Cephalic arch stenosis in the arteriovenous fistula: A retrospective analysis of predisposing factors

Background: Cephalic Arch Stenosis (CAS) is a frequently observed complication in brachiocephalic and radiocephalic arteriovenous fistulae (AVF) associated with high morbidity and healthcare expenditure. The predisposing factors and preventative strategies for CAS remain unclear. Our aim was to examine predisposing factors for CAS development in the AVF. Methods: A retrospective case-control study was performed at Gold University Coast Hospital on patients with AVFs created from 2009 to 2018 with ⩾18 months follow-up. CAS was defined as a >50% narrowing on angiographic assessment with clinically significant symptoms (dialysis dysfunction, arm swelling, prolonged bleeding after access). Results: About 187 patients with AVF were included in the analysis (36 brachiocephalic, 151 radiocephalic). CAS developed in 22 of 36 (61%) of brachiocephalic AVF and 9 of 151 (6%) of radiocephalic AVFs. Brachiocephalic AVF were ⩾12 times more likely to develop CAS than radiocephalic AVF (Hazard Ratio (HR) 12.7, 95% CI [5.6–28.3], p < 0.001). Each 1 mL/min increase in flow rate through the AVF, correlated with a 0.07% increase in the probability of development of CAS (HR 1.0007, 95% CI [1.0001–1.0012], p = 0.011). Brachiocephalic AVFs with CAS were associated with a higher number of interventional procedures per access-year compared with their non-CAS counterparts (Median [Interquartile range]: 1.76 [0.74, 3.97] vs 0.41 [0.27, 0.67], p = 0.003). Conclusion: Brachiocephalic AVF with higher access flow rates are more likely to develop CAS and earlier than radiocephalic AVF, and in a dose dependent fashion. AVF flow rate is a major factor in CAS development within brachiocephalic AVF and has potential utility in surveillance thresholds for prophylactic blood flow reduction procedures. AVFs with CAS are associated with a greater number of interventional procedures per access-year, heralding higher patient morbidity and healthcare expenditure. Further prospective studies will help define an AVF access flow rate threshold in the implementation of prophylactic strategies for CAS.

ESTIMATION OF PERIODONTAL MICROCIRCULATION, JAW AFTER INJECTION OF ANTI-RESORPTIVE DRUG IN EXPERIMENT

Importance. Determining the influence of different medications in the development of different diseases is a prerequisite for adequate comprehensive treatment of patients. At present, there is insufficient data on the influence of anti-osteoclastic drugs on the microcirculation, which may have an impact. The aim. To study the effects of the monoclonal antibody denosumab on the development of osteonecrosis of the jaw of rats. Methodology. The study was carried out on 36 Wistar Line rats in the Department of Pathophysiology with the course of clinical pathophysiology First Pavlov State Medical University. The osteonecrorosis of the jaws of rats was induced by the extracted of a lower first molar. The observation was carried out with diagnostic studies of microcirculation (doppler), bone structure (3D computer tomography of jaws), followed by statistical processing of the data. Results. It has been shown that the greatest decrease in blood flow rate and the greatest bone defect is determined in the group of rats with the maximum dose of the monoclonal antibody preparation of denosumab by the time of 4 weeks, 0.5 mg/kg intravenous administration. Also, there has been evidence of a difference in blood flow reduction between the histological layers of the lower jaw. Thus, the intrabone blood flow was damaged much more, than the layer of mucous membrane of the gum. Conclusions. The combined method of dopplerography allows the determination of blood flow status on different histological layers. It is possible to determine the extent to which different pharmacological preparations influence the rate of blood flow in the local area without invasive interventions. The study of monoclonal antibodies is an acute problem in the world of surgical dental practice, which requires further study.

A Glyphosate-Based Formulation but Not Glyphosate Alone Alters Human Placental Integrity

Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity.

Hemodynamic Stroke in Simultaneous Cardio Cerebral Infarction: A New Term for Cardiologist

We report an uncommon case of simultaneous cardio-cerebral infarction, due to Inferior – right ventricle ST Segment Elevation Myocardial Infarction (STEMI) with acute ischemic stroke. Incidence of cardio cerebral infarction is exceptionally rare, with an incidence rate as low as 0.009%. Hemodynamic compromise in patients with acute myocardial infarction may result in the cerebral blood flow reduction that cause hemodynamic stroke. Due to the rarity of this condition, there were no recommended therapeutics strategy. Mechanical reperfusion with PCI procedure may be a superior choice in the settings of acute cardio-cerebral infarction for restoring hemodynamic stability.

Pathophysiology of High Flow Access and Surgical Flow Reduction Procedures

High flow access (HFA) is a condition in which hemodynamics is affected by a flow rate that is larger than the blood flow required for hemodialysis. HFA sometimes causes high output heart failure, venous hypertension, and dialysis access steal syndrome. Flow reduction is effective for improving symptoms, and various surgical procedures have been reported. HFA is recognized as a well-developed type of access due to its good access sound, thrill, and vessel diameter; also, HFA probably has good patency if not intervened with by flow reduction. Therefore, the blood flow reduction procedures used to treat HFA need to minimize disadvantages such as access thrombosis, insufficient blood flow, aneurysm formation, and infection due to therapeutic intervention while, at the same time, achieving symptom improvement and long-term patency. The surgical procedure used to correct HFA must be highly reproducible and simple. This article reviews the pathophysiology and surgical flow reduction procedures for HFA.

MO764AVF VOLUME BLOOD FLOW REDUCTION AS THE FIRST STAGE OF TREATMENT OF CENTRAL VEIN STENOSIS IN HD PATIENTS

Background and Aims It is well-known that central vein stenosis (CVS) significantly reduces the time of AVF functioning. At the same time, according to current guidelines (KDIGO, European Vascular Surgery Society, European Best Clinical Practice), only clinically significant CVS should be treated. Often, CVS becomes clinically manifest due to a significant increase of AVF volume blood flow (Qa) through the matured dialysis access. Aim: to assess the effect of Qa reduction on the CVS clinical course. Method We performed a retrospective study included 56 patients who underwent Qa reduction as the first step of treatment, and 62 patients who received endovascular interventions without Qa reduction (balloon angioplasty supplemented with stenting if necessary). Blood flow reduction was performed using banding under intraoperative ultrasound control. Results Surgical banding leads to a clinically obvious and statistically significant decrease in Qa in all patients – fig. 1. In contrast, after endovascular intervention most of the patients show a modest but statistically significant increase in Qa - fig. 2. All surgeries were performed to reduce the severity of clinical manifestations of CVS. AVF was better available for immediate cannulation after endovascular interventions than after banding: RR=4,537 [95%CI 1,416; 14,84], p=0,0116. However, the probability of successful cannulation at the third postoperative HD session did not differ between groups: RR=3.024 [95%CI 0.674; 13.67], p=0.2126. Taking in consideration these findings, we can conclude that the short-term results of Qa reduction are satisfactory. After Qa reduction in case of recurrence of CVS symptoms or absence of their complete resolving, we supplemented the treatment with endovascular interventions. Both primary and secondary patency were significantly better than in the case of endovascular interventions without Qa reduction – fig. 3. Moreover, in patients who underwent endovascular interventions without Qa reduction, higher Qa values were associated with decrease of the primary and secondary patency – fig. 4. So, increasing or maintaining large Qa values after endovascular intervention may be an important risk factor for CVS relapse and AVF function loss. Conclusion Qa is an important factor of CVS clinical manifestation. When determining treatment strategy, it is necessary to evaluate Qa first and reduce it, if necessary. Manage of Qa allows to transfer manifest CVS into its subclinical course, which itself leads to improved treatment results. Endovascular interventions are the preferred treatment of CVS with clinical manifestations in a case of underlying normal or suboptimal Qa.

Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice

Introduction Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer’s disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. Methods In a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, we examined the time courses of microvascular injury, blood–brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also evaluated the BBB integrity, amyloid pathology as well as cognitive functions after mTBI in the 5xFAD mouse model of AD. Results mTBI induced microvascular injury with BBB breakdown, pericyte loss, basement membrane alteration and cerebral blood flow reduction in mice, in which BBB breakdown preceded gliosis. More importantly, mTBI accelerated BBB leakage, amyloid pathology and cognitive impairment in the 5xFAD mice. Discussion Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.

Svep1 stabilizes developmental vascular anastomosis in reduced flow conditions

We report the discovery that flow and Svep1 are modulator of vessel anastomosis during developmental angiogenesis in zebrafish embryos. We show that loss of Svep1 and blood flow reduction both contribute to defective anastomosis of intersegmental vessels. We show that this defect in primary angiogenic sprouts is associated with an expansion of Apelin-positive tip cells and with reduced formation and lumenisation of the dorsal longitudinal anastomotic vessel. Mechanistically, our results suggest that flow and Svep1 act synergistically to modulate vascular network formation in the zebrafish trunk.

Abstract P140: Do Perfusion Computed Tomography Abnormalities in Patients With Transient Ischemic Attack Predict Subsequent Ischemic Stroke and Cardiovascular Event

Background and purpose: To determine if computed tomography (CT) perfusion (CTP) abnormalities in patients with transient ischemic attacks (TIA) are associated with development of ischemic strokes or adverse cardiovascular events within 24 months. Methods: Patients with a diagnosis of TIA who underwent CTP within 24 hours of symptom onset as part of the stroke/TIA imaging protocol were analysed. Abnormality was defined as an area of well demarcated mean transit time delay and/or cerebral blood flow reduction corresponding to an arterial territory as identified by an independent neuroradiologist. The patients were followed for at least 3 months and up to 24 months to identify occurrence of ischemic stroke and cardiovascular events (myocardial infarction or ischemia). Results: A total of 78 patients (mean age 67.60 +/- 15.1 ; 48 were men) with a diagnosis of TIA. A total of 17 patients (22%) had documented CTP abnormalities. Patients with CTP abnormalities were older and more likely to be men. There was no difference in the rates of ischemic stroke (5.9 % vs 3.3 %), or cardiovascular events (0% versus 1.6 %) when patients with CTP abnormalities were compared to those with normal CTP. Conclusions: In patients with TIA, an abnormal CTP does not predict the occurence of new ischemic stroke or cardiovascular events during follow up.

Accelerated brain aging and cerebral blood flow reduction in persons with HIV

Background Persons with HIV (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between HIV and aging. However, it remains unclear how brain aging varies with viral load (VL). Methods In this study, we compare MRI biomarkers amongst PWH with undetectable VL (UVL; ≤50 genomic copies/ml; n=230), PWH with detectable VL (DVL; &gt;50 copies/ml; n=93), and HIV uninfected (HIV-) controls (n=206). To quantify gray matter cerebral blood flow (CBF), we utilized arterial spin labeling. To measure structural aging, we used a publicly available deep learning algorithm to estimate brain age from T1-weighted MRI. Cognitive performance was measured using a neuropsychological battery covering five domains. Results Associations between age and CBF varied with VL. Older PWH with DVL had reduced CBF vs. PWH with UVL (p=0.02). Structurally predicted brain aging was accelerated in PWH vs. HIV- controls regardless of VL (p&lt;0.001). Overall, PWH had impaired learning, executive function, psychomotor speed, and language compared to HIV- controls. Structural brain aging was associated with reduced psychomotor speed (p&lt;0.001). Conclusions Brain aging in HIV is multifaceted. CBF depends on age and current VL, and is improved by medication adherence. By contrast, structural aging is an indicator of cognitive function and reflects serostatus rather than current VL.