Aorto-venous fistula between an abdominal aortic aneurysm and an aberrant renal vein: a case report

<p>Abstract</p> <p>Introduction</p> <p>The potential complications of an abdominal aortic aneurysm include rupture, compression of surrounding structures, thrombo-embolic events and fistula. The most common site of arterio-venous fistula is the inferior vena cava. Fistula involving a renal vein is particularly uncommon.</p> <p>Case presentation</p> <p>This report describes a 54-year-old Caucasian woman who was admitted to the emergency department with fatigue, severe dyspnea and bilateral lower limb edema. In the first instance this anamnesis suggested possible heart failure. In fact, our patient presented with multi-organ system failure due to a fistula between an infra-renal aortic aneurysm and an aberrant retro-aortic renal vein.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report of a woman with a fistula between an infra-renal aortic aneurysm and an aberrant retro-aortic left renal vein. Aorto-venous fistulas may be asymptomatic or may present with symptoms characteristic of arterio-venous shunting and/or aneurysm rupture. This type of fistula is a rare cause of heart failure. Clinical examination and imaging are essential for detection.</p

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Current status of 5α-reductase inhibitors in the management of lower urinary tract symptoms and BPH

Benign prostatic hyperplasia (BPH) is a progressive disease that is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. Therefore, the goals of therapy for BPH are not only to improve LUTS in terms of symptoms and urinary flow, but also to identify those patients at a risk of unfavorable disease progression and to optimize their management. This article reviews the current status of therapy with 5 alpha-reductase inhibitors (5ARIs), namely fiasteride and dutasteride, for men with LUTS and BPH. Data from key randomized controlled trials (Oxford level 1b) on the use of 5ARIs are analyzed. The efficacy of 5ARIs either as monotherapy or in combination with alpha(1)-adrenoceptor antagonists in the management of LUTS and the impact of monotherapy and combined therapy on BPH progression are discussed. Further promises, including the withdrawal of the alpha-blocker from the combined medical treatment and the potential clinical implications from the use of 5ARIs for prostate cancer chemoprevention in patients receiving 5ARIs for symptomatic BPH are highlighted. Current evidence shows that 5ARIs are effective in treating LUTS and preventing disease progression and represent a recommended option in treatment guidelines for men who have moderate to severe LUTS and enlarged prostates

The anti-epileptic drug Valproic Acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml) on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion induced by the highest (luteinizing) LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml) VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC) inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Human embryonic stem cell-derived neurons as a tool for studying neuroprotection and neurodegeneration.

The capacity to generate myriad differentiated cell types, including neurons, from human embryonic stem cell (hESC) lines offers great potential for developing cell-based therapies and also for increasing our understanding of human developmental mechanisms. In addition, the emerging development of this technology as an experimental tool represents a potential opportunity for neuroscientists interested in mechanisms of neuroprotection and neurodegeneration. Potentially unlimited generation of well-defined functional neurons from hES and patient specific induced pluripotent (iPS) cells offers new systems to study disease mechanisms, signalling pathways and receptor pharmacology within a human cellular environment. Such systems may help in overcoming interspecies differences. Far from replacing rodent in vivo and primary culture systems, hES and iPS cell-derived neurons offer a complementary resource to overcome issues of interspecies differences, accelerate drug discovery, study of disease mechanism as well as provide basic insight into human neuronal physiology

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Endovascular Repair of Abdominal Aortic Aneurysms with Aortocaval Fistula

AbstractObjectivesTo examine the risk of high-flow type II endoleak following endovascular repair of abdominal aortic aneurysm with aortocaval fistula.DesignCase reports.SubjectsTwo patients with abdominal aortic aneurysms with aortocaval fistula.MethodsBoth patients had an endovascular repair of their aortic aneurysms.ResultsThe aneurysms were successfully treated in both patients, without any endoleak on completion angiography. Apart from a transient type II lumbar endoleak in one of the patients, no endoleak was found after 3 and 12 month follow-up. Seven other cases have been published, reporting one type II and one type Ic endoleak.ConclusionWe found no evidence that endovascular repair of abdominal aortic aneurysm with aortocaval fistula is associated with a higher incidence of persistent endoleak