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Purpose: The aim of this study was to assess the initial experience, technical success, and clinical benefit of AneuFix (TripleMed, Geleen, the Netherlands), a novel biocompatible and non-inflammatory elastomer that is directly injected into the aneurysm sac by a translumbar puncture in patients with a type II endoleak and a growing aneurysm., Materials and Methods: A multicenter, prospective, pivotal study was conducted (ClinicalTrials.gov:NCT02487290). Patients with a type II endoleak and aneurysm growth (>5 mm) were included. Patients with a patent inferior mesenteric artery connected to the endoleak were excluded for initial safety reasons. The endoleak cavity was translumbar punctured with cone-beam computed tomography (CT) and software guidance. Angiography of the endoleak was performed, all lumbar arteries connected to the endoleak were visualized, and AneuFix elastomer was injected into the endoleak cavity and short segment of the lumbar arteries. The primary endpoint was technical success, defined as successful filling of the endoleak cavity with computed tomography angiography (CTA) assessment within 24 hours. Secondary endpoints were clinical success defined as the absence of abdominal aortic aneurysm (AAA) growth at 6 months on CTA, serious adverse events, re-interventions, and neurological abnormalities. Computed tomography angiography follow-up was performed at 1 day and at 3, 6, and 12 months. This analysis reports the initial experience of the first 10 patients treated with AneuFix., Results: Seven men and 3 women with a median age of 78 years (interquartile range (IQR), 74-84) were treated. Median aneurysm growth after endovascular aneurysm repair (EVAR) was 19 mm (IQR, 8-23 mm). Technical success was 100%; it was possible to puncture the endoleak cavity of all treated patients and to inject AneuFix. Clinical success at 6 months was 90%. One patient showed 5 mm growth with persisting endoleak, probably due to insufficient endoleak filling. No serious adverse events related to the procedure or AneuFix material were reported. No neurological disorders were reported., Conclusion: The first results of type II endoleak treatment with AneuFix injectable elastomer in a small number of patients with a growing aneurysm show that it is technically feasible, safe, and clinically effective at 6 months., Clinical Impact: Effective and durable embolization of type II endoleaks causing abdominal aortic aneurysms (AAA) growth after EVAR is challenging. A novel injectable elastic polymer (elastomer) was developed, specifically designed to treat type II endoleaks (AneuFix, TripleMed, Geleen, the Netherlands). Embolization of the type II endoleak was performed by translumbar puncture. The viscosity changes from paste-like during injection, into an elastic implant after curing. The initial experience of this multicentre prospective pivotal trial demonstrated that the procedure is feasible and safe with a technical success of 100%. Absence of AAA growth was observed in 9 out of 10 treated patients at 6 months., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.J.J. is in the advisory board of TripleMed B.V. and patent holder of the elastomer formula of the AneuFix material.

With the introduction of modern cone beam computed tomography in the operating room, the benefits of imaging modalities in daily practice are recognized by an increasing number of clinicians. Newer generation imaging modalities include CT needle guidance software, which can aid the operator place the needle correctly during percutaneous intervention. This technique has several advantages over traditional percutaneous interventions, especially for high risk procedures like thoracic sympathectomy. We describe and discuss outcomes and possible advantages of applying CT guided needle placement using needle guidance software (XperGuide®) for percutaneous thoracic sympathetic blockade in 8 patients. Based on our findings, we conclude that the use of high quality imaging and needle guidance software such as XperGuide® may improve patient outcomes, and reduce the risk of adverse effects, providing a relatively easy, safe, and valuable alternative treatment strategy for thoracic sympathectomies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc. on behalf of International Pain & Spine Intervention Society.)

Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Despite much debate, there is little evidence on consequences of consent procedures for residual tissue use. Here, we investigated these consequences for the availability of residual tissue for medical research, clinical practice, and patient informedness., Methods: We conducted a randomised clinical trial with three arms in six hospitals. Participants, patients from whom tissue had been removed for diagnosis or treatment, were randomised to one of three arms: informed consent, an opt-out procedure with active information provision (opt-out plus), and an opt-out procedure without active information provision. Participants received a questionnaire six weeks post-intervention; a subsample of respondents was interviewed. Health care providers completed a pre- and post-intervention questionnaire. We assessed percentage of residual tissue samples available for medical research, and patient and health care provider satisfaction and preference. Health care providers and outcome assessors could not be blinded., Results: We randomised 1,319 patients, 440 in the informed consent, 434 in the opt-out plus, and 445 in the opt-out arm; respectively 60.7%, 100%, and 99.8% of patients' tissue samples could be used for medical research. Of the questionnaire respondents (N = 224, 207, and 214 in the informed consent, opt-out plus, and opt-out arms), 71%, 69%, and 31%, respectively, indicated being (very) well informed. By questionnaire, the majority (53%) indicated a preference for informed consent, whereas by interview, most indicated a preference for opt-out plus (37%). Health care providers (N = 35) were more likely to be (very) satisfied with opt-out plus than with informed consent (p = 0.002) or opt-out (p = 0.039); the majority (66%) preferred opt-out plus., Conclusion: We conclude that opt-out with information (opt-out plus) is the best choice to balance the consequences for medical research, patients, and clinical practice, and is therefore the most optimal consent procedure for residual tissue use in Dutch hospitals., Trial Registration: Dutch Trial Register NTR2982.

The incidence of melanoma has been increasing over the years and it remains, despite the heterogeneous survival for different stages, a disease with high mortality. Dissemination occurs primarily by the lymphatic route, followed by the hematogenous route. Gastrointestinal metastases do occur, but they are mainly intraluminal mucosal melanomas. Peritoneal or primary mucosal melanomas are rare. Only a few cases have been described of patients presenting with acute abdominal pain due to a melanoma. In this report we present a young patient with no prior health problems. Due to silent progression of disease at first, and secondarily avoidance of medical consultation, she finally presented to our emergency department with signs of intestinal perforation. In the operating theater a massive metastasis in the intestines with perforation was seen, as well as many smaller intra-abdominal and cutaneous lesions. Approximately 35 cm of jejunum had to be resected. Furthermore, the primary melanoma on the left forearm was excised and turned out to be in almost complete regression. Although initial recovery after surgery was good, the patient died only one month after presentation due to the advanced nature of her disease, which points to the devastating effect of undiagnosed melanoma and gastrointestinal metastasis. Since the melanoma incidence is rising, similar cases may present in the near future. This emphasizes the importance of proper full physical examination in patients with atypical abdominal symptoms.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Québec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and that it interacts with dynamin-related protein 1, which participates in mitochondrial fission. Fibroblasts from ARSACS patients show a hyperfused mitochondrial network, consistent with defects in mitochondrial fission. Sacsin knockdown leads to an overly interconnected and functionally impaired mitochondrial network, and mitochondria accumulate in the soma and proximal dendrites of sacsin knockdown neurons. Disruption of mitochondrial transport into dendrites has been shown to lead to abnormal dendritic morphology, and we observe striking alterations in the organization of dendritic fields in the cerebellum of knockout mice that precedes Purkinje cell death. Our data identifies mitochondrial dysfunction/mislocalization as the likely cellular basis for ARSACS and indicates a role for sacsin in regulation of mitochondrial dynamics.

Background: The purpose of this study was to characterize ipsi- and contralateral cerebral hemodynamics before and after CEA., Methods: Cerebral blood flow, CBV, and MVTT were measured in 10 patients before and after CEA using PET. Absolute and relative values of these parameters were calculated bilaterally for the entire arterial territories and hemispheres., Results: For all territories in both hemispheres, the mean absolute postoperative CBF was significantly increased compared with preoperative CBF (P < .05). Only in MCA was this increase higher in the ipsilateral than in the contralateral hemisphere (P = .02). Cerebral blood volume was unaffected, whereas MVTT decreased in ipsilateral MCA (P = .05)., Conclusions: The present findings suggest that, on the first day after CEA, absolute CBF is increased in all arterial territories on both ipsi- and contralateral sides, but that there are only minor changes in the relative distribution, whereas the CBV was unaffected.

Background and Purpose: Population screening for aneurysms of the abdominal aorta (AAA) is still not implemented in any country, despite proven benefit both in decreased mortality and in cost effectiveness. Detecting a subpopulation with higher prevalence of AAA may alter this situation., Methods: Between 2002 and 2005, all patients with a stroke or transient ischaemic attack (TIA) admitted to the department of Neurology of a community-based hospital were classified according to the Toast criteria and enrolled in a prospective study to assess the diameter of the abdominal aorta. The diameter was assessed by ultrasonography. A written questionnaire and blood tests were used to assess risk factors., Results: The prevalence of AAA amongst the 499 screened patients in the study was 5.8% [95% confidence interval (CI) 5.6-6.0%]. Of the risk factors or Toast criteria, only male gender and age over 59 years correlated significantly with AAA. In the subgroup of 235 men aged over 59 years, the prevalence of AAA was 11.1% (95% CI 10.4-11.8%)., Conclusion: The prevalence of AAA in men over 59 years of age presenting with a stroke or TIA is nearly twofold increased (11.1%) compared with all patients. Therefore, screening for AAA in this subgroup of patients seems beneficial. However, further studies are needed to confirm this finding and to explore the clinical benefit and cost effectiveness.

An extensive protein-protein interaction network has been identified between proteins implicated in inherited ataxias. The protein sacsin, which is mutated in the early-onset neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay, is a node in this interactome. Here, we have established the neuronal expression of sacsin and functionally characterized domains of the 4579 amino acid protein. Sacsin is most highly expressed in large neurons, particularly within brain motor systems, including cerebellar Purkinje cells. Its subcellular localization in SH-SY5Y neuroblastoma cells was predominantly cytoplasmic with a mitochondrial component. We identified a putative ubiquitin-like (UbL) domain at the N-terminus of sacsin and demonstrated an interaction with the proteasome. Furthermore, sacsin contains a predicted J-domain, the defining feature of DnaJ/Hsp40 proteins. Using a bacterial complementation assay, the sacsin J-domain was demonstrated to be functional. The presence of both UbL and J-domains in sacsin suggests that it may integrate the ubiquitin-proteasome system and Hsp70 function to a specific cellular role. The Hsp70 chaperone machinery is an important component of the cellular response towards aggregation prone mutant proteins that are associated with neurodegenerative diseases. We therefore investigated the effects of siRNA-mediated sacsin knockdown on polyglutamine-expanded ataxin-1. Importantly, SACS siRNA did not affect cell viability with GFP-ataxin-1[30Q], but enhanced the toxicity of GFP-ataxin-1[82Q], suggesting that sacsin is protective against mutant ataxin-1. Thus, sacsin is an ataxia protein and a regulator of the Hsp70 chaperone machinery that is implicated in the processing of other ataxia-linked proteins.

The trafficking of normal cellular prion protein (PrPC) is believed to control its conversion to the altered conformation (designated PrPSc) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrPC on neurons is rapidly and constitutively endocytosed by means of coated pits, a property dependent upon basic amino acids at its N-terminus. Here, we show that low-density lipoprotein receptor-related protein 1 (LRP1), which binds to multiple ligands through basic motifs, associates with PrPC during its endocytosis and is functionally required for this process. Moreover, sustained inhibition of LRP1 levels by siRNA leads to the accumulation of PrPC in biosynthetic compartments, with a concomitant lowering of surface PrPC, suggesting that LRP1 expedites the trafficking of PrPC to the neuronal surface. PrPC and LRP1 can be co-immunoprecipitated from the endoplasmic reticulum in normal neurons. The N-terminal domain of PrPC binds to purified human LRP1 with nanomolar affinity, even in the presence of 1 muM of the LRP-specific chaperone, receptor-associated protein (RAP). Taken together, these data argue that LRP1 controls both the surface, and biosynthetic, trafficking of PrPC in neurons.

Background: A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy., Materials and Methods: Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy)., Results: Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively)., Conclusions: These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.

Background: Hyperhomocysteinaemia is an independent risk factor for atherosclerosis and is thought to induce its effects through causing endothelial dysfunction. We studied the effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on urinary and plasma markers of endothelial function, and on plasma C-reactive protein, a marker of chronic inflammation., Design: We performed a placebo-controlled 2-year trial among 158 healthy siblings of patients with premature atherosclerotic disease to determine the effect of daily folic acid (5 mg) plus vitamin B6 (250 mg) treatment as compared with placebo medication (n = 80) on markers of endothelial function (urinary albumin-to-creatinine ratio and plasma concentrations of soluble E-selectin, soluble vascular cell adhesion molecule-1, von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1) and inflammation (C-reactive protein). Outcome variables were assessed at baseline and after 1 and 2 years of treatment., Results: Fasting homocysteine concentrations ( micromol L-1) at baseline and after treatment were 14.7 +/- 8.2 and 7.4 +/- 1.9 in the vitamin and 14.7 +/- 8.8 and 12.0 +/- 5.4 for the placebo group, respectively. Vitamin treatment was associated with a decreased urinary albumin-to-creatinine ratio at follow up [regression coefficient (beta) -0.20 mg mmol-1 (CI: -0.43-0.03); P = 0.09]. After adjustment for age, sex, baseline concentrations of postmethionine total homocysteine plus the baseline albumin-to-creatinine ratio, the beta was -0.23 mg mmol-1 (CI: -0.43 to -0.02; P = 0.03), which amounts to a decrease of approximately 20%. There was no apparent effect of vitamin treatment on the other markers., Conclusions: Homocysteine-lowering vitamin treatment in healthy siblings of patients with premature atherosclerotic disease is associated with a decreased urinary albumin-to-creatinine ratio, but not with other markers of endothelial dysfunction, or in plasma C-reactive protein. The clinical significance of these findings remains to be determined.

Purpose: To determine the value of magnetic resonance (MR) imaging in the spinal cord to differentiate multiple sclerosis (MS) from other inflammatory disorders and cerebrovascular diseases (together, other neurologic disease [OND])., Materials and Methods: The study population included 66 patients with OND and 25 patients with MS, who were matched for age, sex, and symptom duration or severity. Brain MR imaging included gadolinium-enhanced T1-weighted and dual-echo T2-weighted spin-echo sequences to assess the number, size, and appearance of lesions, contrast enhancement, and compatibility with diagnostic criteria for MS. Spinal cord MR imaging included cardiac-triggered gadolinium-enhanced sagittal T1-weighted spin-echo and dual-echo T2-weighted sequences to assess the general appearance (normal, focal lesion, diffuse abnormality) and number or size of focal lesions. Images obtained in MS and OND patients were compared. Specificity, sensitivity, accuracy, and positive and negative predictive values with MR images were calculated., Results: Brain images were abnormal in all MS patients and in 65% of OND patients. Abnormal cord images were found in 92% of MS and 6% of OND patients. The combination of brain and spinal cord images increased accuracy of diagnosis compared with use of brain images alone., Conclusion: In contrast to MS, cord lesions are very uncommon in OND. This finding can help differentiate these disorders.

Two patients with continuing expansion of an internal iliac artery aneurysm following earlier repair of an aortoiliac aneurysm are described. At the primary operation, inflow to small internal iliac aneurysms had been interrupted by simple proximal ligation only. During follow-up, however, increasing diameter of the by CT-angiography completely thrombosed internal iliac aneurysms required re-operation. The observation of continuing growth of thrombosed internal iliac artery aneurysms following proximal ligation emphasises the danger of persistent collateral circulation and supports the concept of endotension in the absence of endoleak following endovascular AAA repair.

The aim of this study was to determine whether the morphology of the muscular femoral artery in patients with atherosclerosis and hyperhomocysteinemia differs from that of atherosclerotic vessels from patients with normal homocysteine levels. Whole-vessel biopsies of the superficial femoral artery were taken from patients with symptomatic atherosclerotic disease with and without hyperhomocysteinemia and from patients without atherosclerosis from traumatic amputations. The morphology of these specimens was studied qualitatively by light and electron microscopy and quantitatively by light microscopy in combination with a video overlay system. Atherosclerotic lesions in patients with hyperhomocysteinemia were morphologically similar to those in patients with normal homocysteine levels, except for a significantly decreased smooth muscle cell/extracellular matrix ratio of the media in hyperhomocysteinemic patients (P=0.02 versus normohomocysteinemic atherosclerotic group and P=0.001 versus group without a history of cardiovascular disease). Hyperhomocysteinemia is associated with a significant decrease of the smooth muscle cell/extracellular matrix ratio of the media of muscular femoral arteries without significant changes in medial thickness. Further investigations should concentrate on the cause of this newly discovered phenomenon and its impact on vascular compliance.

Background: The aim of this study was to analyse the results of infragenual arterial revascularisation using semiclosed endarterectomy of the superficial femoral artery combined with a short venous bypass in patients with critical leg ischemia and insufficient venous material for a straightforward femorocrural reconstruction., Methods: From December 1990 through December 1998 thirty patients were studied (22 males and 8 females; mean age 65 years, range 31-92 years). The mean follow-up was 26 months (range 1-96 months). Cumulative primary patency and limb salvage rates were calculated according to life-table analysis., Results: The cumulative primary patency was 60.3% at 1 year and 48.4% at 3 years. The limb salvage rate was 68.6% at 1 and at 3 years., Conclusions: In patients with limb-threatening ischemia and lack of venous material for a straightforward venous femorocrural bypass, semi-closed endarterectomy of the superficial femoral artery combined with a short popliteo-crural bypass provides a good alternative.

Objectives: to evaluate the feasibility of treatment of post-catheterisation pseudoaneurysms with duplex-guided thrombin injection., Technique: the technique of duplex-guided injection of thrombin in post-catheterisation pseudoaneurysms of the femoral artery is described and illustrated., Results: between December 1998 and October 1999, eight post-catheterisation pseudoaneurysms of the femoral artery were successfully thrombosed with thrombin injection. One patient developed a new pseudoaneurysm within 6 hours and this was also successfully treated with thrombin. Follow-up duplex-scanning at 3 months revealed no recurrences. No other adverse events occurred., Conclusions: this initial experience suggests that duplex-guided thrombin injection in the treatment of post-catheterisation pseudo-aneurysms is feasible and safe., (Copyright 2000 Harcourt Publishers Ltd.)

Background: Mild hyperhomocysteinaemia (HHC) is associated with an increased risk of premature atherothrombotic cerebrovascular disease. We investigated the clinical efficacy with regard to the incidence of cardiovascular events of treatment of mild HHC with vitamin B(6) plus folic acid., Methods: We studied 224 consecutive patients with clinically manifest atherothrombotic cerebrovascular disease with onset before the age of 56. Follow-up was obtained in 203 (90.6%) patients. At baseline, 52 (25.6%) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B(6) (250 mg) plus folic acid (5 mg); 151 (74.4%) were normohomocysteinaemic (reference group)., Results: During follow-up (median 57 months), 31 (20.5%) of the normo- and 11 (21.2%) of the hyperhomocysteinaemic patients had a new cardiovascular event. The crude incidence rate per person-year for any cardiovascular event was similar in both groups (0.043 [CI, 0.029-0.057] in the normo- vs. 0.045 [CI, 0.021-0. 069] in the hyperhomocysteinaemic group). Multivariate Cox-regression analyses showed that hypertension and cholesterol levels were associated with an increased risk of new cardiovascular events in the total group [relative risk [RR] (yes vs. no), 7.4 (3. 4-16.0) and RR (per 1 mmol/l), 1.9 (CI, 1.4-2.7)]. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.96 (CI, 0.48-1.92)., Conclusion: These data are consistent with a protective effect of treatment with vitamin B(6) plus folic acid in patients with premature atherothrombotic cerebrovascular disease and post-methionine HHC.

Arterial occlusive disease developed after radiation therapy in three patients: a woman aged 56 had a sensation of heaviness in her right arm and bluish-black discolorations of fingers 3 years after radiation therapy for breast carcinoma, and two men aged 46 and 45 years had intermittent claudication 23 and 14 years, respectively, after radiation therapy for testicle malignancy. After creation of a bypass, the symptoms subsided. Radiation-induced arterial disease is a rare complication after radiotherapy and usually presents after a latent period of several years. Arterial lesions induced by radiotherapy may be distinguished from atherosclerotic lesions by their atypical localization, limited to the irradiated sites, and occurrence at an earlier age. Symptoms may be masked by pain, limitation of motion, nerve root damage and lymphoedema and may therefore not always be recognized. Indications for treatment are identical to those for atherosclerotic occlusive disease, but due to increased risk of restenosis, rethrombosis and graft infection, percutaneous transluminal angioplasty (with or without stent), endarterectomy or venous bypass surgery should be preferred to prosthetic bypass material.

Background: A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease., Methods: We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography., Findings: Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively)., Interpretation: Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

Objective: To find out if morbidity and mortality after thoracoabdominal approaches for suprarenal aortic aneurysms are related to the duration of organ ischaemia., Design: Retrospective study., Setting: University hospital, The Netherlands., Subjects: 72 operations for suprarenal aortic aneurysms., Main Outcome Measures: Duration of organ ischaemia, morbidity and mortality., Results: There were 72 patients with 3 group A (Crawford type III), 10 group B (Crawford type IV), 37 group C (supracoeliac), and 22 group D (suprarenal) aneurysms. Median duration of ischaemia was 57 minutes for both the spinal cord and the mesenteric arteries, and 59 and 63 minutes for the right and left renal arteries, respectively. There were 52 major complications in 33 patients. Mesenteric ischaemia of longer than 60 minutes was associated with a significant higher complication rate (21/32, 66% compared with 13/40, 33%, p = 0.01). Spinal cord ischaemia of longer than 60 minutes was not associated with a significantly increased incidence of paraplegia (2/40 compared with 6/32, p = 0.13)., Conclusions: We conclude that with surgery for suprarenal aneurysms a significant higher complication rate is noted with increased duration of mesenteric ischaemia.

Objective: To review our 10-year experience of reconstruction of the supra-aortic trunks., Design: Retrospective study., Setting: Teaching hospital, The Netherlands., Subjects: 47 patients who required reconstruction of the supra-aortic trunks for stenotic or occlusive disease between April 1987 and May 1997., Interventions: Right-sided bifurcation graft through a sternotomy (n = 25), left-sided thoracotomy (n = 1), and extra-anatomic bypass (n = 21)., Main Outcome Measures: Morbidity, mortality, and long term patency., Results: 3 patients died (6%); 7 (15%) developed major complications (leak from the brachiocephalic stump, n = 2, and acute occlusion of the bypass graft, n = 5) all of which were successfully treated by immediate reoperation; and 9 (19%) developed minor complications, all of which resolved within 3 months. The median follow up was 36 months (range 1-108), and the 3-year patency rate was 80%. No patient died during the follow up period, but a further 3 were lost to follow up. The remaining 41 were all assessed by duplex scanning or angiography, and 3 required further operation for recurrent symptoms; 33 remained completely free of symptoms., Conclusion: Symptomatic stenotic or occlusive lesions of the supra-aortic trunks can be treated with acceptable morbidity and mortality, giving long term benefit to patients.

Purpose: To compare the relative value of clinical variables with dobutamine-atropine stress echocardiography to predict cardiac events during long-term follow-up. Dobutamine stress echocardiography is increasingly used for the detection of coronary artery disease, but little is known of its prognostic value., Patients and Methods: A total of 430 patients (310 men; mean age 61 years, range 22 to 90) were enrolled in the study. Patients were referred for chest pain complaints and were unable to perform an adequate exercise stress test. All patients underwent dobutamine-atropine stress test (incremental dobutamine infusion: 10 to 40 micrograms/kg/minute, continued with atropine 0.25 to 1 mg intravenously if necessary to achieve 85% of the age predicted maximal heart rate, without symptoms or signs of ischemia) and clinical cardiac evaluation. Follow-up was 17 +/- 5 months, with a minimum of 6 months; 3 patients were lost to follow-up. Cardiac events were defined as cardiac death, nonfatal myocardial infarction, and coronary revascularization., Results: Seventy-nine cardiac events occurred in 76 patients: cardiac death (n = 11), nonfatal myocardial infarction (n = 18), and coronary revascularization (n = 50). By multivariate regression analysis, the prognostic value of the stress test in addition to common clinical variables was assessed. (1) Cardiac death was predicted by age greater than 70 years (odds ratio 5.6, 1.5 to 20) or new wall motion abnormalities in a study that is normal at rest (odds ratio 4.1, 1.1 to 15). (2) Death or myocardial infarction was predicted by a history of myocardial infarction (odds ratio 4.8, 1.8 to 13) or age greater than 70 years (odds ratio 2.3, 1.1 to 5.4), and the stress test outcome provided no additional information. (3) If all events were combined, only stress test results were prognostic: new wall motion abnormalities in a study that is normal at rest (odds ratio 3.1, 1.9 to 5.1), wall motion abnormalities at rest (wall motion score at rest > or = 1.12) (odds ratio 2.5, 1.4 to 4.0), or any new wall motion abnormalities during stress (odds ratio 2.0, 1.4 to 3.8). The positive predictive value of any new wall motion abnormality during stress for all late cardiac events was 25% (95% confidence interval [CI] 19 to 31) with a negative predictive value of 87% (95% CI 83 to 91)., Conclusion: In a large cohort of unselected patients with chest pain syndromes, new wall motion abnormalities induced by dobutamine provide additional information for late cardiac events, independent of clinical variables.