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Dirk Timmerman

Dirk Timmerman
KU Leuven | ku leuven · Department of Development and Regeneration

Professor

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857
Publications
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23,252
Citations

Publications

Publications (857)
Article
Background: Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis, and monitoring. We hypothesized that mining the patterns of cfDNA shallow whole-genome sequencing datasets from patients with cancer could improve cancer detection. Methods: By applying unsupervised clustering and supervised machine learn...
Article
Full-text available
Objective: Methods to correct class imbalance (imbalance between the frequency of outcome events and nonevents) are receiving increasing interest for developing prediction models. We examined the effect of imbalance correction on the performance of logistic regression models. Material and methods: Prediction models were developed using standard...
Article
Objectives: To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) to predict ovarian endometriomas (OE), overall deep endometriosis (DE), and DE locations by following the International Deep Endometriosis Analysis (IDEA) consensus statement. Methods: This was an international, multicenter prospective diagnostic accuracy study invo...
Article
Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling was subsequently applied to capture...
Article
Objectives: The primary aim is to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim is to compare our findings with published data on women with AUB. Methods: Patients...
Article
Full-text available
Objectives To investigate prognostic factors for anxiety, depression and post-traumatic stress (PTS) symptoms 1 month after early pregnancy loss (EPL). Design A prospective cohort study. Consecutive women were recruited, and demographic and clinical data were collected. Surveys containing the Hospital Anxiety and Depression Scale (HADS) and Post-t...
Article
Research question Is there a difference in recurrence rate of endometrioma(s) after cystectomy versus CO2-laser vaporization of the cyst wall. Design This single center retrospective study included 270 patients undergoing laparoscopic surgery for endometriomas between January 2010 and December 2014, stratified according to the surgical technique u...
Article
Objectives: To describe the clinical and ultrasound features of ovarian mature cystic teratomas (MCTs). Methods: This is a retrospective analysis of data in the International Ovarian Tumor Analysis (IOTA) database. We included those patients with a histologically confirmed diagnosis of MCT that had been examined with ultrasound between 1999 and...
Article
Measuring vascularization in uterine fibroids is important for their diagnosis, treatment and prognosis. Vascularization can be measured by power Doppler ultrasound. The power Doppler signal depends on fibroid characteristics and on a variety of ultrasound-machine settings. Literature describing which machine settings influence the power Doppler si...
Preprint
Background Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis and monitoring. We hypothesized that mining the patterns of big datasets of shallow whole genome sequencing cfDNA from cancer patients could improve cancer detection. Methods By applying unsupervised clustering and supervised machine learning...
Preprint
Full-text available
Methods to correct class imbalance, i.e. imbalance between the frequency of outcome events and non-events, are receiving increasing interest for developing prediction models. We examined the effect of imbalance correction on the performance of standard and penalized (ridge) logistic regression models in terms of discrimination, calibration, and cla...
Article
Objectives: To develop a model that can discriminate between different etiologies of abnormal uterine bleeding. Design: The International Endometrial Tumor Analysis (IETA) 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound exami...
Article
Full-text available
Objective: Assess experience of healthcare professionals (HCPs) working with ultrasound in obstetrics and gynaecology during the evolving SARS-CoV-2 pandemic, given the new and unprecedented challenges involving viral exposure, personal protective equipment (PPE) and well-being. Design: Prospective cross-sectional survey study. Setting: Online...
Article
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Introduction: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and β human chorionic gonadotropin (βhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value...
Article
Full-text available
In monotherapy, immunotherapy has a poor success rate in ovarian cancer. Upgrading to a successful combinatorial immunotherapy treatment implies knowledge of the immune changes that are induced by chemotherapy and surgery. Methodology: Patients with a new d ovarian cancer diagnosis underwent longitudinal blood samples at different time points dur...
Article
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Background: Tumors can influence peripheral immune macroenvironment, thereby creating opportunities for non-invasive serum/plasma immunobiomarkers for immunostratification and immunotherapy designing. However, current approaches for immunobiomarkers’ detection are largely quantitative, which is unreliable for assessing functional peripheral immunod...
Article
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Objective: To develop a standardized sonographic evaluation and reporting system for a cesarean scar pregnancy (CSP) in the first trimester for both general gynecology and expert clinic. Methods: A modified Delphi procedure. Twenty-eight experts in obstetrics and gynecology ultrasonography were invited to participate. Extensive experience in the...
Article
Background: Clinical models to predict first trimester viability are traditionally based on multivariable logistic regression (LR) which is not directly interpretable for non-statistical experts like physicians. Furthermore, LR requires complete datasets and pre-established variables specifications. In this study, we leveraged the internal non-line...
Conference Paper
Introduction/Background* Cancer organoids are an emerging in vitro tool to study tumorigenesis.However, patient-specific applications, s. a. chemotherapy response prediction, remain understudied. Organoid protocols vary considerably between different publications, impeding clinical applications. Our aim was to examine the experimental design charac...
Article
Full-text available
Objective: To update the Morphological Uterus Sonographic Assessment (MUSA) definitions of adenomyosis if deemed necessary, and to reach consensus on the updated definitions METHODS: A modified Delphi procedure among European gynecologists with expertise in ultrasound diagnosis of adenomyosis was performed. To identify MUSA features that might nee...
Article
Study question Is there an association between serum oestradiol, vaginal microbial composition and pregnancy outcome in the early first trimester? Summary answer In women with a vaginal microbiome deplete of Lactobacillus species at the time of Pregnancy of Uncertain Viability (IPUV), higher serum oestradiol associates with livebirth. What is kno...
Article
Objectives: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. Methods: This is a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database we identified 24 patients with a histological diagnosis of ovarian carcinosarcoma who had undergone preoperative ultrasound examination be...
Article
Full-text available
The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of...
Article
Full-text available
The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis...
Article
The current review sums up the literature on the diagnostic performance of models to predict malignancy in adnexal masses and the ability of ultrasound to make a specific diagnosis in adnexal masses. A summary of the role of ultrasound in assessing the extension of malignant ovarian disease is also provided.
Article
Full-text available
Context Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility. Objective This proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS. Design This was a phase 2a, randomized,...
Article
Full-text available
The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis group (IOTA) and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence‐based consensus statements on the pre‐operative d...
Article
Objective To assess the safety, adequacy and accuracy of transvaginal ultrasound-guided tru-cut biopsy of pelvic masses. Methods We performed a retrospective analysis of consecutive women who underwent transvaginal ultrasound-guided tru-cut biopsies between June 2014 and October 2018 at the Department of Obstetrics and Gynecology of the University...
Article
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The pelviperineal organs of the female reproductive tract form an essential cornerstone of human procreation. The system comprises the ectodermal external genitalia, the Müllerian upper-vaginal, cervical, endometrial and oviductal derivatives, and the endodermal ovaries. Each of these organs presents with a unique course of biological development a...
Article
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Background We suggest an adaptive sample size calculation method for developing clinical prediction models, in which model performance is monitored sequentially as new data comes in. Methods We illustrate the approach using data for the diagnosis of ovarian cancer ( n = 5914, 33% event fraction) and obstructive coronary artery disease (CAD; n = 48...
Article
Human drug research, and cancer drug research in particular, heavily relies on traditional tumour models such as 2D cell cultures and xenografts to develop and test novel therapeutics. Organoids are a novel 3D cell platform derived from stem cells, allowing to faithfully replicate human tissue in an in vitro environment, bridging the ease of use of...
Article
Significant successes in machine learning approaches to image analysis for various applications have energized strong interest in automated diagnostic support systems for medical images. The evolving in-depth understanding of the way carcinogenesis changes the texture of cellular networks of a mass/tumor has been informing such diagnostics systems...
Article
Full-text available
Objective: To externally validate five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). Design: Secondary analysis of a prospective coho...
Article
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Response to: Correspondence on "ESGO/ISUOG/IOTA/ ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors" by Thomassin-Nagarra et al We thank Isabelle Thomassin-Nagarra et al for their interest in the ESGO/ISUOG/ IOTA/ESGE consensus statement on the pre-operative diagnosis of ovarian tumors. This statement is based on a careful review...
Article
Study question: Can the Endometriosis Fertility Index (EFI) be estimated accurately before surgery? Summary answer: The EFI can be estimated accurately based on mere clinical/ultrasound information, with some improvement after adding data from diagnostic laparoscopy. What is known already: The EFI is a validated clinical instrument predicting...
Article
Full-text available
Objectives: The aim of this systematic review is to examine the use of telemedicine in the delivery and teaching of gynaecological clinical practice. To our knowledge, no other systematic review has assessed this broad topic. Design: Systematic review of all studies investigating the use of telemedicine in the provision of gynaecological care and...
Article
Full-text available
Uterine cancer is the most and second most common gynecological malignancy in developed and developing countries, respectively. The majority of endometrial cancers are diagnosed early due to the presence of abnormal uterine bleeding. The existing literature however contains only little data regarding the prevalence of such symptoms compared to pati...
Article
Objective: To describe the clinical and ultrasound characteristics of three rare malignant ovarian germ cell tumors: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. Methods: This is a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified seven patie...
Conference Paper
Full-text available
Objectives To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) to predict overall deep endometriosis (DE) and DE locations by applying the IDEA terminology. Methods This was an international, multicentre prospective diagnostic accuracy study involving 9 centres across 6 countries (Aug 2018‐Nov 2019). Consecutive participants were...
Preprint
Full-text available
Background: We suggest an adaptive sample size calculation method for developing clinical prediction models, in which model performance is monitored sequentially as new data comes in. Methods: We illustrate the approach using data for the diagnosis of ovarian cancer (n=5914, 33% event fraction) and obstructive coronary artery disease (CAD; n=4888,...
Article
Objectives: To investigate and compare post-traumatic stress (PTS), depression and anxiety in women and their partners over a 9-month period following miscarriage or ectopic pregnancy. Methods: This was a prospective cohort study. Consecutive women and their partners were approached in the early pregnancy units of three hospitals in central Lond...
Article
Objective: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. Methods: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospita...
Article
Full-text available
Objectives: The aim was to assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second stage test in difficult adnexal masses. Methods: This is a prospective observational international multicenter diagnostic accuracy study. 2403 consecu...
Article
Full-text available
Objective To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. Design Multicentre cohort study. Setting 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. Participants Consec...
Article
Full-text available
Germline pathogenic alterations in the breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the most prevalent causes of hereditary breast and ovarian cancer. The increasing trend in proportion of cancer patients undergoing genetic testing, followed by predictive testing in families of new index patients, results in a significant increase...
Article
Multiple measurements of serum human chorionic gonadotropin (hCG) are used to predict the final pregnancy outcome for women with a pregnancy of unknown location (PUL) and monitor the management of ectopic pregnancy (EP). Urine-based testing would be more convenient and economical. This prospective cohort study involving 80 women assessed the degree...
Article
Objective: To describe the ultrasound features of different endometrial and other intracavitary pathologies in pre- and postmenopausal women presenting with abnormal uterine bleeding using the International Endometrial Tumor Analysis (IETA) terminology. Methods: Prospective observational multicenter study of 2856 consecutive women presenting wit...
Article
Full-text available
Ovarian cancer (OC) represents the most dismal gynecological cancer. Pathobiology is poorly understood, mainly due to lack of appropriate study models. Organoids, defined as self-developing three-dimensional in vitro reconstructions of tissues, provide powerful tools to model human diseases. Here, we established organoid cultures from patient-deriv...