Publications by authors named "Frank Hammer"

34 Publications

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

JAMA Cardiol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear.

Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls.

Design, Setting, And Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA.

Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).

Main Outcome And Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index).

Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events.

Conclusions And Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.
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http://dx.doi.org/10.1001/jamacardio.2021.4690DOI Listing
November 2021

Peripheral embolism as first and only clinical symptom of a true aneurysmal degeneration of the radial artery after ligation of a radiocephalic fistula.

J Vasc Access 2021 Jul 29:11297298211033383. Epub 2021 Jul 29.

Surgery and Abdominal Transplant Unit, Department of Surgery, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

True aneurysmal degeneration of the inflow artery after arteriovenous fistula ligation is extremely rare. Pain is the most common symptom and surgical treatment by an autologous venous bypass is considered as the treatment of choice with good long-term results. We present a patient with peripheral embolism as first and only symptom leading to the diagnosis of a true aneurysmal degeneration of the entire left radial artery. It was discovered 5 years after the ligation of his radiocephalic fistula. As illustrated by this case, a conservative treatment by antiplatelet and anticoagulation therapy should be considered a satisfying alternative to the standard bypass surgery in patients with anatomical variations (e.g. an incomplete arterial palmar arch) since the latter include a higher risk of postoperative ischemic complications.
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http://dx.doi.org/10.1177/11297298211033383DOI Listing
July 2021

Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations.

Orphanet J Rare Dis 2021 06 10;16(1):267. Epub 2021 Jun 10.

Human Molecular Genetics, de Duve Institute, University of Louvain, Avenue Hippocrate 74 (+5), bte B1.74.06, 1200, Brussels, Belgium.

Background: Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients' genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)].

Results: We identified a somatic PIK3CA mutation in resected lesions of 108 out of 143 patients (75.5%). The frequency of the variant allele ranged from 0.54 to 25.33% in tissues, and up to 47% in isolated endothelial cells. We detected a statistically significant difference in the distribution of mutations between patients with common and combined LM compared to the syndromes, but not with KTS. Moreover, the variant allele frequency was higher in the syndromes.

Conclusions: Most patients with an common or combined lymphatic malformation with or without overgrowth harbour a somatic PIK3CA mutation. However, in about a quarter of patients, no such mutation was detected, suggesting the existence of (an)other cause(s). We detected a hotspot mutation more frequently in common and combined LMs compared to syndromic cases (CLOVES and PROS). Diagnostic genotyping should thus not be limited to PIK3CA hotspot mutations. Moreover, the higher mutant allele frequency in syndromes suggests a wider distribution in patients' tissues, facilitating detection. Clinical trials have demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. Genotyping might lead to an increase in efficacy, as treatments could be more targeted, and responses could vary depending on presence and type of PIK3CA-mutation.
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http://dx.doi.org/10.1186/s13023-021-01898-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194016PMC
June 2021

Prevalence, Characteristics, and Prognosis of Peripheral Arterial Disease in Patients With Diabetic Charcot Foot.

J Foot Ankle Surg 2021 Nov-Dec;60(6):1158-1163. Epub 2021 May 8.

Attending Physician, Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Charcot foot (CF) is a rare complication of diabetes associated with foot deformities and foot ulcers. Peripheral arterial disease (PAD) is a factor of poor prognosis in patients with diabetic foot ulcers (DFUs). However, PAD has infrequently been studied in CF. We aimed to determine the prevalence, the characteristics and the prognosis of PAD in a large group of patients with diabetic CF. We retrospectively compared 56 patients with diabetic CF to 116 patients with diabetic foot without CF. The prevalence of PAD in patients with CF was 66.1%. Compared to patients without CF, patients with CF had similar risks to have PAD (OR 0.98, 95%CI 0.50-1.94, p= .97) and neuro-ischemic DFUs (OR 1.19, 95%CI 0.57-2.49, p= .65), more risk to have lesions of distal arteries (OR 4.17, 95%CI 1.76-9.94, p= .001) and less risk to need revascularization (OR 0.14, 95%CI 0.06-0.36, p< .001). In patients with CF, PAD was strongly predicted by DFUs (OR 24.55, 95%CI 1.80-334.43, p= .016) and coronary artery disease (OR 17.11, 95%CI 1.75-167.43, p =.015). Survival rate and limb salvage rate in patients with CF were not worsened by PAD and by neuro-ischemic DFUs, respectively. In conclusion, we show that PAD should not be overlooked in patients with diabetic CF, especially in those having DFUs or coronary artery disease. PAD in patients with CF differed from that of patients without CF since it predominated in distal arteries and required less often revascularization.
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http://dx.doi.org/10.1053/j.jfas.2021.04.021DOI Listing
November 2021

Low rate of subclinical venous thrombosis in patients with haemophilia undergoing major orthopaedic surgery in the absence of pharmacological thromboprophylaxis.

Haemophilia 2020 Nov;26(6):1064-1071

Hemostasis and Thrombosis Unit, Division of Hematology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium.

Background: Deep venous thrombosis (DVT) is a common postoperative complication in patients undergoing major orthopaedic surgery of the lower limbs, such as total hip or knee replacement (THR, TKR). Routine pharmacological thromboprophylaxis with low-molecular-weight heparin (LMWH) or a direct oral anticoagulant agent is strongly recommended in this setting. THR and TKR as well as ankle arthrodesis are frequently performed in people with haemophilia (PWH) and chronic haemophilic arthropathy. Pharmacological thromboprophylaxis in this population remains controversial.

Methods: We report the results of a single-centre prospective study initiated in 2002 evaluating by systematic Doppler ultrasound the incidence of subclinical DVT in consecutive PWH referred for major orthopaedic surgery and not receiving pharmacological thromboprophylaxis.

Results: We included 46 different PWH (39 Haemophilia A, 7 Haemophilia B, 27 severe, 15 moderate and 4 mild forms) undergoing 67 orthopaedic procedures. Most (89.5%) were performed with continuous infusion of clotting factor concentrates. Rehabilitation was usually started on day 1 post-op. No clinical DVT or pulmonary embolism was suspected. In total, there were 5 cases (3 severe, 1 moderate HA and 1 moderate HB) of subclinical DVT which were all distal. Two patients were treated with a short course (10-14 days) of LMWH. The overall incidence of DVT was 7.5%.

Conclusions: These data provide imaging-based evidence that the risk of DVT following major orthopaedic surgery among PWH is low. Identified DVTs were distal and resolved spontaneously in most cases. Systematic pharmacological thromboprophylaxis in this specific population is probably for most patients not required.
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http://dx.doi.org/10.1111/hae.14161DOI Listing
November 2020

Experience With Medical Treatment of Cesarean Scar Ectopic Pregnancy (CSEP) With Local Ultrasound-Guided Injection of Methotrexate.

Front Med (Lausanne) 2020 3;7:564764. Epub 2020 Nov 3.

Department of Gynaecology and Andrology, Cliniques Universitaires Saint Luc, Woluwe-Saint-Lambert, Belgium.

Ectopic pregnancy within Cesarean section scars is a rare condition. Late diagnosis carries significant risk of bleeding with poor prognosis for survival. There is no consensus on the management of this type of pregnancy. Historically, our facility offered an intra-muscular injection of methotrexate that resulted in a significant failure rate and later need for surgery. We hypothesized that injecting methotrexate directly into the gestational sac would improve the success rate of the treatment. This retrospective, uni-centric study examined nine patients aged between 33 and 42 years (mean age = 36.5 years) with Cesarean scar ectopic pregnancy (CSEP) between 2010 and 2018. CSEP was diagnosed by transvaginal ultrasound at a mean gestational age of 8w0/7. CSEP was treated under general anesthetic by ultrasound-guided methotrexate injection directly into the gestational sac. HCG levels and subsequent childbearing were monitored post-treatment. Half of the patients were asymptomatic at the time of diagnosis. All patients tolerated treatment well and all ectopic pregnancies were successfully removed. HCG levels returned to negative within 3 months without additional medical or surgical intervention. The post-treatment pregnancy rate was 50%. Our findings indicate that local ultrasound-guided injection of methotrexate into the gestational sac is a safe and effective therapeutic approach when performed by a trained team on a hemodynamically stable patient in the early stages of CSEP.
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http://dx.doi.org/10.3389/fmed.2020.564764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671087PMC
November 2020

Multicenter, retrospective analysis of endovascular treatment for acute ischemic stroke in nonagenarians.

J Stroke Cerebrovasc Dis 2020 Aug 25;29(8):104817. Epub 2020 Apr 25.

Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Antwerp University Hospital, Edegem, Belgium; AZ Groeninge Kortrijk, Antwerp University Hospital and University Antwerp, Antwerpen, Belgium.

Background: With the increasing age of acute stroke patients being admitted to hospitals, more data are needed on indications, complications and outcome of endovascular treatment (EVT) in the very elderly.

Methods: Retrospective observational study with data collection from Belgian, Swiss, Canadian comprehensive stroke centers and Swedish EVT National database. All patients with acute ischemic stroke were eligible if aged older than or ≥90 years and treated with EVT ± pretreatment with intravenous thrombolysis (IVT). Safety assessment comprised presence of periprocedural complications, hemorrhagic transformation or other adverse events (<7days). Efficacy and outcome measures were successful recanalization (modified Treatment In Cerebral Infarction (mTICI) score ≥2b), favorable clinical outcome (modified Rankin Score (mRS) 0-2) and 3-months mortality.

Results: Inclusion of 112 nonagenarians (mean age 93.3 ± 2.5 years; 76.8% women; pre-mRS ≤2 in 69.4%). Pretreatment with IVT was performed in 54.7%. In 74.6% successful recanalization (mTICI ≥2b) was achieved. Favorable outcome (mRS ≤2) was seen in 16.4% and 3-months mortality was 62.3%. Multivariate logistic regression analysis showed younger age (odds ratio [OR] 2.99; 1.29-6.95; P = .011) and lower prestroke mRS (OR 13.46; 2.32-78.30; P = .004) as significant predictors for good clinical outcome at 90 days.

Conclusions: Our observational study on EVT in nonagenarians demonstrates the need for careful patient selection. A substantial proportion of nonagenarians shows an unfavorable clinical outcome and high mortality, despite acceptable recanalization rates. A high prestroke disability (mRS) and advancing age predict an unfavorable outcome. Treatment decisions should be made on case-by-case evaluation, keeping in mind limited chances of favorable outcome and high risk of mortality.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104817DOI Listing
August 2020

Acute stroke care during the COVID-19 pandemic: difficult, but not impossible!

Acta Neurol Belg 2020 10 7;120(5):1257-1258. Epub 2020 Jul 7.

Department of Neurology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium.

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http://dx.doi.org/10.1007/s13760-020-01422-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338338PMC
October 2020

Prevalence and characteristics of renal artery fibromuscular dysplasia in hypertensive women below 50 years old.

Eur J Clin Invest 2019 Oct 19;49(10):e13166. Epub 2019 Sep 19.

Division of Cardiology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

Background: Renal fibromuscular dysplasia (FMD) is typically diagnosed in young hypertensive women. The 2014 European FMD Consensus recommended screening in all hypertensive women <30 yo. However, the prevalence of renal FMD in young/middle-aged hypertensive women remains unclear. The aim of this work was to assess the prevalence and characteristics of renal FMD in hypertensive women ≤50 yo.

Methods: We retrospectively included all consecutive women aged ≤50 years referred to our Hypertension Unit from 2014 to 2017 and collected standardized information on patient characteristics and screening modalities.

Results: Of 1083 incident hypertensive patients, 157 patients fitted with inclusion criteria. The prevalence of renal FMD varied between 3.2% in the whole sample and 7.5% in patients explored by CTA and/or MRA (n = 67). In the subgroup of patients ≤30 yo (n = 32), the corresponding figures were 3.1% and 5.6%. The yearly prevalence of FMD tended to increase over time, in parallel with increased use of CTA/MRA as a first-line imaging modality. Out of 5 patients with renal FMD, 2 were revascularized and 1 had extra-renal FMD.

Conclusions: The prevalence of renal FMD in young/middle-aged hypertensive women is probably one order of magnitude higher than previously assumed, in the range of 3%-8%, depending on imaging modalities. While the diagnosis of FMD does not influence short-term management in all patients, it may allow close monitoring and prevention of complications of the disease over time. This analysis provides the rationale for a prospective, multicentre study aiming at determining the cost-effectiveness of systematic screening for renal FMD.
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http://dx.doi.org/10.1111/eci.13166DOI Listing
October 2019

Cervical artery dissection: fibromuscular dysplasia versus vascular Ehlers-Danlos syndrome.

Blood Press 2019 04 9;28(2):139-143. Epub 2019 Jan 9.

a Division of Cardiology , Cliniques Universitaires Saint-Luc, Université Catholique de Louvain , Brussels , Belgium.

We report the case of a 42-year-old patient referred for suspicion of fibromuscular dysplasia in the context of a carotid artery dissection occurring after a minor trauma. Initial complaints included left hemicrania, lateral diplopia with left 6 cranial nerve palsy and pulsatile tinnitus. The work-up disclosed a large left carotid-cavernous fistula, as well as more proximal carotid lesions compatible with multifocal fibromuscular dysplasia. Personal history included colonic and uterine perforation. Family history disclosed a fatal hemorrhage due to rupture of a splenic artery aneurysm in the father and an iliac dissection in the sister. Genetic screening revealed a mutation in exon 6 of the COL3A1 gene in the index patient and her sister, confirming the diagnosis of vascular Ehlers-Danlos syndrome (vEDS). This case report shows that images suggestive of fibromuscular dysplasia may be found in patients with demonstrated vEDS. Furthermore, it reminds that in case of cervical artery dissection occurring in a young patient, all efforts should be made to diagnose the underlying condition. In particular, the existence of a family history of arterial dissection, the occurrence of a carotid-cavernous fistula and coexistence with other complications suggestive of a connective tissue disease should prompt physicians to consider the diagnosis of vEDS.
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http://dx.doi.org/10.1080/08037051.2018.1557507DOI Listing
April 2019

Sirolimus is efficacious in treatment for extensive and/or complex slow-flow vascular malformations: a monocentric prospective phase II study.

Orphanet J Rare Dis 2018 10 29;13(1):191. Epub 2018 Oct 29.

Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires Saint Luc, University of Louvain, 10 avenue Hippocrate, B-1200, Brussels, Belgium.

Background: Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. The purpose of this prospective study was to assess the efficacy and safety of this treatment in patients with extensive or complex slow-flow vascular malformations.

Methods: Sirolimus was administered orally on a continuous dosing schedule with pharmacokinetic-guided target serum concentration level of 10 to 15 ng/ml. Patients were seen every month for the first three months and subsequently every three months. The primary endpoints were safety and efficacy, based on clinical, biological and radiological evaluations, as well as a quality of life questionnaire.

Results: Nineteen patients, from 3 to 64 years old, with lymphatic (LM), venous (VM) or complex slow-flow malformations, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, 16 patients were available for assessment of efficacy and safety: all had a significant and rapid improvement of their symptoms and quality of life. In two patients, sirolimus treatment permitted sclerotherapy and surgery, initially evaluated unfeasible. Sirolimus was well tolerated, with mucositis as the most common (10% of patients) grade 3 adverse event.

Conclusions: Sirolimus was efficient in extensive LM, VM and/or complex malformations that were refractory to conventional treatments and was well tolerated.
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http://dx.doi.org/10.1186/s13023-018-0934-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206885PMC
October 2018

A Proposed Simple and Accurate Technique for Optimal Long-Term Hemodialysis Catheter Tip Placement.

J Belg Soc Radiol 2018 Jan 31;102(1):21. Epub 2018 Jan 31.

Cliniques univeristaires Saint-Luc, BE.

We describe a simple ultrasound (US)-guided technique for accurate anatomical right atrium localization prior to permanent hemodialysis catheter insertion. It is used in patients for whom a permanent hemodialysis catheter will be inserted through an internal jugular vein access, in order to have the functional catheter tip located at the mid-level of the right atrium. In this technique, the right atrium is localized on US via left intercostal approach prior to catheter insertion under fluoroscopic guidance.
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http://dx.doi.org/10.5334/jbsr.1474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032382PMC
January 2018

Superior vena cava stenosis in haemodialysis patients with a tunnelled cuffed catheter: prevalence and risk factors.

Nephrol Dial Transplant 2018 12;33(12):2227-2233

Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

Background: Although superior vena cava (SVC) stenosis may be a life-threatening complication of haemodialysis (HD) catheters, its prevalence and risk factors in HD patients are unknown. Our aim was to assess the prevalence and risk factors for SVC stenosis in HD patients with a tunnelled cuffed catheter (TCC) and to describe its clinical presentation.

Methods: In this single-centre, retrospective cohort study, all in-centre chronic HD patients carrying a TCC (1 January 2008-31 December 2012) were included (n = 117 patients, 214 TCC, 80 911 catheter-days). SVC stenosis was defined as a diameter reduction >50% on phlebography or computed tomography. Imaging was triggered by clinical SVC stenosis syndrome or vascular access (VA)-related concerns. We recorded demographics, conditions potentially influencing catheter permeability (medications, carriage of thoracic devices), number of TCCs, total duration of TCC carriage, previous arteriovenous VA and last (in use at time of stenosis detection) TCC details (location, diameter and length). VAs created while a TCC was still used were also recorded.

Results: An SVC stenosis was found in 11 patients (9.4%, 0.14/1000 catheter-days), which represents almost one-quarter of patients undergoing imaging, whatever the cause (11/45). Only two presented with clinically obvious SVC stenosis. The number of TCCs per patient was 2.64 ± 1.8 in the SVC stenosis group versus 1.75 ± 0.94 in the negative group (P = 0.13). On multivariate analysis (Poisson), diabetes {incidence rate ratio [IRR] 4.63 [confidence interval (CI) 1.2-17.8]; P = 0.02} and total duration of TCC carriage [IRR 1.47 (CI 1.2-1.8) per year; P = 0.001] were associated with SVC stenosis, whereas age had a slightly protective effect [IRR 0.96 (CI 0.91-1.01); P = 0.01]. Limitations are the retrospective design, detection and survivor bias.

Conclusion: SVC stenosis is not a rare condition, is mostly asymptomatic in the absence of a peripheral VA, is strongly associated with diabetes and is promoted by long TCC carriage. Age is slightly protective.
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http://dx.doi.org/10.1093/ndt/gfy150DOI Listing
December 2018

Systemic thrombolysis and endovascular thrombectomy in severe acute ischemic stroke after dabigatran reversal with idarucizumab.

Clin Case Rep 2018 04 27;6(4):698-701. Epub 2018 Feb 27.

Hemostasis and Thrombosis Unit Division of Adult Hematology Cliniques Universitaires Saint-Luc Brussels 1200 Belgium.

Patients presenting with an acute ischemic stroke despite dabigatran therapy (last intake <24 h or unknown) should be evaluated for reversal by idarucizumab, making them eligible for safe and effective intravenous thrombolysis. It has been shown to be feasible, well-tolerated, and easy to manage in an emergency room or stroke unit.
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http://dx.doi.org/10.1002/ccr3.1446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889252PMC
April 2018

Management of a Pregnant Woman With Fibromuscular Dysplasia.

Hypertension 2018 04 26;71(4):540-547. Epub 2018 Feb 26.

From the Department of Cardiology, Cliniques Universitaires Saint-Luc (E.B., S.P., A.P.), Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (S.P., A.P.), and Department of Radiology, Cliniques Universitaires Saint-Luc (F.H.), Université Catholique de Louvain, Brussels, Belgium; Internal Medicine and Hypertension Division, Department of Medical Sciences, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom (A.F.D., R.M.T.); Division of Internal Medicine and Hypertension Unit, Department of Medical Science, University of Padova, Italy (G.P.R.); Department of Hypertension, Hospital Italiano de Buenos Aires, Argentina (R.G.M.); Department of Hypertension, Instituto Cardiovascular Lezica, San Isidro, Argentina (R.G.M.); Abbott Argentina, Buenos Aires (R.G.M.); Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (J.A.S.); Hadassah-Hebrew University Medical Center, Mount-Scopus, Jerusalem, Israel (M.B.); and Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (T.K.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.10819DOI Listing
April 2018

High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular Dysplasia: The ARCADIA Registry (Assessment of Renal and Cervical Artery Dysplasia).

Hypertension 2017 09 17;70(3):652-658. Epub 2017 Jul 17.

Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B., O.O.), Department of Radiology (F.T.), and INSERM U1039 (J.-P.B.), France; Hypertension Unit, CHU Timone, Marseille, France (F.S.); Department of Radiology, CHU Gabriel-Montpied, Clermont-Ferrand, France (L.B.); Hypertension Unit, CHU Rangueil, Toulouse, France (B.B.); Hypertension Unit, Hôpital Cardiologique, Lille, France (C.M.-V.); Normandie Université, University of Caen Normandy, INSERM U919, CHU de Caen, Unité Neurovasculaire, France (E.T.); Department of Vascular Medicine (C.L.H.), Caen, France; Hôpital Saint André, Bordeaux, France (P.G.); Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P.); Division of Cardiology (A.P.) and Division of Radiology (F.H.), Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associated with multisite FMD (string-of-beds or focal stenoses affecting at least 2 vascular beds) are not known. In the prospective ARCADIA registry (Assessment of Renal and Cervical Artery Dysplasia), symptomatic patients with renal artery (RA) FMD underwent tomographic- or magnetic resonance-angiography from the aortic arch to the intracranial arteries and those with cervical FMD from the diaphragm to the pelvis. Of 469 patients (84.0% women), 225 (48.0%) had multisite FMD. In addition, 86 of 244 patients with single-site disease had dissections or aneurisms affecting other vascular beds, totaling 311 patients (66.3%) with lesions in >1 vascular bed. Among patients with a cerebrovascular presentation, the prevalence of RA lesions was higher in patients with than in those without hypertension (odds ratio, 3.4; 95% confidence interval, 1.99-6.15). Among patients with a renal presentation, the prevalence of cervical lesions was higher in patients with bilateral than in those with unilateral RA lesions (odds ratio, 1.9; 95% confidence interval, 0.99-3.57). In conclusion, FMD is a systemic arterial disease. At least 2 vascular beds were affected by dysplastic stenoses in 48.0% of cases and by dysplastic stenoses, aneurysms, and dissections in 66.1% of cases. RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation. Cervical artery imaging should be considered in patients with a renal presentation and bilateral RA lesions.

Clinical Trial Registration: URL: www.Clinicaltrials.gov. Unique identifier: NCT02884141.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09539DOI Listing
September 2017

Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension.

Blood Press 2017 12 10;26(6):321-331. Epub 2017 May 10.

a Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences , University of Leuven , Leuven , Belgium.

Objective: Previous trials of catheter-based renal-artery denervation (RDN) as treatment modality in resistant hypertension (rHT) generated unconvincing results. In the Investigator-Steered Project on Intravascular Denervation for Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we optimized selection and management of rHT patients.

Methods: With ethical clearance to randomize 18 patients, three Belgian hypertension centers screened 29 rHT patients on treatment with ≥3 drugs, of whom 17 after optimization of treatment (age <70 years; systolic/diastolic office blood pressure (BP) ≥ 140/90 mm Hg; 24-h BP ≥130/80 mm Hg; glomerular filtration rate [eGFR] ≥ 45 mL/min/1.73 m; body mass index <40kg/m) were randomized and 15 were analyzed 6 months later, while medical treatment was continued (n = 9) or combined with RDN by the EnligHTN™ multi-electrode system (n = 6).

Results: The baseline-adjusted between-group differences amounted to 19.5/10.4 mm Hg (change in control vs. intervention group, +7.6/+2.2 vs. -11.9/-8.2 mm Hg; P = .088) for office BP, 22.4/13.1 mm Hg (+0.7/+0.3 vs. -21.7/-12.8; mm Hg; P ≤ .049) for 24-h BP, the primary efficacy endpoint, and 2.5 mL/min/1.73 m (+1.5 vs. -1.1 mL/min/1.73 m; P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the number of prescribed drugs (P ≤ .036) were lower in RDN patients, but quality of life and adherence, captured by questionnaire and urine analysis were similar in both groups. Changes in BP and adherence were unrelated. No major complications occurred.

Conclusions: The INSPiRED pilot suggests that RDN with the EnligHTN system is effective and safe and generated insights useful for the design of future RDN trials.
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http://dx.doi.org/10.1080/08037051.2017.1320939DOI Listing
December 2017

Intraparenchymal Renal Artery Pseudoaneurysm and Arteriovenous Fistula on a Solitary Kidney Occurring 38 Years after Blunt Trauma.

Case Rep Urol 2017 13;2017:3017501. Epub 2017 Mar 13.

Department of Urology, University Clinics Saint Luc, Catholic University of Louvain, 10 Avenue Hippocrate, 1200 Brussels, Belgium.

Pseudoaneurysm and arteriovenous fistulae of the renal artery are rare complications of kidney trauma. They commonly result from open traumas and occur within days after the injury. Common symptoms include acute haematuria, pain, or hypertension. We report the case of a fifty-three-year-old man presenting with symptomatic complex chronic high flow kidney arteriovenous fistula with interposition of a pseudoaneurysmal pouch and arterial aneurysmal dilatation in a solitary left kidney 38 years after a blunt trauma. Those conditions were successfully treated by endovascular embolization followed by regular radiologic, biological, and clinical follow-up. To the best of our knowledge, few similar cases were reported more than 20 years after trauma. However, no case combining an arteriovenous fistula and a pseudoaneurysm revealing as late as 38 years after trauma was found. In addition, management of those conditions on a solitary kidney and outcomes has not been described. We believe that our case depicts the clinical presentation and management of this rare entity that should not be unrecognized due to its potential lethal implications.
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http://dx.doi.org/10.1155/2017/3017501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366758PMC
March 2017

Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography.

Eur Radiol 2017 Sep 7;27(9):3934-3941. Epub 2017 Mar 7.

Department of Nephrology and Hypertension, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.

Objectives: Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated.

Methods: This study is an initiative of ENCOReD, a collaboration of hypertension expert centres. Patients in whom an MRA was performed before and after RDN were included. Scans were evaluated by two independent, blinded radiologists. Primary outcome was the change in renal artery morphology and parenchyma.

Results: MRAs from 96 patients were analysed. Before RDN, 41 renal anomalies were observed, of which 29 mostly mild renal artery stenoses. After a median time of 366 days post RDN, MRA showed a new stenosis (25-49% lumen reduction) in two patients and progression of pre-existing lumen reduction in a single patient. No other renal changes were observed and renal function remained stable.

Conclusions: We observed new or progressed renal artery stenosis in three out of 96 patients, after a median time of 12 months post RDN (3.1%). Procedural angiographies showed that ablations were applied near the observed stenosis in only one of the three patients.

Key Points: • The incidence of vascular changes 12 months post RDN was 3.1%. • No renal vascular or parenchymal changes other than stenoses were observed. • Ablations were applied near the stenosis in only one of three patients.
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http://dx.doi.org/10.1007/s00330-017-4770-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544801PMC
September 2017

Pseudoaneurysms after Ankle Sprain: Report of Three Cases Successfully Cured by Nonsurgical Treatment.

Ann Vasc Surg 2017 Apr 27;40:296.e5-296.e13. Epub 2016 Nov 27.

Département de Radiologie et d'Imagerie Médicale, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium.

Pseudoaneurysm is a rare complication of ankle sprain, with 18 case reports published in the current literature. In the vast majority of the cases, they were treated surgically. We present 3 cases of pseudoaneurysm following ankle sprain, treated by nonsurgical methods in 2 cases, and spontaneously healed in another. The diagnosis was made between 2 and 4 weeks after traumatism, by ultrasonography and arteriography in 2 cases, and only by ultrasonography in a third case. The pseudoaneurysms originated respectively from the perforating fibular artery, the dorsal pedis artery, and a lateral malleolar artery. Largest diameters of the pseudoaneurysms ranged from 2.4 to 6 cm. Patients were successfully treated by thrombin injection in a case and by coil embolization in another. Spontaneous thrombosis was demonstrated at follow-up in the third case. These cases suggest that a nonsurgical treatment can be considered for pseudoaneurysms complicating ankle sprains.
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http://dx.doi.org/10.1016/j.avsg.2016.07.103DOI Listing
April 2017

Renal artery stenosis following renal denervation: a matter of concern.

J Hypertens 2014 Oct;32(10):2101-5

aPole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique bDivision of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium cUniversité Paris-Descartes, Paris Sorbonne Cité dAssistance Publique - Hôpitaux de Paris, European Georges Pompidou Hospital, Interventional Radiology Unit eAssistance Publique - Hôpitaux de Paris, European Georges Pompidou Hospital, Hypertension Unit, Paris, France fDepartment of Radiology Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

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http://dx.doi.org/10.1097/HJH.0000000000000323DOI Listing
October 2014

Rationale and design of the Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial.

Blood Press 2014 06 17;23(3):138-46. Epub 2014 Apr 17.

Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven , Leuven , Belgium.

Unlabelled: The SYMPLICITY studies showed that renal denervation (RDN) is feasible as novel treatment for resistant hypertension. However, RDN is a costly and invasive procedure, the long-term efficacy and safety of which has not yet been proven. Therefore, we designed the INSPiRED trial to compare the blood pressure lowering efficacy and safety of RDN vs usual medical therapy. INSPiRED is a randomized controlled trial enrolling 240 treatment-resistant hypertensive patients at 16 expert hypertension centres in Belgium. Eligible patients, aged 20-69 years old, have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic or more, while taking at least three antihypertensive drugs. They are randomized to RDN (EnligHTN(TM), SJM system) plus usual care (intervention group) or usual care alone (control group) in a ratio of 1:1. The primary endpoints for efficacy and safety, measured after 6 months, are the baseline-adjusted between-group differences in 24h systolic blood pressure and in glomerular filtration rate as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. Follow-up will continue up to 36 months after randomization. INSPiRED is powered to demonstrate a 10-mmHg difference in systolic blood pressure between randomized groups with a two-sided p-value of 0.01 and 90% power. It will generate long-term efficacy and safety data, identify the subset of treatment-resistant hypertensive patients responsive to RDN, provide information on cost-effectiveness, and by doing so INSPiRED will inform guideline committees and health policy makers.

Trial Registration: ClinicalTrials.gov Identifier: NCT 01505010.
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http://dx.doi.org/10.3109/08037051.2014.899297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059255PMC
June 2014

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.

Hum Mutat 2013 Dec 10;34(12):1632-41. Epub 2013 Oct 10.

Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium; Center for Human Genetics, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up.
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http://dx.doi.org/10.1002/humu.22431DOI Listing
December 2013

Reconstructive surgery in the management of a patient with CLOVES syndrome.

J Plast Reconstr Aesthet Surg 2013 Dec 16;66(12):1813-5. Epub 2013 Jul 16.

Center for Vascular Anomalies, Division of Plastic and Reconstructive Surgery, Cliniques universitaires St. Luc, Université catholique de Louvain, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.bjps.2013.06.045DOI Listing
December 2013

Radio-opaque ethylcellulose-ethanol is a safe and efficient sclerosing agent for venous malformations.

Eur Radiol 2011 Dec 7;21(12):2647-56. Epub 2011 Aug 7.

Department of Dermatology, Université de Caen Basse Normandie, CHU Caen, Av Georges Clémenceau, 14033 Caen, France.

Objective: To evaluate the efficacy and safety of gelified ethanol, a newly developed sclerosing agent for slow-flow vascular malformations.

Methods: Seventy-nine sclerotherapy procedures were performed on 44 patients with 37 venous malformations, 2 glomuvenous malformations, 2 lymphatic malformations, 2 lymphatico-venous malformations, and 1 Klippel-Trenaunay syndrome. The median injected volume was 1.00 mL/site of injection. Effects of sclerotherapy on pain, functional and cosmetic disturbance were statistically evaluated with a final result score. Local and systemic complications were recorded.

Results: The mean Visual Analogue Scores were 5.20  ±  2.81 before and 1.52  ±  1.25 after treatment (p < 0.001). Functional and aesthetic improvement was achieved in 31/35 patients (89%) and in 33/41 (80%), respectively. Minor local side effects included necrosis with or without issue of ethylcellulose, palpable residue, and hematoma. No systemic side-effects occurred.

Conclusion: Per mL used, radio-opaque gelified ethanol is at least as effective as absolute ethanol. No systemic complication was observed, as only a low dose of ethanol was injected. Indications for sclerotherapy can be widened to areas with higher risk for local side effects (hands and periocular region), as ethanol is trapped in the lesion. Careful injection procedure is though necessary, because only a limited amount of ethylcellulose can be used per puncture. Key Points • Development of a new sclerosing agent for venous malformations. • Interesting novel way to deliver alcohol to slow-flow vascular malformations. • Alcohol-based with less local and systemic side-effects.
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http://dx.doi.org/10.1007/s00330-011-2213-4DOI Listing
December 2011

Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations.

Hum Mutat 2008 Jul;29(7):959-65

Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one-third had fast-flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast-flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity.
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http://dx.doi.org/10.1002/humu.20746DOI Listing
July 2008

Angiographic documentation of the efficacy of recombinant activated factor VII (NovoSeven) to control diffuse bleeding in major trauma.

Thromb Haemost 2005 Dec;94(6):1327-8

Department of Haematology, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium.

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http://dx.doi.org/10.1160/TH05-06-1327DOI Listing
December 2005

Cerebral microembolization after protected carotid artery stenting in surgical high-risk patients: results of a 2-year prospective study.

J Vasc Surg 2005 Nov;42(5):847-53; discussion 853

Department of Radiology, University Hospital St Luc, Brussels, Belgium.

Background: This was a prospective single-center study to assess and analyze cerebral embolization resulting from carotid artery stenting with neuroprotective filter devices in patients considered as poor surgical candidates for surgical carotid endarterectomy.

Methods: Fifty-three consecutive patients with an internal carotid artery stenosis were treated by placement of carotid Wallstents with two different types of temporary distal filter protection devices: the Spider filter and the FilterWire. Diffusion-weighted magnetic resonance imaging (DWI) of the brain was obtained 24 hours before the procedure and within 5 to 30 hours after the procedure to detect ischemic brain lesions resulting from the procedure. Inclusion criteria were symptomatic (> or =70%) or asymptomatic (> or =80%) stenoses in surgical high-risk patients.

Results: Two (4%) regressive minor strokes occurred. Postprocedural DWI detected new focal ischemic lesions in 21 patients (40%). The average number of lesions was 5.9 per patient, and the mean lesion volume was 1 mL or less in 19 patients (90%). Small differences were found in the lesion distribution: homolateral anterior circulation in eight cases (15.1%), other vascular territories in seven cases (13.2%), and homolateral anterior circulation plus other vascular territories in six cases (11.3%). The microembolization risk seemed nonpredictable on the basis of clinical parameters and internal carotid artery lesion characteristics. An increased risk in the rate of ipsilateral hemispheric embolization has been observed in difficult carotid arch implantations (P = .04).

Conclusions: The incidence of new focal ischemic lesions detected by DWI is higher than expected on the basis of previous reports. Embolization from the aortic arch or common carotid arteries could account for most of those events in patients considered as surgical high-risk patients. Although 90% of the events were clinically silent, this high rate of microembolization raises questions about the possible consequences on cerebral cognitive functions.
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http://dx.doi.org/10.1016/j.jvs.2005.05.065DOI Listing
November 2005

[Rupture of the renal artery and renal parenchyma in a pregnant woman with vascular form of Ehlers-Danlos syndrome].

Prog Urol 2005 Apr;15(2):303-5

Service d'Urologie, Cliniques Universitaires UCL Saint Luc, Bruxelles, Belgique.

A case of intraparenchymal renal haemorrhage associated with renal artery dissection, occurring at the end of pregnancy in a woman with a vascular form of Ehlers-Danlos syndrome is reported for the first time. This cases illustrates the potential risk of this syndrome and the importance of multidisciplinary management to ensure an appropriate diagnostic and therapeutic strategy. Magnetic resonance imaging is useful in this setting to elucidate complex cases of renal colic in pregnant women presenting an increased risk of ischaemic or haemorrhagic disorders.
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April 2005
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