Background It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS).... Show moreBackground It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS). However, the effects of ageing on aortic hemodynamics have not yet been described. Case summary 4D-Flow MRI derived aorta hemodynamics were derived in the ascending aorta of a patient with ascending aortic aneurysm (mean +/- standard deviation: 46 +/- 1 mm) and a healthy volunteer (aortic diameter 30 +/- 1 mm) with long-term follow-up of ten and eight years, respectively. At all timepoints, compared to the healthy volunteer, the patient demonstrated higher magnitudes of FDN (7% +/- 1% vs. 3% +/- 1%) and WSS angle (36 degrees +/- 3 degrees vs. 24 degrees +/- 6 degrees), and lower WSS magnitude (565 +/- 100 mPa vs. 910 +/- 115 mPa), axial WSS (426 +/- 71 mPa vs. 800 +/- 108 mPa) and circumferential WSS (297 +/- 64 mPa vs. 340 +/- 85 mPa). The patient and healthy volunteer demonstrated different aortic dilatation rates (regression slope +/- standard error: 0.2 +/- 0.1 vs. 0.1 +/- 0.2 mm per year) and trends in FDN (0.1% +/- 0.1% vs. 0.1% +/- 0.2% per year), WSS magnitude (22 +/- 9 vs. 35 +/- 13 mPa per year), axial WSS (19 +/- 4 vs. 37 +/- 7 mPa per year), circumferential WSS (9 +/- 8 vs. 5 +/- 15 mPa per year), and WSS angle (-0.5 degrees +/- 0.4 degrees vs. -0.8 degrees +/- 1.0 degrees per year). Discussion Aortic hemodynamic parameters are marginally affected by ageing and the aortic diameter in this case series. Since aortic hemodynamic parameters have been associated with aortic dilation by previous studies, the outcomes of the two subjects suggest that the aortic dilatation rate will remain constant while individuals are ageing and dilating. Show less
Henegouwen, J.M.V.; Wijngaart, H. van der; Zeverijn, L.J.; Hoes, L.R.; Meertens, M.; Huitema, A.D.R.; ... ; Gelderblom, H. 2022
Introduction The combination of vemurafenib, a proto-oncogene B-Raf inhibitor (BRAFi) and cobimetinib, an inhibitor of mitogen-activated protein kinase kinase (MEKi) has shown to improve survival... Show moreIntroduction The combination of vemurafenib, a proto-oncogene B-Raf inhibitor (BRAFi) and cobimetinib, an inhibitor of mitogen-activated protein kinase kinase (MEKi) has shown to improve survival in patients with BRAF V600-mutated melanoma. BRAF mutations are also frequently detected driver mutations in other tumor types, including thyroid carcinoma. Since thyroid carcinoma is not a labeled indication for BRAF/MEKi, a cohort for patients with BRAF V600-mutated thyroid carcinoma was opened within the Drug Rediscovery Protocol (DRUP), a national ongoing pan-cancer multi-drug trial, in which patients receive off-label treatment with approved drugs based on their molecular tumor profile. Results Here, we present two patients with BRAF-mutated thyroid carcinoma, who were successfully treated with vemurafenib/cobimetinib administered via a feeding tube. Plasma concentrations of vemurafenib and cobimetinib were determined. A partial response was observed in both patients, but they experienced significant toxicity. Conclusion Our cases show that vemurafenib/cobimetinib treatment is effective in BRAF V600-mutated thyroid carcinoma, also when administered via a feeding tube. Although serious side effects occurred in both patients, we hypothesize that this was not attributable to the administration route. Therefore, administration of vemurafenib/cobimetinib by feeding tube is feasible and effective. Show less
Background Cardiotoxicity presenting as cardiomyopathy is a common side effect in cancer treatment especially with anthracyclines. The role of genetic predisposition is still being investigated... Show moreBackground Cardiotoxicity presenting as cardiomyopathy is a common side effect in cancer treatment especially with anthracyclines. The role of genetic predisposition is still being investigated.Case summary Four unrelated patients with a familial burden for cardiac disease, who developed cardiomyopathy after anthracycline treatment are presented. Case 1 received chemotherapy for breast cancer and developed a dilated left ventricle just after treatment. Her father had died unexpectedly while being screened for heart transplant. Case 2 was known with a family history of sudden cardiac death prior to her breast cancer diagnosis. She received anthracycline-containing chemotherapy treatment twice in 5 years due to recurrence of breast cancer. During that period, two brothers developed a cardiomyopathy. Eighteen years later, a genetic predisposition for cardiomyopathy was ascertained and at screening an asymptomatic non-ischaemic cardiomyopathy was established. Case 3 was diagnosed with a dilated cardiomyopathy 1 year after chemotherapy treatment for breast cancer. Her mother had developed a dilated cardiomyopathy several years before. Case 4 received chemotherapy treatment for Non-Hodgkin's lymphoma and developed dilated cardiomyopathy 1 year later. His brother died from congestive heart failure which he developed after chemotherapy for Non-Hodgkin's lymphoma and a grandmother had died suddenly during child delivery. In all four cases, genetic screening showed (likely) pathogenic variants in cardiomyopathy-associated genes.Discussion Current guidelines recommend cardiac evaluation in cancer patients receiving chemotherapy based on the presence of cardiovascular risk factors at the start of treatment. This series emphasizes the importance of including a thorough family history in this process. Show less
