J / van de Leur, J J C M / Wiersema, R / Cox, E G M / Bult, W / Spanjersberg, A J / van der Horst, I C C / Lukens, M V / Gans, R O B / Meijer, K / Keus, F

Scientific reports

2022 Volume 12, Issue 1, Page(s) 17408

Abstract: Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. ...

Abstract	Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.
MeSH term(s)	Humans ; Nadroparin/adverse effects ; Critical Illness ; Prospective Studies ; COVID-19/complications ; Anticoagulants/therapeutic use ; Acute Kidney Injury ; Thrombosis/prevention & control
Chemical Substances	Nadroparin ; Anticoagulants
Language	English
Publishing date	2022-10-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-21560-2
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Article ; Online: Subpar reporting of pre-analytical variables in RNA-focused blood plasma studies.

Van Der Schueren, Céleste / Decruyenaere, Philippe / Avila Cobos, Francisco / Bult, Johanna / Deleu, Jill / Dipalo, Laudonia Lidia / Helsmoortel, Hetty Hilde / Hulstaert, Eva / Morlion, Annelien / Ramos Varas, Elena / Schoofs, Kathleen / Trypsteen, Wim / Vanden Eynde, Eveline / Van Droogenbroeck, Hanne / Verniers, Kimberly / Vandesompele, Jo / Decock, Anneleen

Molecular oncology

2024

Abstract: Extracellular RNA (cell-free RNA; exRNA) from blood-derived liquid biopsies is an appealing, minimally invasive source of disease biomarkers. As pre-analytical variables strongly influence exRNA measurements, their reporting is essential for meaningful ... ...

Abstract	Extracellular RNA (cell-free RNA; exRNA) from blood-derived liquid biopsies is an appealing, minimally invasive source of disease biomarkers. As pre-analytical variables strongly influence exRNA measurements, their reporting is essential for meaningful interpretation and replication of results. The aim of this review was to chart to what extent pre-analytical variables are documented, to pinpoint shortcomings and to improve future reporting. In total, 200 blood plasma exRNA studies published in 2018 or 2023 were reviewed for annotation of 22 variables associated with blood collection, plasma preparation, and RNA purification. Our results show that pre-analytical variables are poorly documented, with only three out of 22 variables described in over half of the publications. The percentage of variables reported ranged from 4.6% to 54.6% (mean 24.84%) in 2023 and from 4.6% to 57.1% (mean 28.60%) in 2018. Recommendations and guidelines (i.e., BRISQ, ASCO-CAP, BloodPAC, PPMPT, and CEN standards) have currently not resulted in improved reporting. In conclusion, our results highlight the lack of reporting pre-analytical variables in exRNA studies and advocate for a consistent use of available standards, endorsed by funders and journals.
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13647
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Zs.A 6637: Show issues

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Article ; Online: Cancer-associated mesothelial cells are regulated by the anti-Müllerian hormone axis.

Chauvin, M / Meinsohn, M-C / Dasari, S / May, P / Iyer, S / Nguyen, N M P / Oliva, E / Lucchini, Z / Nagykery, N / Kashiwagi, A / Mishra, R / Maser, R / Wells, J / Bult, C J / Mitra, A K / Donahoe, Patricia K / Pépin, D

Cell reports

2023 Volume 42, Issue 7, Page(s) 112730

Abstract: Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Müllerian hormone (AMH) while CAMCs express its ... ...

Abstract	Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Müllerian hormone (AMH) while CAMCs express its receptor AMHR2, suggesting a paracrine axis. Factors secreted by cancer cells induce AMHR2 expression during their reprogramming into CAMCs in mouse and human in vitro models. Overexpression of AMHR2 in the Met5a mesothelial cell line is sufficient to induce expression of immunosuppressive cytokines and growth factors that stimulate ovarian cancer cell growth in an AMH-dependent way. Finally, syngeneic cancer cells implanted in transgenic mice with Amhr2
MeSH term(s)	Female ; Humans ; Animals ; Mice ; Anti-Mullerian Hormone/genetics ; Ovarian Neoplasms/genetics ; Peptide Hormones ; Mice, Transgenic ; Receptors, Transforming Growth Factor beta/metabolism ; Tumor Microenvironment
Chemical Substances	Anti-Mullerian Hormone (80497-65-0) ; Peptide Hormones ; Receptors, Transforming Growth Factor beta
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112730
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Article: From information to understanding: the role of model organism databases in comparative and functional genomics.

Bult, C J

Animal genetics

2006 Volume 37 Suppl 1, Page(s) 28–40

Abstract: Data integration is key to functional and comparative genomics because integration allows diverse data types to be evaluated in new contexts. To achieve data integration in a scalable and sensible way, semantic standards are needed, both for naming ... ...

Abstract	Data integration is key to functional and comparative genomics because integration allows diverse data types to be evaluated in new contexts. To achieve data integration in a scalable and sensible way, semantic standards are needed, both for naming things (standardized nomenclatures, use of key words) and also for knowledge representation. The Mouse Genome Informatics database and other model organism databases help to close the gap between information and understanding of biological processes because these resources enforce well-defined nomenclature and knowledge representation standards. Model organism databases have a critical role to play in ensuring that diverse kinds of data, especially genome-scale data sets and information, remain useful to the biological community in the long-term. The efforts of model organism database groups ensure not only that organism-specific data are integrated, curated and accessible but also that the information is structured in such a way that comparison of biological knowledge across model organisms is facilitated.
MeSH term(s)	Animals ; Computational Biology ; Databases, Genetic ; Genomics/methods ; Humans ; Mice/genetics ; Models, Animal ; Phenotype ; Terminology as Topic
Language	English
Publishing date	2006-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632766-7
ISSN	1365-2052 ; 0268-9146 ; 0268-9154
ISSN (online)	1365-2052
ISSN	0268-9146 ; 0268-9154
DOI	10.1111/j.1365-2052.2006.01475.x
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Zs.B 1688: Show issues

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Article ; Online: A fast and simple method for the simultaneous analysis of midazolam, 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, plasma and urine.

Wessels, A Mireille A / Bolhuis, Mathieu S / Bult, Wouter / Nijsten, Maarten W N / Kneyber, Martin C J / Touw, Daan J

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2020 Volume 1162, Page(s) 122476

Abstract: ... on a C ...

Abstract	For the quantification of the sedative and anesthetic drug midazolam and its main (active) metabolites 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, human EDTA plasma, human heparin plasma and human urine a single accurate method by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed. Protein precipitation as sample preparation, without the need of a time-consuming deglucuronidation step for the quantification of 1-hydroxymidazolam glucuronide, resulted in a simple and rapid assay suitable for clinical practice with a total runtime of only 1.1 min. The four components and the isotope-labeled internal standards were separated on a C
MeSH term(s)	Aged ; Chromatography, High Pressure Liquid/methods ; Drug Stability ; Female ; Humans ; Infant, Newborn ; Limit of Detection ; Linear Models ; Midazolam/analogs & derivatives ; Midazolam/blood ; Midazolam/pharmacokinetics ; Midazolam/urine ; Reproducibility of Results ; Tandem Mass Spectrometry/methods
Chemical Substances	Midazolam (R60L0SM5BC)
Language	English
Publishing date	2020-12-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2020.122476
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Article ; Online: Histological subtypes in triple negative breast cancer are associated with specific information on survival.

Balkenhol, Maschenka C A / Vreuls, Willem / Wauters, Carla A P / Mol, Suzanne J J / van der Laak, Jeroen A W M / Bult, Peter

Annals of diagnostic pathology

2020 Volume 46, Page(s) 151490

Abstract: Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to ... ...

Abstract	Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC. A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed. Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18-3.03; p = 0.008; OS HR 1.94; 95% CI 1.28-2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes. In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Triple Negative Breast Neoplasms/mortality ; Triple Negative Breast Neoplasms/pathology
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	1440011-x
ISSN	1532-8198 ; 1092-9134
ISSN (online)	1532-8198
ISSN	1092-9134
DOI	10.1016/j.anndiagpath.2020.151490
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