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52. Contributors

Author

Abascal, Faustino A., Adams, Judith E., Adler, Ronald S., Ahn, Joong Mo, Albareda, Jorge Albareda, Ali, Sana, Allen, Gina M., Anavim, Arash, Anderson, Mark W., Anderson, Suzanne E., Aparisi, Francisco, Gómez, Pilar Aparisi, Armfield, Derek R., Atkins, Bridget, Baker, Jonathan C., Ballehr, Lisa O., Baltazar, Romulo, Bancroft, Laura, Barker, Chad H., Barr, Michelle A., Baur-Melnyk, Andrea, Beaman, Francesca, Beltran, Javier, Beltran, Luis S., Bencardino, Jenny T., Blankenbaker, Donna G., Bloem, Hans L., Bolster, Marcy B., Borghei, Peyman, Boulet, Cedric, Brouwer, Patrick A., Brown, Elliott, Bueno, Ángel, Calleja, Michele, Canga, Ana, Cardoso, Fabiano Nassar, Cassar-Pullicino, Victor, de Albuquerque, Conrado Furtado, Cerezal, Luis, Chapin, Russell W., Chen, Qi, Cheung, Yvonne Y., Cho, Aaron, Chundru, Kishore K., Chundru, Usha, Chung, Christine B., Coggins, Claire, Cruz, Antonio, Czerny, Christian, Daffner, Richard H., D'Anastasi, Melvin, Davies, A. Mark, Davis, Kirkland W., de Jonge, Milko C., De, Michel O., De Schepper, Arthur, Sr., Luis, José, Delman, Bradley N., Dheer, Sachin, Dieudonné, Grégory, Dobtsis, Joseph, Doherty, Brendan T., Dominguez, Rodrigo, Donati, Davide Maria, Döring, Seema, Dorshi, Nimisha, Douis, Hassan, Dzirkale, Aija, El-Khoury, Georges Y., Eņǵele, Ilze, Hualde, Ana M., Epermane, Mara, Fang, Christopher J., Fayad, Laura M., Finden, Steven, Flemming, Donald J., Freyschmidt, Jürgen, Gielen, Jan L., Gopez, Angela Gessner, Gorbachova, Tetyana, Grainger, Andrew J., Haims, Andrew H., Hanono, Joseph, Hant, Faye N., Harris, John H., Jr., Hayes, Curtis W., Haygood, Tamara Miner, Higueras, Victoria, Hofmann, Siegfried, Hrehorovich, Peter, Hsieh, Maya Sardjono, Huysse, Wouter C.J., Ilaslan, Hakan, Jablonka, Karsten, Jafarian, Neda, James, Steven L.J., Johnson, Ann M., Johnson, Karl, Johnson, Maria Bernadette, Karantanas, Apostolos, Karasick, David, Katsivas, Theodoros F., Kavanagh, Eoin C., Keats, Theodore E., Khan, Shah H.M., Kheyfits, Valeriy, Konin, Gabrielle P., Koulouris, George, Kramer, Josef, Kransdorf, Mark J., Kroon, Herman M., Kwait, Dylan C., Lalam, Radhesh, Lardenoije, Susanne W.Y., Ledermann, Hans P., Lenobel, Scott S., Liu, Brandon Y., Llopis, Eva, Loeys, Bart, Logie, Chika Iloanusi, Long, Niamh M., Ma, Calvin, Malghem, Jacques, Marks, Natalia, Martel, José, Mathew, Manesh, McCall, Iain W., McNally, Eugene, Mellado, José M., Menn, Kirsten A., Miller, Theodore T., Mintz, Douglas N., Monu, Johnny U.V., Moore, Sandra, Morcos, Morcos, Morrison, William B., Mortier, Geert R., Mosher, Timothy J., Mulligan, Michael E., Murphey, Mark D., Murphy, William A., Jr., Nazarenko, Anna, Neilande, Elina, Nissman, Daniel B., Offiah, Amaka C., Oh, Richard, Omar, Imran M., Omoumi, Patrick, Opsha, Oleg, Ostlere, Simon, Owen, Joshua, Padron, Mario, Paruchuri, Narayan Babu, Pfirrmann, Christian W.A., Pharoah, Michael J., Philippon, Marc J., Pope, Thomas L., Jr., Probyn, Linda, Raeymaeckers, Steven, Rankine, James J., Rao, Anil G., Rao, Nisha, Rider, Lisa G., Roberts, Catherine C., Robinson, Philip, Rogers, Lee F., Rolón, Alejandro U., Rosenbloom, Lorne, Rosenthal, Daniel I., Rubin, David A., Salgado, Rodrigo A., Schenk, Barry, Scheurecker, Anna, Schils, Jean, Schorn, Corinna, Schwarting, Andreas, Schweitzer, Mark E., Sekiya, Jon K., Shahabpour, Maryam, Shankar, Prashant V., Shankman, Steven, Smith, Roger, Snoeckx, Annemie, Snyder, Travis G., Som, Peter M., Spouge, Alison R., Sprigg, Alan, Stein, Evan G., Steinbach, Lynne S., Sundaram, Murali, Taljanovic, Mihra S., Teh, James, Tehranzadeh, Jamshid, Teixeira Neto, Afranio dos Reis, Terra, Maaike P., Tins, Bernhard, Tshering, Dechen Wangmo, Tuite, Michael J., Umans, Hilary R., Uri, Ishaq Fahmi, van Erkel, Arian R., van Rijswijk, Carla, Berg, Bruno Vande, Vanhoenacker, Filip M., Verstraete, Koenraad L., Walker, Eric A., Watt, Iain, White, Lawrence M., Williams, Helen, Willits, Kevin R., Wilson, David J., Yamashita, Samia R., Yao, Lawrence, Yu, Joseph S., Zelenko, Natalie, Zlatkin, Michael B., and Zoga, Adam C.

Published
2015
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53. Value of [11C]-methionine PET/CT in preoperative localization of adenomas in primary hyperparathyroidism

Author

Keyaerts Marleen, Bravenboer Bert, Saerens Julie, Raeymaeckers Steven, Velkeniers Brigitte, Vanhoeij Marian, Faculty of Medicine and Pharmacy, Clinical sciences, Internal Medicine, Surgical clinical sciences, Surgery, Supporting clinical sciences, Medical Imaging, Nuclear Medicine, Basic (bio-) Medical Sciences, Radiology, Gerontology, and Geriatrics

Subjects
endocrine system diseases, business.industry, 11c methionine pet, medicine, medicine.disease, business, Nuclear medicine, Value (mathematics), Primary hyperparathyroidism
Abstract

Introduction: The first-line imaging modalities to locate adenomas preoperatively in primary hyperparathyroidism (PHPT) are ultrasonography (US) and subtraction scintigraphy (SuSc). When these contradict each other or are inconclusive an [11C]-methionine PET/CT (MET-PET/CT) or a 4-dimensional computed tomography (4D-CT) can be performed. Objectives: The aim of this retrospective study was to evaluate the value of MET-PET/CT in the preoperative localization of adenomas in PHPT, especially when US and/or SuSc were inconclusive or negative. Methods: All patients that underwent parathyroidectomy in the UZ Brussel in the period of 01-01-2008 until 31-12-2017 (10 years) for hyperparathyroidism were selected with exclusion of secondary and tertiary hyperparathyroidism, renal insufficiency (CKD stage 3B or worse), MEN syndrome and known malignancy. Finally, 84 patients were included. The results of US, SuSc, MET-PET/CT and 4D-CT were correlated to intraoperative decline in parathyroid hormone (PTH) levels and to the anatomopathological analysis. Sensitivity and specificity were calculated per-lesion for each imaging modality. Results: 75 patients (89%) had a single parathyroid adenoma and nine patients (11%) had multiglandular PHPT (four patients had two adenomas, and five patients had hyperplasia). Not every patient underwent every imaging modality: 75 (90 adenomas), 62 (75 adenomas), 16 (22 adenomas) and 8 (8 adenomas) patients underwent respectively US, SuSc, MET-PET/CT and 4D-CT. The observed per-lesion sensitivity of US, SuSc, MET-PET/CT and 4D-CT is respectively 40.0%, 32.0%, 59.1% and 62.5%. The observed per-lesion specificity of US, SuSc, MET-PET/CT and 4D-CT is respectively 95.5%, 91.4%, 95.7% and 96.0%. Due to the limited sample size, especially in 4D-CT, the 95%-Clopper Pearson confidence intervals are large and therefore difficult to interpret. A sub-analysis on paired data only between two imaging modalities with a McNemar test showed a significant better per-lesion sensitivity of MET-PET/CT compared to US (P=0.039) and a significant higher per-lesion specificity of US compared to SuSc (P=0.035). The difference in per-lesion sensitivity between MET-PET/CT and SuSc showed a P-value of 0.070. In 70% of the cases where MET-PET/CT was performed after inconclusive or contradicting US and/or SuSc, MET-PET/CT had an additional value in localization of the adenoma. Conclusion: MET-PET/CT seems a valuable imaging modality in hyperparathyroidism with a higher per-lesion sensitivity than US. Especially when US and/or SuSc are inconclusive or negative, MET-PET/CT directs the surgeon to the correct localization of the adenoma.

54. Risk of Malignancy of the Thyroid Nodule Evaluated by Scintigraphy

Author

Bravenboer Bert, Keyaerts Marleen, Andreescu Corina, De Meyst Elias, Raeymaeckers Steven, Velkeniers Brigitte, Faculty of Medicine and Pharmacy, Gerontology, Geriatrics, Internal Medicine, Supporting clinical sciences, Medical Imaging, Nuclear Medicine, Basic (bio-) Medical Sciences, Radiology, and Clinical sciences

Subjects
medicine.medical_specialty, medicine.anatomical_structure, medicine.diagnostic_test, business.industry, Risk of malignancy, Thyroid, medicine, Nodule (medicine), Radiology, medicine.symptom, business, Scintigraphy
Abstract

Background: Thyroid nodules are a common finding in clinical practice. Among classic risk factors for thyroid cancer, thyroid scintigraphy has traditionally been attributed prognostic value, with cold nodules implying greater risk. However, research supporting this assumption is of considerable age and possibly influenced by selection bias. In this study, we aimed to calculate the risk of malignancy in cold and hot nodules. Material and Methods: All thyroid nodules that underwent both thyroid scintigraphy and pathologic characterisation (cytology and/or histology) in a 5-year period at a tertiary centre were retrospectively analysed. Cancer rates were calculated in cold and hot nodules. Furthermore, rates of malignancy were calculated taking into account several established and more controversial risk factors for thyroid carcinoma, in order to identify subgroups with greater risk for cancer. Results: 343 thyroid nodules were included for study. Cancer rates were 7.7% in cold nodules (N=248) and 5.3% in hot nodules (N=95). Thyrotropin levels were lower in hot nodules (P=0.000), and levels were higher in cancerous cold nodules compared with benign cold nodules (P=0.014). A cancer rate of 26.7% was noted in cold nodules with elevated anti-thyroglobulin levels. In all other subgroup analyses, the rate of malignancy in cold nodules was never higher than cancer rates suggested by literature for nodules in the general population. Although similar observations were made for hot nodules, no definite conclusions were drawn as there were too few hot nodules to perform statistical tests. Conclusion: Our findings suggest that cold nodules are not high-risk nodules by definition, as their cancer rates were not notably higher than the risk of malignancy proposed in literature for nodules in the general population. Therefore, we discourage the use of thyroid scintigraphy for the selection of cold nodules for further pathologic characterisation.

55. Rare Thyroid Diseases Mimicking or Concealing Primitive Thyroid Neoplasms: A Call for a "Check and Double-Check" Clinical Mindset.

Author

Duhamel F, Balti E, Waelput W, Raeymaeckers S, Verfaillie G, Luyten I, and Andreescu CE

Abstract

Clinical endocrinologists encounter in their practice patients with thyroid diseases on a daily basis. Still, diagnosis of rare structural thyroid disorders can be quite challenging. In some instances, they do not only impersonate but can also conceal, other conditions such as thyroid carcinomas. We describe a series of patients with structural thyroid disorders including 1) anaplastic thyroid carcinoma initially presenting with features of thyroid abscess; 2) unicentric hyaline vascular Castleman's disease of the thyroid embedded in a stroma of papillary thyroid carcinoma; and 3) primary thyroid lymphoma with a rapid and fulminant evolution. The common challenge in the diagnosis of these cases lies in both their low incidence and their complex presentation. We use the presentation of these cases to raise the attention related to their identification. We highlight the need for precision diagnosis to enable a patient-tailored management approach and improve patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Duhamel et al.)

Published
2024
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56. Intratumoral administration of the immunologic adjuvant AS01 B in combination with autologous CD1c (BDCA-1) + /CD141 (BDCA-3) + myeloid dendritic cells plus ipilimumab and intravenous nivolumab in patients with refractory advanced melanoma.

Author

Tijtgat J, Geeraerts X, Boisson A, Stevens L, Vounckx M, Dirven I, Schwarze JK, Raeymaeckers S, Forsyth R, Van Riet I, Tuyaerts S, Willard-Gallo K, and Neyns B

Subjects
Humans, Nivolumab adverse effects, Ipilimumab pharmacology, Ipilimumab therapeutic use, Adjuvants, Immunologic adverse effects, Proto-Oncogene Proteins B-raf, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Administration, Intravenous, Mitogen-Activated Protein Kinase Kinases, Tumor Microenvironment, Melanoma pathology
Abstract

Background: Patients with advanced melanoma who progress after treatment with immune checkpoint-inhibitors (ICI) and BRAF-/MEK-inhibitors (if BRAF V600 mutated) have no remaining effective treatment options. The presence of CD1c (BDCA-1) + and CD141 (BDCA-3) + myeloid dendritic cells (myDC) in the tumor microenvironment correlates with pre-existing immune recognition and responsiveness to immune checkpoint blockade. The synthetic saponin-based immune adjuvant AS01 B enhances adaptive immunity through the involvement of myDC., Methods: In this first-in-human phase I clinical trial, patients with metastatic melanoma refractory to ICI and BRAF-/MEK inhibitors (when indicated) were recruited. Patients received an intravenous administration of low-dose nivolumab (10 mg, every 2 weeks) plus an intratumoral (IT) administration of 10 mg ipilimumab and 50 µg (0.5 mL) AS01 B (every 2 weeks). All myDC, isolated from blood, were injected on day 2 into the same metastatic lesion. Tumor biopsies and blood samples were collected at baseline and repeatedly on treatment. Multiplex immunohistochemistry (mIHC) was performed on biopsy sections to characterize and quantify the IT and peritumoral immune cell composition., Results: Study treatment was feasible and well tolerated without the occurrence of unexpected adverse events in all eight patients. Four patients (50%) obtained a complete response (CR) in the injected lesions. Of these, two patients obtained an overall CR, and one patient a partial response. All responses are ongoing after more than 1 year of follow-up. One additional patient had a stable disease as best response. The disease control rate was 50%. Median progression-free survival and overall survival were 24.1 and 41.9 weeks, respectively. Baseline tumor biopsies from patients who responded to treatment had features of T-cell exclusion. During treatment, there was an increased T-cell infiltration, with a reduced mean distance between T cells and tumor cells. Peripheral blood immune cell composition did not significantly change during study treatment., Conclusions: Combining an intratumoral injection of CD1c (BDCA-1) + and CD141 (BDCA-3) + myDC with repeated IT administration of ipilimumab and AS01 B and systemic low-dose nivolumab is safe, feasible with promising early results, worthy of further clinical investigation., Trial Registration Number: ClinicalTrials.gov identifier NCT03707808., Competing Interests: Competing interests: JT reports participation in Novartis junior advisory board meeting. JKS reports non-financial support from MSD and Amgen; personal fees from Novartis. BN reports personal financial compensation from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, AstraZeneca for public speaking, consultancy and participation in advisory board meetings. The institution (UZ Brussel) received research funding related to research projects conducted by Bart Neyns from Pfizer, Novartis, Roche, Merck-Serono. The other authors do not declare any competing interests., (© 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.)

Published
2024
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57. [A patient with high creatinine levels but no renal failure: reversed autodialysis in a patient with a ruptured bladder].

Author

Raeymaeckers S, Tosi M, Van Bael K, Brussaard C, and De Mey J

Subjects
Abdominal Pain diagnosis, Abdominal Pain etiology, Acute Kidney Injury diagnosis, Adult, Diagnosis, Differential, Female, Humans, Postoperative Complications, Rupture, Urinary Bladder surgery, Creatinine blood, Urea blood, Urinary Bladder injuries
Abstract

Background: In case of a ruptured bladder with urine leakage into the peritoneal cavity 'reversed autodialysis' can occur, in which urea and creatinine diffuse back into the bloodstream via the peritoneum. This causes clinical signs of pseudorenal failure, with raised concentrations of creatinine and urea. The urea/creatinine ratio does not change., Case Description: A 34-year-old female patient experienced increasing abdominal pain 3 days after laparoscopic myomectomy. Acute renal failure was suspected because of increased serum concentrations of creatinine and urea, but no cause could be found. There was a build-up of fluid in the abdominal cavity, which proved to be urine originating from an iatrogenic rupture of the bladder. Serum levels normalised following repair of the rupture., Conclusion: If serum creatinine levels rise rapidly following abdominal surgery or blunt abdominal trauma the bladder should be examined for possible perforation, particularly if the abdominal dimension increases. A ruptured bladder leading to pseudorenal failure is an indication for rapid surgical intervention.

Published
2016

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