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Key points Patients with end-stage renal failure need arteriovenous fistulas (AVF) to undergo dialysis. However, AVFs present a high rate of failure as a result of excessive venous thickness. Excessive venous thickness may be a consequence of surgical dissection and change in oxygen concentration within the venous wall. We show that venous cells adapt their metabolism and growth depending on oxygen concentration, and drugs targeting the hypoxic response pathway modulate this response in vitro. We used the same drugs on a mouse model of AVF and show that direct or indirect inhibition of the hypoxia-inducible factors (HIFs) help decrease excessive venous thickness. Hypoxia and HIFs can be targets of therapeutic drugs to prevent excessive venous thickness in patients undergoing AVF surgical creation. Abstract Because the oxygen concentration changes in the venous wall, surrounding tissue and the blood during surgical creation of arteriovenous fistula (AVF), we hypothesized that hypoxia could contribute to AVF failure as a result of neointimal hyperplasia. We postulated that modulation of the hypoxia-inducible factors (HIF) with pharmacological compounds could promote AVF maturation. Fibroblasts [normal human fibroblasts (NHF)], smooth muscle cells [human umbilical vein smooth muscle cells (HUVSMC)] and endothelial cells [human umbilical vein endothelial cells (HUVEC)], representing the three layers of the venous wall, were tested in vitro for proliferation, cell death, metabolism, reactive oxygen species production and migration after silencing of HIF1/2-α or after treatment with deferioxamine (DFO), everolimus (Eve), metformin (Met), N-acetyl-l-cysteine (NAC) and topoisomerase I (TOPO), which modulate HIF-α stability or activity. Compounds that were considered to most probably modify intimal hyperplasia were applied locally to the vessels in a mouse model of aortocaval fistula. We showed, in vitro, that NHF and HUVSMC can adapt their metabolism and thus their growth depending on oxygen concentration, whereas HUVEC appears to be less flexible. siHIF1/2α, DFO, Eve, Met, NAC and TOPO can modulate metabolism and proliferation depending on the cell type and the oxygen concentration. In vivo, siHIF1/2α, Eve and TOPO decreased neointimal hyperplasia by 32%-50%, 7 days after treatment. Within the vascular wall, hypoxia and HIF-1/2 mediate early failure of AVF. Local delivery of drugs targeting HIF-1/2 could inhibit neointimal hyperplasia in a mouse model of AVF. Such compounds may be delivered during the surgical procedure for AVF creation to prevent early AVF failure.

International audience; Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, but 60% of conventional [vein-to-artery (V-A)] AVF fail to mature, and only 50% remain patent at 1 year. We previously showed improved maturation and patency in a pilot study of the radial artery deviation and reimplantation (RADAR) technique that uses an artery-to-vein (A-V) configuration. Here, we show that RADAR exhibits higher rates of maturation, as well as increased primary and secondary long-term patencies. RADAR is also protective in female patients, where it is associated with decreased reintervention rates and improved secondary patency. RADAR and conventional geometries were compared further in a rat bilateral carotid artery-internal jugular vein fistula model. There was decreased cell proliferation and neointimal hyperplasia in the A-V configuration in male and female animals, but no difference in hypoxia between the A-V and V-A configurations. Similar trends were seen in uremic male rats. The A-V configuration also associated with increased peak systolic velocity and expression of Kruppel-like factor 2 and phosphorylated endothelial nitric oxide synthase, consistent with improved hemodynamics. Computed tomography and ultrasound-informed computational modeling showed different hemodynamics in the A-V and V-A configurations, and improving the hemodynamics in the V-A configuration was protective against neointimal hyperplasia. These findings collectively demonstrate that RADAR is a durable surgical option for patients requiring radial-cephalic AVF for hemodialysis access.

Objectives Establish recommendations for the management of UTIs in MS patients. Background Urinary tract infections (UTIs) are common during multiple sclerosis (MS) and are one of the most common comorbidities potentially responsible for deaths from urinary sepsis. Methods The recommendations attempt to answer three main questions about UTIs and MS. The French Group for Recommendations in MS (France4MS) did a systematic review of articles from PubMed and universities databases (01/1980–12/2019). The RAND/UCLA appropriateness method, which has been developed to synthesize the scientific literature and expert opinions on health care topics, was used for reaching a formal agreement. 26 MS experts worked on the full-text review and a group of 70 multidisciplinary health care specialists validated the final evaluation of summarized evidences. Results UTIs are not associated with an increased risk of relapse and permanent worsening of disability. Only febrile UTIs worsen transient disability through the Uhthoff phenomenon. Some immunosuppressive treatments increase the risk of UTIs in MS patients and require special attention especially in case of hypogammaglobulinemia. Experts recommend to treat UTIs in patients with MS, according to recommendations of the general population. Prevention of recurrent UTIs requires stabilization of the neurogenic bladder. In some cases, weekly oral cycling antibiotics can be proposed after specialist advice. Asymptomatic bacteriuria should not be screened for or treated systematically except in special cases (pregnancy and invasive urological procedures). Conclusion Physicians and patients should be aware of the updated recommendations for UTis and MS.

Summary Aims Beside motor control alteration and tremor, the main symptoms in Parkinsonian disorders, lower urinary tract dysfunction is very common and thus often associated with gait disorder. No studies have assessed their association yet. The aim of this study was to assess the effect of the need to void on walking speed in this particular population. The secondary aim was to assess the effect of desire to void in a double task condition on the walking speed, and on the time to raise up from the floor. Methods This prospective study included all Parkinsonian disorders who had a follow-up for overactive bladder (OAB). We invited them to drink until a desire to void or equivalent (DV), then they performed three ten-meters walk tests, one double-task ten-meters walk test, one timed-up-and-go test (TUG), one timed raise of the floor (GMT). We repeated the same tests just after bladder emptying. Results Nine men and two women (age 69 ± 6) were included in the study (seven Parkinson's Diseases, two multisystem atrophies, two not yet characterized). Mean scores of UPDRS-III were 17 ± 6.5, Hoehn & Yahr scale were 1.9 ± 0.7, time since onset 7 ± 4.4 years, levodopa daily equivalent 691 ± 478 mg. Patients performed the walking tests at DV with a mean bladder volume from 220 ± 189 mL. The mean speed was 1 m/s at DV and 1.1 m/s at PV (P Conclusion In Parkinsonian disorders, need to void may impact the walking speed, a strong desire to void worsening gait velocity. Level of evidence 4.

Resume Introduction La demence a corps de Lewy (DCL) est un syndrome parkinsonien, dont nous savons qu’il est pourvoyeur de troubles urinaires et particulierement d’un syndrome clinique d’hyperactivite vesicale. La typologie des troubles neuro-perineaux specifiques a la DCL a ete peu decrite dans la litterature, nous avons donc realise une etude retrospective descriptive de ces troubles. Methode Etude retrospective monocentrique. Resultats Dix-neuf patients ayant un diagnostic confirme de DCL ont ete retrouves, (63 % d’hommes, 74 ans d’âge moyen). Le symptome principal etait le syndrome clinique d’hyperactivite vesicale (100 % des patients) avec une incontinence urinaire sur urgenturie tres frequente (94 %), sous-tendue par une hyperactivite du detrusor (93 %) a haut-regime de pression intra-vesicale (79 %). La dysurie etait retrouvee a l’interrogatoire chez 16 % des patients, et chez 53 % en urodynamique. Au total, 92 % des patients se plaignaient d’une constipation, et notamment 44 % de troubles de la continence aux matieres. Discussion Sur le plan urinaire, le symptome le plus frequemment decrit est l’incontinence sur urgenturie. Nous avons egalement retrouve dans une moindre mesure une dysurie, parfois associee a une pathologie prostatique. Sur le plan topographique, ces symptomes pourraient s’expliquer par des depots d’alpha-synucleine dans le cortex fronto-temporal et le pont. L’association aux troubles ano-rectaux et genito-sexuels est frequente. Le risque uro-nephrologique etant faible dans cette population, l’importance du depistage est plutot lie a l’alteration de la qualite de vie. Conclusion Le symptome urinaire le plus frequent dans la DCL est le syndrome clinique d’hyperactivite vesicale sous-tendu par une hyperactivite detrusorienne et dans une moindre mesure la dysurie avec possible participation organique (hypertrophie prostatique). Niveau de preuve 3.

Purpose The aim of this study was to describe lower urinary tract symptoms in neuromyelitis optica (NMO), and to compare these data with urinary disorders observed in multiple sclerosis (MS) patients. Methods Retrospective study of data collected from January 1997 to July 2017 using the database from a Neuro-Urology Department of a university hospital. NMO and MS patients were matched for sex, age, and Expanded Disability Status Scale (EDSS). Results Twenty-six patients with NMO were included and compared with 33 MS patients. Mean age was 41.6 years (standard deviation [SD], 14,8), mostly female patients (24 vs. 2 males). Mean EDSS was 4.6 (SD, 1.8) in the 2 groups. In NMO group, 57% of the patients (n=15) had overactive bladder with urgency and urge incontinence and 38.5% (n=10) of them had nocturia. Voiding symptoms was observed in 69.2% of the patients (n=18); 42.3% of NMO patients performed self-intermittent catheterization versus 12.1% in MS patients (P=0.012). Low bladder compliance and severe urinary tract infections (pyelonephritis) were more frequent in NMO than in MS patients (respectively 15% vs. 0%, P=0.016 and 42% vs. 12%, P=0.024). Conclusion Lower urinary tract symptoms, especially overactive bladder and urinary retention, are frequent in NMO. Low bladder compliance, serious urinary infections, and high prevalence of urinary retention requiring self-intermittent catheterization are the main symptoms significantly more frequent than in MS.