Creating hemodialysis autogenous access in children and adolescents.

OBJECTIVE: End-stage renal disease (ESRD) in childhood and adolescence is rare, with relatively few published reports of pediatric ESRD vascular access. This study analyzes a 10-year experience creating arteriovenous fistulas (AVFs) in children and adolescents. Our goal is to review our strategy for creating functional autogenous vascular access in younger patients and report our results. METHODS: We retrospectively reviewed data and outcomes for consecutive vascular access patients aged ≤19 years during a 10-year period. Each patient had preoperative vascular ultrasound mapping by the operating surgeon in addition to physical examination. A distal forearm radiocephalic AVF was the first access choice when feasible, and a proximal radial artery inflow AVF was the next option. Demographic data, inflow artery, venous outflow target, and required transposition vs direct AVFs were variables included in the analysis. Primary and cumulative patency were calculated by Kaplan-Meier analysis. RESULTS: Thirty-seven AVFs were created in 35 patients. No grafts were used. Ages were 6 to 19 years (mean, 15 years), and 20 were male. Causes of ESRD included glomerular disease (n = 18) and urinary obstruction or reflux (n = 7), among others. Three had previous AVFs, and 10 were obese. The proximal radial artery supplied AVF inflow in 25 patients and the brachial artery in only seven. Eleven individuals required a transposition and one a vein translocation to the contralateral arm. No patients developed hand ischemia, although two later required banding procedures for high flow. Eleven patients had successful transplants. A single patient died, unrelated to the vascular access. Five AVFs failed. Of these, two had new successful AVFs created, two regained renal function, one was transplanted, and one declined other procedures. Primary and cumulative patency rates were 75% and 85% at 12 months, 70% and 85% at 24 months, and 51% and 85% at 36 months, respectively. Median follow-up was 16 months. CONCLUSIONS: Creating an AVF for hemodialysis is a successful vascular access strategy for pediatric and adolescent patients. Proximal radial artery AVFs provided safe and functional access when a distal AVF was not feasible. Cumulative AVF patency was 85% at 36 months.

Vascular Surgery Training Positions and Applicant 10-Year Trends with Consideration for Further Expansion.

BACKGROUND: There is a significant shortage of vascular surgeons in the United States and projections for these practicing surgical specialists continue to worsen. Annual appraisal of our workforce recruitment and growth is imperative. MATERIALS AND METHODS: Retrospective data were analyzed using the National Resident Matching Program from 2012-2022 applicant appointment years (specialty code for vascular surgery 450). Simple linear trend analysis was performed for the number of positions available and the number of applicants, stratified by fellowship or residency. RESULTS: Over the 10-year study period, the total vascular surgery trainee positions expanded from 161 to 202. Integrated residency positions increased (41 positions in 2012 vs. 84 in 2022) while available fellowship positions remained stagnant (120 in 2012 vs. 118 in 2022). Total applicants rose as well, from 213 to 311. In 2022, unmatched applicants have increased for both paradigms (25 fellowship and 84 residency applicants) and 100% of programs filled. On average, the number of residency positions offered increased by 4 each year (P < 0.0001) and the number of fellowship positions increased by 0.5 each year (P = 0.1617). The number of integrated residency applicants increased by approximately 9 per year (P = 0.001), while the number of fellowships applicants increased by approximately 1.5 per year (P = 0.121). CONCLUSIONS: Applicants for both vascular tracks have increased since 2012 indicating successful recruitment; however, all 2022 programs filled, leaving many applicants unmatched. Residency positions have continued to expand while fellowship positions have not. With the demonstrated surge among applicants, the disproportionate lack of increasing training positions, and the existing shortage of vascular surgeons, there is an urgency to meet the increasing demand. A concerted effort should be made toward adding additional residency and fellowship positions where feasible.

Long-Term Results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access.

PURPOSE: To report the 5-year results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula (pAVF) Creation for Hemodialysis Access. MATERIALS AND METHODS: The retrospective review of 107 intent-to-treat (ITT) patients from the pivotal trial provided a long-term follow-up population (LTP) of 85 patients with a median follow-up duration of 50 months (range, 12-60 months). Data evaluated in the LTP group were fistula maturation and usage, secondary procedures, and complications. The Kaplan-Meier analysis of primary patency, assisted primary patency, cumulative patency, and functional patency (time from 2-needle cannulation to abandonment) were performed for the ITT population. RESULTS: In the LTP, 99% (84 of 85) of fistulae were mature, with 99% (78 of 79) of patients requiring hemodialysis using their pAVF. Sustained fistula use (2-needle cannulation at the prescribed rate, 2 of 3 sessions) was achieved in 92% (78 of 85) of patients, with 7 patients not using their pAVF because they were not on dialysis (n = 4), were on peritoneal dialysis (n = 2), and refused to use fistula (n = 1). Fistula maintenance was required in 31.8% (27 of 85) of patients and included fistula dysfunction (21.2%), thrombosis (5.9%), cannulation injury (12.9%), and arm swelling (4.7%). The number of procedures performed per patient per year to maintain function and patency was 0.32 (91 of 288) for years 2-5. The cumulative patency rates were 89.5%, 88.4%, 88.4%, 85.6%, and 82.0% for years 1, 2, 3, 4, and 5, respectively. The functional patency was 91.8% at the end of the study. There were no major complications related to pAVF during the long-term follow-up. CONCLUSIONS: Percutaneous fistulae have provided clinically effective and durable access for hemodialysis with low complications. The continued use and evaluation of pAVF are warranted.

Autogenous Vascular Access in American Indians.

BACKGROUND: American Indians (AI) or Alaska Natives, or in combination with another race, comprised 6.8 million individuals in 2010 and the population is expected to exceed 10 million in the current census. Diabetes is more common in AIs than in other races in the United States and is responsible for 69% of new onset end stage renal disease in AI patients. The incidence of obesity is also higher among AIs. As both diabetes and obesity make creating a successful autogenous vascular access more challenging, we reviewed our experience creating arteriovenous fistulas in AI patients. METHODS: Our vascular access database was reviewed for consecutive new AI patients undergoing creation of a hemodialysis vascular access during a 10-year period. Each patient underwent ultrasound vessel mapping by the operating surgeon in addition to history and physical examination. The goal for initial cannulation was 4-6 weeks after access creation. Minimal AVF flow volume for cannulation was 500 mL/min with an outflow vein diameter of 6 mm. RESULTS: 235 consecutive new AI patients were identified. All patients had an autogenous access constructed. The median age was 56 years (range, 15-89 years). Diabetes was present in 85% and 42% were female. Obesity was noted in 27% of the patients and 37% had previous vascular access operations. Primary patency at 12 and 24 months was 62% and 46%, respectively. Cumulative patency at 12 and 24 months was 96% and 94%, respectively. Female gender and previous access operations were associated with lower primary (P = 0.002 and 0.02, respectively) and cumulative patency (P = 0.01 and 0.04, respectively). Obesity was associated with lower cumulative access patency (P = 0.02). Overall, 74% of the access operations used the radial or ulnar artery for AVF inflow. Distal radial artery inflow AVFs were associated with longer patient survival (P = 0.01) and individuals with proximal radial inflow had longer survival when compared to brachial artery AVFs. Previous access operations were associated with shorter patient survival (P = 0.04). CONCLUSIONS: Safe and functional arteriovenous fistulas can be created for American Indians despite a higher prevalence of vascular access risk factors such as diabetes and obesity.

Comparison of Ellipsys Percutaneous and Proximal Forearm Gracz-Type Surgical Arteriovenous Fistulas.

RATIONALE & OBJECTIVE: Percutaneous arteriovenous fistulas (AVF) are created by establishing a proximal forearm anastomosis and offer a safe and reliable vascular access. This study compares the Ellipsys percutaneous AVF with a proximal forearm Gracz-type surgical AVF, chosen for comparison as it is constructed at the same anatomical site. STUDY DESIGN: Retrospective study of prospectively collected clinical data. SETTING & PARTICIPANTS: All vascular access procedures conducted during a 34-month period were reviewed. The study groups comprised 89 percutaneous AVFs and 69 surgical AVFs. EXPOSURE: Percutaneous or surgical AVF placement. OUTCOME: AVF patency, function, and complications. ANALYTICAL APPROACH: Patency rates for each AVF group were evaluated by competing risk survival analysis using a cumulative incidence function. Association of primary, primary assisted, and secondary patency with the AVF groups was examined by Cox proportional hazard models. RESULTS: Technical success was 100% for both groups. Average procedure times were 14 minutes for percutaneous AVFs and 74 minutes for surgical AVFs (P < 0.001). Proximal radial artery (PRA) was used in all percutaneous AVF cases. Inflow for surgical AVFs included radial (30%), ulnar (12%), and brachial (58%) arteries. Outflow veins for both groups were the cephalic and/or basilic veins. Access flow volumes, times to maturation, and overall numbers of interventions per patient-year were not significantly different. Cumulative incidence of primary patency failure at 12 months was lower for surgical AVF (47% vs 64%, P = 0.1), but secondary patency failure was not different between groups (20% vs 12%, P = 0.3). PRA surgical AVFs had similar primary patency (65% vs 64%, P = 0.8) but higher secondary patency failure rates than percutaneous AVFs at 12 months (34% vs 12%, P = 0.04). LIMITATIONS: Retrospective study with a relatively short follow-up period, and not all patients required hemodialysis at the end of study. CONCLUSIONS: Both percutaneous and surgical AVFs demonstrated high rates of technical success and secondary patency. Percutaneous AVFs required shorter procedure times. The rate of intervention was similar. When a distal radial artery AVF is not feasible, percutaneous AVF might offer an appropriate procedure for creating a safe and functional access, maintaining further proximal forearm surgical AVF creation options.

Comparison of surgical versus percutaneously created arteriovenous hemodialysis fistulas.

OBJECTIVE: The aim of the present study was to compare the results between percutaneous arteriovenous fistulas (p-AVFs) created with the Ellipsys device (Ellipsys Vascular Access System; Avenu Medical, San Juan Capistrano, Calif) and surgical arteriovenous fistulas (s-AVFs). METHODS: A single-center retrospective comparative study of the first 107 patients who had undergone p-AVF creation with the Ellipsys system from May 2017 to May 2018 with an equal number of consecutive patients who had undergone s-AVF creation in our center during the same period. The primary endpoints included the maturation and patency rates. The secondary endpoints were reintervention, risk of infection, and the incidence of steal syndrome and aneurysm formation. RESULTS: The demographic, hypertension, and diabetes data were similar for both groups. The only difference between the two groups was that more p-AVF patients had already been receiving hemodialysis (61% vs 47%; P < .05). The p-AVFs showed superior maturation rates at 6 weeks (65% vs 50%; P = .01). The primary patency rates were greater for the s-AVFs at 12 months (86% vs 61%; P < .01). However, primary patency was comparable between the two groups at 24 months (52% vs 55%; P = .48). No significant difference was found in the secondary patency rates at 12 (90% vs 91%) and 24 (88% vs 91%) months. At the 2-year follow-up point, the rate of percutaneous reintervention was similar; however, the s-AVFs had required more frequent surgical revision (36% vs 17%; P = .01). Issues with wound healing and infection were also more frequent with s-AVFs (9% vs 0.9%; P < .01). CONCLUSIONS: Fistulas created percutaneously with the Ellipsys system showed superior maturation rates and similar patency with s-AVFs created in an experienced high-volume vascular surgery practice. p-AVFs had a lower risk of wound healing issues, infection, and surgical revision. Larger, prospective, randomized multicenter studies are needed to confirm these findings.

Midterm results of percutaneous arteriovenous fistula creation with the Ellipsys Vascular Access System, technical recommendations, and an algorithm for maintenance.

OBJECTIVE: The aim of this study was to report our midterm results of percutaneous arteriovenous fistula (pAVF) creation using the Ellipsys (Avenu Medical, San Juan Capistrano, Calif) device and to present technical recommendations and our algorithm of pAVF maintenance. METHODS: A single-center comprehensive database of all consecutive predialysis and end-stage renal disease patients who had a pAVF creation with the Ellipsys device was reviewed retrospectively. Study end points included technical success, maturation, functional patency, and required interventions. RESULTS: Between May 2017 and July 2019, there were 234 patients (mean age, 64 years; 148 male [63%]) who had a pAVF created. Technical success was achieved in 232 individuals (99%), and average duration of the procedure was 15 minutes (7-35 minutes). Average follow-up was 252 days (range, 83-696 days). The 1-year primary, primary assisted, and secondary patency rates were 54%, 85%, and 96%, respectively. Average pAVF flow was 923 mL/min (range, 425-1440 mL/min). There were no significant adverse events related to the procedure. Only three patients (1%) required a later conversion of the pAVF anastomosis to a surgical fistula. Twenty-four (10%) patients required superficialization of deep outflow veins because of difficult cannulation. Average maturation time was 4 weeks (range, 1-12 weeks). Fourteen patients (6%) had early (<2 weeks after creation) cannulation of the pAVF. CONCLUSIONS: The Ellipsys pAVF device allows the rapid and safe creation of a reliable autogenous access. Rates of technical success, patency, and maturation were excellent. For patients unsuited for a distal radiocephalic arteriovenous fistula, it should be considered the next preferred access option.

Comparison of Outcomes of Percutaneous Arteriovenous Fistulae Creation by Ellipsys and WavelinQ Devices.

PURPOSE: The purpose of this study was to compare the clinical outcomes of Ellipsys with those of WavelinQ-4F percutaneous arteriovenous fistulae (pAVF) devices in a single center by a single operator. MATERIALS AND METHODS: A retrospective review was conducted in 100 patients who underwent pAVFs procedures (65 Ellipsys and 35 WavelinQ patients) and created between December 2017 and December 2019. A total of 69% were male and 37% were diabetic. Median age was 64.1 years (range: 28-86), and median body mass index was 27.2 (range: 15-45.1) kg/m2. A procedure sequence algorithm was followed for selecting all vascular accesses created. RESULTS: Ellipsys outcomes were compared to WavelinQ outcomes. Technical success was 100% versus 97%, respectively, and median procedure times were 14 versus 63 minutes, respectively (P < .001), with 183 (1-487) versus 185 (0-760) days follow-up, respectively. Maturation at 4 weeks was 68.3% versus 54.3%, respectively, and median times to cannulation were 60 (1-164) versus 90 (1-180) days, respectively. Successful pAVF dialysis was established in 31 of 39 patients (79.5%) versus 14 of 24 patients (58%), respectively (P = .071), dialysis patients with access-related adverse events observed in 4 individuals (1 Ellipsys versus 3 WavelinQ). Six patients (5 versus 1) with matured outflow from previous AVFs underwent first-day cannulations. Interventions were performed in 27.7% (33 Ellipsys) and 26.5% (15 WavelinQ) patients, and the number of interventions per patient-years was 0.96 versus 0.46, respectively. pAVF failure was seen in 15.4% versus 37.1% patients, respectively (P = .0137). Secondary patency at 12 months was significantly higher among patients who had an Ellipsys procedure (82%) than among those who underwent the WavelinQ procedure (60%). CONCLUSIONS: pAVFs were created with high technical success and low complications with both devices. Ellipsys pAVFs demonstrated significantly shorter procedure times without a need for radiation exposure and with superior secondary patency.

Membrane curvature allosterically regulates the phosphatidylinositol cycle, controlling its rate and acyl-chain composition of its lipid intermediates.

Signaling events at membranes are often mediated by membrane lipid composition or membrane physical properties. These membrane properties could act either by favoring the membrane binding of downstream effectors or by modulating their activity. Several proteins can sense/generate membrane physical curvature (i.e. shape). However, the modulation of the activity of enzymes by a membrane's shape has not yet been reported. Here, using a cell-free assay with purified diacylglycerol kinase ϵ (DGKϵ) and liposomes, we studied the activity and acyl-chain specificity of an enzyme of the phosphatidylinositol (PI) cycle, DGKϵ. By systematically varying the model membrane lipid composition and physical properties, we found that DGKϵ has low activity and lacks acyl-chain specificity in locally flat membranes, regardless of the lipid composition. On the other hand, these enzyme properties were greatly enhanced in membrane structures with a negative Gaussian curvature. We also found that this is not a consequence of preferential binding of the enzyme to those structures, but rather is due to a curvature-mediated allosteric regulation of DGKϵ activity and acyl-chain specificity. Moreover, in a fine-tuned interplay between the enzyme and the membrane, DGKϵ favored the formation of structures with greater Gaussian curvature. DGKϵ does not bear a regulatory domain, and these findings reveal the importance of membrane curvature in regulating DGKϵ activity and acyl-chain specificity. Hence, this study highlights that a hierarchic coupling of membrane physical property and lipid composition synergistically regulates membrane signaling events. We propose that this regulatory mechanism of membrane-associated enzyme activity is likely more common than is currently appreciated.

Structural snapshot of the cholesterol-transport ATP-binding cassette proteins 1.

The ATP-binding cassette (ABC) proteins play critical roles in maintaining lipid and sterol homeostasis in higher eukaryotes. In humans, several subfamily-A and -G members function as cholesterol transporters across the cellular membranes. Deficiencies of these ABC proteins can cause dyslipidemia that is associated with health conditions such as atherosclerosis, diabetes, fatty liver disease, and neurodegeneration. The physiological roles of ABC cholesterol transporters have been implicated in mediating cholesterol efflux for reverse cholesterol transport and in maintaining membrane integrity for cell survival. The precise role of these ABC transporters in cells remains elusive, and little is known about the sterol-transport mechanism. The membrane constituents of ABC transporters have been postulated to play a key role in determining the transport substrates and the translocation mechanisms via the transmembrane domains. Recent breakthroughs in determining high-resolution structures of the human sterol transporter ABCG5/G8 and its functional homologs have shed light on new structural features of ABC transporters, providing a more relevant framework for mechanistic analysis of cholesterol-transport ABC proteins. This minireview outlines what is known about ABCG cholesterol transporters, addresses key structural features in the putative sterol translocation pathway on the transmembrane domains, and concludes by proposing a mechanistic model of ABC cholesterol transporters.

Creating arteriovenous fistulas for children in Guatemala.

OBJECTIVE: The Guatemalan Foundation for Children with Kidney Diseases was established in 2003 as the first and only comprehensive pediatric nephrology program and hemodialysis unit in Guatemala. Bridge of Life (BOL) is a not-for-profit charitable organization focused on chronic kidney disease and supplied equipment, training and support during formation of the hemodialysis unit. Pediatric permanent vascular access (VA) expertise had not been established and noncuffed dialysis catheters provided almost all VA, many through subclavian vein access sites. BOL assistance was requested for establishing a VA surgical program, resulting in recurring BOL surgical missions to create arteriovenous fistulas (AVF) in these children. This study analyzes the BOL pediatric VA missions to Guatemala. METHODS: Three surgical pediatric VA missions were conducted in Guatemala from 2015 to 2017. Each mission was led by two or three surgeons. All supplies and equipment (including ultrasound units) were taken as part of each mission. The BOL surgical VA mission teams work with local pediatric surgeons, pediatric nephrologists, and dialysis nurses to establish collegial relationships and foster teaching interactions. We retrospectively reviewed the patient demographic data, procedures, and outcomes for these missions. RESULTS: AVFs were created in 54 new pediatric patients. Ages were 8 to 19 years (13.4 ± 2.8 years) and 29 patients (54%) were male. Patient weights were 28 to 50 kg (30.8 ± 8.3 kg) with body mass indexes of 12 to 25 kg/m2 (17.9 ± 2.9 kg/m2). Radiocephalic AVFs were created in 21 children (39%), proximal radial artery AVFs in 12 (22%). and brachial artery inflow AVFs in 5 (9%). Sixteen patients (30%) required transpositions and one a translocation; two of these were femoral procedures. Primary and cumulative patency rates were 83% and 85% at 12 months and 62% and 85% at 36 months, respectively. The median follow-up was 17 months. Interventions with fistulagram and balloon angioplasty options were not available for AVF dysfunction or access salvage during the study period. However, six patients underwent an AVF revision and salvage during subsequent missions or by one of the Guatemalan surgeons (R.S.). Four individuals underwent successful transplantation during the study period. There were no operative deaths or major complications. CONCLUSIONS: Pediatric VA missions to Guatemala created safe and functional AVFs in concert with local pediatric surgeons and pediatric nephrologists. Three surgical missions included access operations in 54 new patients. Cumulative AVF patency was 85% at 36 months.

Proximal radial artery arteriovenous fistula for hemodialysis vascular access.

OBJECTIVE: This study reviewed our experience with proximal radial artery-based arteriovenous fistulas (PRA-AVFs) for hemodialysis vascular access, evaluating characteristics of the patients, functional patency, risk of steal syndrome, survival of the patient, and technical considerations. METHODS: We retrospectively analyzed our database of consecutive patients, identifying those individuals with a PRA-AVF created during a 12-year period. In addition to physical examination, all patients underwent ultrasound vessel mapping by the operating surgeon, identifying the PRA-AVF configuration and outflow target most likely to succeed. RESULTS: PRA-AVFs were created in 1396 individuals during the 12-year study period. The mean age was 59 years (standard deviation, ±15.9 years); 717 (51%) patients were women, 819 (59%) were diabetic, and 394 (28%) were obese. A transposition procedure was required in 400 patients, and 189 (47%) of these were completed in two-staged operations. Preoperative characteristics with a negative impact on PRA-AVF cumulative patency included female gender (hazard ratio, 1.90; 95% confidence interval, 1.37-2.65), obesity (hazard ratio, 1.92; 95% confidence interval, 1.40-2.65), and younger age. Dialysis-associated steal syndrome (DASS) requiring an intervention occurred in 39 (2.8%) patients, and 85% of these were diabetic. The most common procedures required to restore hand perfusion while preserving the AVF were banding and outflow branch ligation or coil occlusion to decrease access flow. DASS emerged spontaneously in 15 (1.1%) of the patients, and 24 (1.7%) individuals developed hand ischemia requiring intervention after fistulography with balloon angioplasty of the PRA-AVF anastomosis during the first years of the study period. Limiting angioplasty balloon size for such patients avoided these uncommon angioplasty-induced DASS events in later years. Primary, primary assisted, and cumulative (secondary) patency rates were 60%, 90%, and 93% at 12 months and 47%, 86%, and 91% at 24 months, respectively. Follow-up was 0.7 to 127 months (median, 25 months). CONCLUSIONS: PRA-AVFs offer excellent functional patency with low risk of dialysis access-related steal syndrome. The antecubital site has a wide range of venous outflow options for both direct PRA-AVFs and transposition procedures.

Early results of percutaneous arteriovenous fistula creation with the Ellipsys Vascular Access System.

OBJECTIVE: We reviewed our initial experience creating a percutaneous arteriovenous fistula (pAVF) using a thermal resistance anastomosis device with proximal radial artery inflow. METHODS: A retrospective review was conducted of all patients who underwent a pAVF creation procedure between May 2017 and October 2017. Primary end points of the study were technical success, patency by Doppler ultrasound examination or angiography, flow levels achieved, time to first use, and pAVF-related complications. RESULTS: A pAVF was attempted in 34 patients with technical success in 33 individuals (97%). Patency of the pAVF was 94%. Mean access flow was 946 mL/min (brachial artery measurement) at the latest follow-up visit (53-229 days; average, 141 days). At 6 weeks, all fistulas have been used or were ready for dialysis by clinical examination or ultrasound examination. Only one patient required superficialization of the upper arm cephalic vein by lipectomy. There were no adverse events related to the pAVF creation or use, nor was there need for further interventions. CONCLUSIONS: Successful pAVFs with proximal radial artery inflow were created with excellent initial results regarding technical success, patency, and safety. Advantages include avoidance of a surgical incision, short procedure times, good acceptance by patients, prompt access maturation, moderate flow, and low-pressure access, with possible reduction of risk for ischemic complications. Avoidance of vessel manipulation and side branch ligation might reduce risk of thrombosis and improve long-term patency and reduce need for further interventions. These early findings need to be confirmed in larger and longer follow-up studies.

The Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access.

PURPOSE: To evaluate safety and efficacy of arteriovenous fistulas (AVFs) created with a thermal resistance anastomosis device. MATERIALS AND METHODS: A prospective single-arm trial at 5 sites enrolled 107 patients. Patients underwent ultrasound (US)-guided anastomosis creation between the proximal radial artery and perforating vein with the Ellipsys Vascular Access System (Avenu Medical, Inc, San Juan Capistrano, California) followed by separate maturation procedures. Primary endpoints were brachial artery flow volume ≥ 500 mL/min and target vein diameter ≥ 4 mm in > 49% of patients and absence of device-related complications at 90 days. RESULTS: AVFs with fused anastomoses were created in 95% (102/107) of patients. Maturation procedures included anastomotic balloon dilation in 72% (77/107), brachial vein embolization in 32% (34/107), cubital vein ligation in 31% (33/107), and surgical transposition in 26% (28/107) of patients. Primary flow and diameter endpoints were achieved in 86.0% (92/107) of patients, exceeding performance goal of 49% (P < .0001). No major adverse events were attributed to the device. Cumulative patency was 91.6%, 89.3%, and 86.7% at 90 days, 180 days, and 360 days. Target dialysis veins were cephalic, basilic, and brachial veins in 74% (73/99), 24% (24/99), and 2% (2/99) of patients. Two-needle dialysis was achieved in 88% (71/81) of patients on hemodialysis at a mean 114.3 days ± 66.2. Functional patency was 98.4%, 98.4%, and 92.3% at 90 days, 180 days, and 360 days. CONCLUSIONS: The Ellipsys® Vascular Access System met primary safety and efficacy endpoint goals in the US pivotal trial.

Expression, Purification, and Properties of a Human Arachidonoyl-Specific Isoform of Diacylglycerol Kinase.

Diacylglycerol kinase ε (DGKε) catalyzes the phosphorylation of diacylglycerol, producing phosphatidic acid. DGKε demonstrates exquisite specificity for the acyl chains of diacylglycerol. This contributes to the enrichment of particular acyl chains within the lipids of the phosphatidylinositol cycle. Phosphatidylinositol is highly enriched with 1-stearoyl-2-arachidonoyl, which is important for maintaining cellular health. Dysregulation of DGKε perturbs lipid signaling and biosynthesis, which has been linked to epilepsy, Huntington's disease, and heart disease. Recessive loss-of-function mutations in the DGKε gene cause atypical hemolytic uremic syndrome. Because DGKε has never been purified, little is known about its molecular properties. We expressed human DGKε and a truncated version lacking the first 40 residues (DGKεΔ40) and purified both proteins to near homogeneity using nickel affinity chromatography. Kinase activity measurements showed that both purified constructs retained their acyl chain specificity for diacylglycerol with an activity level comparable to that of N-terminally FLAG epitope-tagged forms of these proteins expressed in COS7 cells. Both constructs lost activity upon being stored, particularly upon freezing and thawing, which was minimized by the addition of glycerol. Circular dichroism revealed that DGKε and DGKεΔ40 both contain significant amounts of α-helical and ß structure and exhibit biphasic thermal denaturations. The loss of secondary structure upon heating was irreversible for both constructs, with relatively little effect of added dioleoylphosphatidylcholine. The addition of 50% glycerol stabilized both constructs and facilitated refolding of their secondary structures after heating. This is the first successful purification and characterization of DGKε's enzymatic and conformational properties. The purification of DGKε permits detailed analyses of this unique enzyme and will improve our understanding of DGKε-related diseases.

Basilic elevation transposition may improve the clinical outcomes for superficialization of basilic arteriovenous fistula veins.

OBJECTIVE: Basilic vein arteriovenous fistulas are an important and common option for hemodialysis access and require superficialization before use. Various superficialization techniques have been employed, such as basilic tunnel transposition (BTT), basilic elevation, and basilic elevation transposition (BET). Each technique may have advantages and disadvantages, and there have been few reports directly comparing the outcomes of these techniques. This report compares the clinical outcomes of BET vs BTT performed by a single operator and discusses some technical considerations derived from this study and the literature. METHODS: The demographic and outcome data of patients who underwent second-stage basilic vein transposition at an ambulatory surgery center from February 2009 to January 2016 were collected and analyzed. RESULTS: Of the 99 patients identified, 53% were male and 64% were diabetic; the mean age was 61 ± 16 years; 27 had BTT and 72 had BET; the mean follow-up was 26.2 ± 20.5 (range, 1-83) months. The primary patency, assisted primary patency, and secondary patency rates of the whole fistula conduit were 26%, 91%, and 100% for the BTT group and 46%, 98%, 100% for the BET group at 1 year and 21%, 80%, 94% for the BTT group and 38%, 98%, 98% for the BET group at 2 years. The primary patency rate of the basilic vein (segment of the fistula conduit superficialized by transposition) at 1 year was significantly lower for the BTT group vs the BET group (26% vs 61%; P = .004). The average number of percutaneous interventions required for the basilic vein was significantly more for the BTT group vs the BET group (1.5 ± 1.3 vs 0.6 ± 1.0/access-year; P = .007). Based on a Cox regression analysis, the surgical techniques were the only clinical factor that significantly affected the basilic vein primary patency (hazard ratio of 2.28 in favor of BET over BTT; 95% confidence interval, 1.25-4.14; P = .007). CONCLUSIONS: BET is a reliable approach that yields a high cumulative fistula survival rate. Compared with BTT, BET is associated with improved basilic vein primary patency and reduced need for endovascular interventions.

Treatment of High Flow Arteriovenous Fistulas after Successful Renal Transplant Using a Simple Precision Banding Technique.

BACKGROUND: Observation versus ligation of a functional arteriovenous fistula (AVF) after successful renal transplantation (SRT) has been a controversial topic of debate. Congestive heart failure and pulmonary hypertension are common in dialysis patients, and more frequent when vascular access flow is excessive. Renal transplant failure may occur in up to 34% of patients after 5 years, therefore maintaining a moderate flow AVF appears warranted. We review SRT patients with high flow-AVFs (HF-AVF) and clinical signs of heart failure where a modified precision banding procedure was used for access flow reduction. METHODS: Patients referred for HF-AVF evaluation after SRT were identified and records reviewed retrospectively. In addition to recording clinical signs of heart failure, each patient had ultrasound AVF flow measurement before and after temporary AVF occlusion of the access by digital compression. Pulse rate and the presence or absence of a cardiac murmur was noted before and after AVF compression. Adequacy of access flow restriction was evaluated intraoperatively using ultrasound flow measurements, adjusting the banding diameter in 0.5 mm increments to achieve the targeted AVF flow. RESULTS: Twelve patients were evaluated over a 19-month period. Eight (66%) were male and one (8%) obese. Ages were 15-73 years (mean = 42). The AVFs were established 24-86 months previously. The mean pulse rate declined after AVF compression from 90/min to 72/min (range 110-78). Six patients had a precompression cardiac flow murmur that disappeared with temporary AVF compression. One patient with poor cardiac function underwent immediate AVF ligation with dramatic improvement in cardiac status. All other patients underwent a precision banding procedure with real-time flow monitoring. Mean access flow was 2,280 mL/min (1,148-3,320 mL/min) before access banding and was 598 mL/min (481-876) after flow reduction. The clinical signs of heart failure disappeared in all patients. All AVFs remained patent although one individual later requested ligation for cosmesis. Two patients had renal transplant failure and later successfully used the AVF. Follow-up postbanding was 1-18 months (mean = 12). CONCLUSIONS: Patients with successful renal transplants and HF-AVFs had resolution of heart failure findings and maintenance of access patency using a modified precision banding procedure. Flow reduction in symptomatic renal transplant patients with elevated access flow is recommended. Further study is warranted to substantiate these recommendations and clarify the appropriate thresholds for such interventions.

Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry.

The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR) signaling through molecular mimicry. The TIR domain-containing protein TcpB from Brucella inhibits TLR signaling through interaction with host adaptor proteins TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we have determined the X-ray crystal structures of the TIR domains from the Brucella protein TcpB and the host adaptor protein TIRAP. We have further characterized homotypic interactions of TcpB using hydrogen/deuterium exchange mass spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation and NF-κB reporter assays. The crystal structure of the TcpB TIR domain reveals the microtubule-binding site encompassing the BB loop as well as a symmetrical dimer mediated by the DD and EE loops. This dimerization interface is validated by peptide mapping through hydrogen/deuterium exchange mass spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N-terminal TIR domain fold containing a disulfide bond formed by Cys(89) and Cys(134). A comparison between the TcpB and TIRAP crystal structures reveals substantial conformational differences in the region that encompasses the BB loop. These findings underscore the similarities and differences in the molecular features found in the microbial and host TIR domains, which suggests mechanisms of bacterial mimicry of host signaling adaptor proteins, such as TIRAP.