NEXUS Arch: A Multicenter Study Evaluating the Initial Experience With a Novel Aortic Arch Stent Graft System.

OBJECTIVE: To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. SUMMARY BACKGROUND DATA: The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. METHODS: Patients underwent transcatheter aortic arch repair with a single branch, 2 stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the 2 stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk, and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid-carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through 1 year. Survival analysis used the Kaplan-Meier method. RESULTS: Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients, while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5 (17.8%) had combined or other pathologies. At 1 month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all nondisabling), and combined mortality/stroke rate was 10.7%. One-year mortality was 10.7%, without device or aneurysm-related death. Two patients (7.1%) reported stroke or transient ischemic attack at 1 year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were 3 patients (10.7%) that had device-related unplanned reinterventions through 1 year. CONCLUSIONS: The NEXUS Aortic Arch Stent Graft System, a novel single branch, 2 stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent 1 year safety and performance.

Minimally invasive bail-out transthoracic coiling of giant cardiac pseudoaneurysm with good long-term result.

BACKGROUND: We report a case of successful minimally invasive transthoracic coiling of a left ventricle pseudoaneurysm after iatrogenic cardiac perforation with a good long-term result. The pseudoaneurysm could be repaired neither by an open surgery because of poor general state of the patient nor interventionally because of a partial sealing with an Amplatzer Septal Occluder blocking the tight neck of the aneurysm. METHODS AND RESULTS: We performed a transthoracic coiling of the left ventricle pseudoaneurysm using a direct ultrasound-guided puncture via intercostal access below the lingula. The access puncture was performed during a single lung apnea at the end of an expiration phase with a contralateral single lung ventilation. The patient successfully recovered and has been followed-up during the 5 years. CONCLUSIONS: Transthoracic coil embolization is a minimally invasive treatment option for otherwise inoperable patients with cardiac pseudoaneurysms with good long-term results.

Improved technique for sheath supported contralateral limb gate cannulation in endovascular abdominal aortic aneurysm repair.

Background: To present a technique of sheath supported contralateral limb gate (CLG) cannulation of modular bifurcated stent-graft in endovascular abdominal aortic repair. Materials and methods: After totally percutaneous bilateral femoral access, the 9F introducer sheath is exchanged to a 30 cm 12 fr introducer sheath over a stiff wire contralateral to the intended main stent-graft insertion side and advanced into the aorta below the lowest renal artery. Parallel to the stiff wire within the sheath an additional standard J-tip guidewire with a 5 fr Pigtail angiographic catheter is advanced to the level of the renal arteries. After main body deployment, the 12 fr introducer sheath and J-tip wire with pigtail catheter are retracted until the CLG opening level, maintaining the stiff "buddy" wire in position to support the 12 fr sheath, maintaining its distal opening close to the contralateral gate opening to achieve easy cannulation. Results: Retrospective analysis of video archive from July 2016 to February 2018 evidenced 55 recorded EVAR cases. All CLG cannulations were obtained with Standard J-tip or Terumo Glidewire wires and with Pig-Tail or Berenstein catheters. Technical success was 100 %. Mean fluoroscopy time to accomplish CLG cannulation was 37.6 33 (range 1-105) seconds. The aortic carrefour angulation on coronal axis strongly correlates with cannulation time p = <.001, with longer cannulation time for higher carrefour angulations on coronal axis (Pearson correlation coefficient 0.47). Conclusions: The use of 12 fr sheath with parallel wire introduction technique, appears to be a safe and reliable tool to facilitate CLG cannulation during EVAR procedures.

Patient-Specific Rehearsal Feasibility Before Endovascular Repair of Ruptured Abdominal Aortic Aneurysm.

Purpose: To evaluate the feasibility of a patient-specific rehearsal (PsR) before emergency endovascular aneurysm repairs (eEVAR) and its influence on the operation. Materials and Methods: From February 2016 to October 2016, 10 consecutive patients (mean age 75±7.4 years; 9 men) presenting with a ruptured abdominal aortic aneurysm (rAAA) suitable for standard EVAR were enrolled in the study. A 3-dimensional (3D) model of the abdominal aorta was generated on a virtual reality simulator based on the patient's computed tomography (CT) images. Following the patient-specific simulation setup, PsR was conducted during patient admission or in parallel with the preoperative eEVAR workup. Measured outcomes were PsR feasibility only in the first 4 patients and impact on operative performance thereafter (changes in device selection, the planning process, clinical outcomes, perioperative mortality, and complication rates). Technical metrics and timing of system setup, rehearsal, interval from patient arrival to the actual procedure, and eEVAR were recorded. Results: Mean time for 3D model creation was 21.3±7.8 minutes (range 13-37); there was a significant positive relationship between aortic neck diameter and segmentation time (p=0.003). The overall mean time for simulator setup and PsR was 54±14 minutes (range 37-80); PsR alone was completed in a mean 31±40 minutes (95% confidence interval -60 to -2.2). The actual eEVAR procedure duration was 69±16 minutes (range 45-90). No delay in the actual eEVAR procedure was registered owing to the PsR pathway. In 6 patients, preprocedure rehearsal induced changes in operative strategy, including device selection, main body introduction side, and/or deployment configuration. In 4 cases, rehearsal was performed twice to achieve optimal performance. Conclusion: PsR before eEVAR was feasible in all cases and caused no time delays in the actual eEVAR procedure. PsR optimized eEVAR planning by identifying optimal strategy for stent-graft component selection and deployment.

Tubular Cytoplasmic Expression of Zinc Finger Protein SNAI1 in Renal Transplant Biopsies: A Sign of Diseased Epithelial Phenotype?

The aim of the present study was to analyze in vivo the role of zinc finger protein SNAI1 (SNAI1) on renal fibrosis. Unilateral ureteral obstruction injury was induced in Snai1 knockout mice. Snai1 gene deletion was, however, only partial and could therefore not be correlated to reduced fibrosis. Expression of SNAI1 protein and epithelial-mesenchymal transformation markers was then assessed in human chronic allograft nephropathy biopsy specimens. Significant up-regulation of SNAI1 protein was detected within cytoplasm of proximal tubules localized, for some of them, near foci of fibrosis and tubular atrophy. No concomitant epithelial-mesenchymal transformation could, however, be demonstrated analyzing the expression of the fibroblast markers vimentin, α-smooth muscle actin, and S100A4. SNAI1 cytoplasmic up-regulation was particularly evident in biopsy specimens obtained from calcineurin inhibitor-treated patients, which might be because of, as suggested by in vitro experiments, a decrease of the proteasome chimotrypsin activity. Deeper analysis on chronic allograft nephropathy biopsy specimens suggested that SNAI1 cytoplasmic up-regulation was preceded by a transient increase of phosphorylated heat shock protein 27, p38 mitogen-activated protein kinase, and glycogen synthase kinase 3ß. Concomitant down-regulation of the polyubuquitinylated conjugates was detected in SNAI1+ tubules. Altogether, these results might suggest that calcineurin inhibitor-induced tubular SNAI1 protein cytoplasmic accumulation, possibly because of impaired SNAI1 proteasomal degradation and nuclear translocation, might be a sign of a diseased profibrotic epithelial phenotype.

Early outcomes with a single-sided access endovascular stent.

OBJECTIVE: The objective of this study was to report the 1-year follow-up study results of the new Horizon stent graft (Endospan, Herzliya, Israel) from two different prospective consecutive trials. The Horizon abdominal aortic aneurysm stent graft system is a 14F profile system requiring only a single access site. It consists of three modules, introduced separately: base limb (iliac to iliac limb); distal aortic limb; and proximal aortic limb with a bare suprarenal crown and active fixation. METHODS: Data from the first in man (FIM) clinical study with 10 patients enrolled and the pivotal study with 30 patients were analyzed. Outcomes measured were freedom from major adverse events (MAEs) including all-cause mortality, myocardial infarction, renal failure, respiratory failure, paraplegia, stroke, bowel ischemia, and procedural blood loss ≥1000 mL. Performance end points included successful delivery and deployment of the device, freedom from aneurysm growth ≥5 mm, type I or type III endoleak, stent graft occlusion, conversion to open surgery, rupture, and stent graft migration. RESULTS: In the FIM study, one conversion to open surgery with >1000 mL of blood loss was registered perioperatively. In the pivotal study, no perioperative MAE was registered. Overall, at 1-year follow-up, two deaths and one aneurysm growth unrelated to endoleak were registered. CONCLUSIONS: The results of both the FIM and pivotal studies demonstrated that 39 of 40 procedures were successful for delivery and deployment of the Horizon stent graft. No MAE was registered during the follow-up. The primary safety and performance end points were met in both studies.

The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy.

Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo. The urine albumin-to-creatinine ratio was significantly decreased by 66% with linagliptin and 92% with telmisartan versus placebo. Blood pressure was significantly lowered by telmisartan, but it was not affected by linagliptin. As shown by mass spectrometry, the number of altered peptide signals for linagliptin in plasma was 552 and 320 in the kidney. For telmisartan, there were 108 peptide changes in plasma and 363 in the kidney versus placebo. Linagliptin up-regulated peptides derived from collagen type I, apolipoprotein C1, and heterogeneous nuclear ribonucleoproteins A2/B1, a potential downstream target of atrial natriuretic peptide, whereas telmisartan up-regulated angiotensin II. A second study was conducted to confirm these findings in 5/6 nephrectomy wild-type and genetically deficient DPP-4 rats treated with linagliptin or placebo. Linagliptin therapy in wild-type rats was as effective as DPP-4 genetic deficiency in terms of albuminuria reduction. Thus, linagliptin showed comparable efficacy to telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. However, the underlying pathways seem to be different.

The Gore Hybrid Vascular Graft in renovisceral debranching for complex aortic aneurysm repair.

OBJECTIVE: This study reports our initial experience with the Gore Hybrid Vascular Graft (GHVG; W. L. Gore & Associates, Flagstaff, Ariz) for staged hybrid open renovisceral debranching and endovascular aneurysm repair in patients affected by thoracoabdominal aortic aneurysms and pararenal abdominal aortic aneurysms (PAAAs). METHODS: Between December 2012 and December 2013, we analyzed outcomes of 13 patients who underwent open surgical debranching of renovisceral vessels for thoracoabdominal aortic aneurysm and PAAAs. All patients were considered at high risk for conventional surgery. Inclusion criterion was treatment by open surgical debranching of at least one visceral artery (renal artery, superior mesenteric artery [SMA], or celiac trunk [CT]) using the GHVG. In a second step, the aortic stent graft was implanted to exclude the aneurysm. If required, parallel grafts to the remaining visceral arteries were deployed in the same procedure. One patient had a symptomatic descending thoracic aortic aneurysm and another had a ruptured PAAA. Perioperative measured outcomes were immediate technical success rate, mortality, and morbidity. Median follow-up was 24.8 months (range, 0-15; mean, 8.2; standard deviation, 4 months). RESULTS: All open surgical debranching of renovisceral vessels were completed as intended. GHVG was used to revascularize 20 visceral vessels in 13 patients with a mean of 1.54 vessels per patient. Six renal arteries (30%; 2 right and 4 left), 9 SMAs (45%), and 5 CTs (25%) were debranched. In nine of 13 (66%) patients, other renovisceral arteries were addressed with chimney/periscope, Viabahn Open Revascularization Technique, and end-to-side anastomosis. Two of 13 patients (15%) died of bowel ischemia. Neither patient had GHVG revascularization to the SMA or CT. Perioperative complications occurred in three patients (23%; 1 renal hematoma, 1 respiratory insufficiency, and 1 small-bowel ischemia related to a SMA GHVG thrombosis). At 24 months, estimated survival was 85%, and estimated primary and secondary patency were 94% and 100%, respectively. CONCLUSIONS: This limited series extracted from a more consistent hybrid procedure experience showed a mortality rate similar to most recent reports. Technical feasibility and the short-term patency rate of the GHVG for renovisceral debranching during staged hybrid open and endovascular procedures were satisfactory. Use of GHVGs may represent a useful revascularization adjunct to minimize visceral ischemia in these challenging patients.

Long-term results of simplified frozen elephant trunk technique in complicated acute type A aortic dissection: A case-control study.

AIM: To describe the long-term experience of a simplified frozen elephant trunk technique (sFETT) used in complicated acute type A aortic dissection (AAAD) treatment. METHODS AND RESULTS: Between January 2001 and December 2012, 34 patients (mean age 59.9 ± 11.0 years) with complicated AAAD (DeBakey I) underwent an emergency surgery including sFETT. sFETT consisted in gluing the dissected aortic arch wall layers with gelatine-resorcinol adhesive and video-assisted antegrade open arch aortic stent-graft deployment in the arch or proximal descending aorta. In addition to sFETT, the aortic root was addressed with standard techniques. A 30-day mortality was 14.7% (five patients) due to bleeding (1), multiple organ failure (2), and colon ischemia (2). Postoperative morbidity included neurological (2), renal (1) and cardio-pulmonary complications (4), as well as wound infection (1). Mean follow-up was 74.4 ± 45.0 months. Actual survival rates were 73.5% at 1 year, 70.2% at 5 years, and 58.5% at 13 years of follow-up. Six patients died during long-term follow-up from heart failure (1) and unknown reasons (5). Five patients required reoperation for aortic arch (3) or aorto-iliac (2) progression of aneurysm during the mid- and long-term follow-up. The remaining patients showed favorable evolution of the dissected aorta with false lumen occlusion in most cases and stable aortic diameters. CONCLUSIONS: In AAAD patients, sFETT as used in our series is an easy and safe technique to repair the aortic arch. Long-term results after sFETT showed false lumen occlusion and stable aortic diameter in up to 13 years of follow-up.

Endothelin-1 Overexpression Improves Renal Function in eNOS Knockout Mice.

BACKGROUND/AIMS: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. METHODS: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. RESULTS: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpine1, TIMP1, Col1a1, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. CONCLUSION: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in ß-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels).

A 12-Year Experience With Chimney and Periscope Grafts for Treatment of Type I Endoleaks.

PURPOSE: To evaluate the midterm outcomes of chimney and/or periscope grafts (CPGs) in patients presenting type I endoleak after a previous endovascular aneurysm repair (EVAR). METHODS: Between June 2002 and April 2014, 24 consecutive patients (mean age 73.9±9.2 years; 23 men) presenting a type I endoleak were addressed with CPGs to extend the proximal and/or distal landing zone and to maintain side branch perfusion. Indication for treatment was a type Ia endoleak in 23 (96%) patients and a type Ib endoleak in one. Median interval from the previous EVAR to endoleak treatment with CPGs was 52.2±48.9 months (range 0.2-179). All patients had proximal/distal landing zones precluding any standard endovascular reintervention. Measured outcomes included technical success and perioperative mortality and morbidity. Technical success was defined as a procedure completed as intended, with no secondary procedures within 30 days. Midterm outcomes included survival, CPG patency, endoleaks, and freedom from reintervention. RESULTS: Technical success was 96%; a single patient required an additional procedure to seal a recurrent type Ia endoleak. Intraoperative revascularization of all 55 target vessels (2.3/patient) with CPGs was successful. One (4%) patient died within 30 days. Estimated survival at 12, 24, and 36 months was 83%; estimated CPG patency at the same intervals was 94%. Over a mean follow-up of 23.4±29 months, 6 (25%) reinterventions were performed; of these, 4 were secondary to type I endoleak. Aneurysm diameters reduced from 88.3±26 to 85.5±33 mm (p=0.49) over the mean follow-up. CONCLUSION: The CPG technique is a safe and effective tool for treatment of type I endoleak after previous EVAR. The CPG technique is feasible even in nonelective patients, with excellent outcomes in terms of patency. Close imaging follow-up is warranted to rule out recurrent or de novo endoleaks.

Development and validation of a macroarray system--MutaCHIP ARTERO--for the detection of genetic variants involved in the pathogenesis of atherosclerosis.

BACKGROUND: Cardiovascular diseases are the leading cause of death in developed countries. The underlying mechanism is often atherosclerotic remodeling of blood vessels in organs such as heart, kidney, brain, and large arteries in case of peripheral arterial disease. Beside environmental and behavioral factors such as smoking or lack of physical activity, genetic variants in genes involved in lipid metabolism, blood pressure regulation, oxidative stress, and coagulation play a prominent role in the pathogenesis of atherosclerosis. METHODS: Thus, we developed and validated for clinical use and research a macroarray system for the simultaneous detection of key genetic variants in genes involved in lipid metabolism, blood pressure regulation, oxidative stress, and coagulation. RESULTS: When compared with standard PCR technologies to determine all these genetic variants in parallel, the macroarray system (MutaCHIP ARTERO) was as accurate but faster, cheaper, and easier to handle compared to classical real time PCR based technologies. CONCLUSIONS: MutaCHIP ARTERO is a gene chip for diagnostics of a complex genetic panel involved in the pathogenesis of atherosclerosis. This method is as sensitive and precise as real time PCR and is able to replicate real time PCR data previously validated in evaluation studies.

A hybrid open and endovascular repair for treatment of bovine aortic arch aneurysm accompanied by aneurysm of patent ductus arteriosus with deployment of Amplatzer duct occluder.

A rare case of bovine aortic arch aneurysm accompanied by patent ductus Botalli aneurysm was treated using an off-pump hybrid procedure including supraaortic debranching combined with aortic stent grafting and oversewing of pulmonary artery end of the aneurysm. Postoperative computed tomography angiography showed persistent perfusion of the ductus Botalli aneurysm from pulmonary artery, which was successfully closed with an Amplatzer duct occluder. Twenty-two months of follow-up showed good general state of the patient's health status. This less invasive procedure is an alternative to aortic replacement under circulatory arrest and may be the only salvage option for patients in poor general condition.

Paraincisional subcutaneous infusion of ropivacaine after open abdominal vascular surgery shows significant advantages.

BACKGROUND: Opiates are widely used for postoperative pain relief. Unfortunately, their side effects such as inhibited gastrointestinal motility and respiratory depression may compromise or delay postoperative recovery after laparotomy. We used paraincisional subcutaneous catheters (PSCs) and applied 0.25% ropivacaine infusion to improve pain relief and decrease postoperative morphine consumption in patients after open surgery for aortic aneurysm. METHODS: A retrospective single-center study including 58 patients treated by open surgery for aortic aneurysm between October 2006 and June 2012. Overall, 28 patients (control group) received standard postoperative pain management including opiates, and 30 patients (PSC group) were treated with paraincisional continuous local analgesia with 0.25% ropivacaine administrated via bilateral subcutaneous catheters along with additional ad libitum opiates administration, at first intravenously and then orally. RESULTS: Patients characteristics as well as perioperative and postoperative outcomes were comparable between the groups during the first 5 days after surgery. Patients of the PSC group received significantly less morphine, although the patients in both groups reported a similar pain intensity. Neither wound-healing disorder nor catheter-associated subcutaneous infection was reported. High serum concentration of ropivacaine was detected in 2 patients (6%) with end-stage renal disease, who developed temporary neurologic symptoms. Length of intensive care unit (ICU) stay was significantly shorter in the PSC group (2 [0-23] vs. 4.5 [0-32] ICU days). CONCLUSIONS: This is the first report about PSCs for analgesia after laparotomy. This case/control study shows that continuous paraincisional subcutaneous infusion of 0.25% ropivacaine after open surgery for aortic aneurysm repair is a feasible method of postoperative analgesia. This technique allows sustained pain relief with significant reduction of opiate requirement and faster recovery after surgery. Prospective randomized controlled trial is necessary for the assessment of safety and efficacy of this method.

Long-term outcomes of living donor kidney transplants in pediatric recipients following laparoscopic vs. open donor nephrectomy.

We compared long-term outcomes of LDKT in pediatric recipients following either laparoscopic (LDN) or ODN. In our retrospective single-center study, we compared 38 pediatric LDKT recipients of a laparoscopically procured kidney with a historic ODN group comprising 17 pediatric recipients. In our center, the first pure laparoscopic non-hand-assisted LDN for a pediatric LDKT recipient was performed in June 2001. Demographic data of donors and recipients were comparable between groups. Mean follow-up was 64 months in the LDN group and 137 months in the ODN group. Patient survival was comparable between groups. Graft survival at one and five yr was 97% (LDN) vs. 94% (ODN) and 91% (LDN) vs. 88% (ODN; p = n.s.), respectively. Serum creatinine at one and five yr was 1.16 ± 0.47 mg/dL (LDN) vs. 1.02 ± 0.38 mg/dL (ODN) and 1.38 ± 0.5 mg/dL (LDN) vs. 1.20 ± 0.41 mg/dL (ODN), respectively. The type and frequency of surgical complications did not differ between groups. DGF and acute rejection rates were similar between groups. In the ODN group, a higher proportion of right donor kidneys was used. In the ODN group, all kidneys had singular arteries, whereas in the LDN group five kidneys had multiple arteries. Arterial multiplicity was associated with a higher incidence of DGF. In our experience, LDN does not compromise long-term graft outcomes in pediatric LDKT recipients. Arterial multiplicity of the donor kidney may be a risk factor for impaired early graft function in the pediatric population.

Quantitative and qualitative evaluation of liver metastases with intraprocedural cone beam CT prior to transarterial radioembolization as a predictor of treatment response.

Purpose: To investigate, by quantitative and qualitative enhancement measurements, the correlation between tumor enhancement on cone beam computed tomography (CBCT) images and treatment response at 6 months in patients undergoing transarterial radioembolization (TARE) for liver metastases. Materials and Methods: 36 patients (56% male; median age 62.5 years) with 104 metastases were retrospectively included. Quantitative and qualitative enhancement of liver metastases were evaluated on CBCT images before TARE. Quantitative analysis consisted of lesion enhancement measurements (ROI HU lesion - ROI HU relative to inferior vena cava). Qualitative analysis consisted of subjective enhancement pattern analysis (diffuse, sparse, rim-like or non-enhancing). Morphologic tumor response was evaluated according to RECIST 1.1 criteria on follow-up CT or MR imaging. Results: At a mean follow up of 6.5 ± 3.7 months, progressive disease (PD) was found in 4 patients, partial response (PR) in 11 and stable disease (SD) in 21. Relative lesion enhancement was significantly different between these groups (-37.5±154.2 HU vs. 103.8±93.4 vs. 181±144 HU in PD vs. SD vs. PR group, respectively; p<0.01). ROC analysis of relative lesion enhancement to predict progressive disease showed an area under the curve of 0.86 (p<0.01). For qualitative lesion enhancement analysis, no difference between groups was found. Conclusion: Quantitative enhancement measurements derived from intraprocedural contrast enhanced CBCT may identify responders to TARE in patients with liver metastases.

Head-to-Head Comparison of Oxidative Stress Biomarkers for All-Cause Mortality in Hemodialysis Patients.

Oxidative stress (OS) presents even in the early chronic kidney disease (CKD) stage and is exacerbated in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD). There is still a debate over the association between oxidative stress and mortality. Our study aims to compare head-to-head the prognostic value of different oxidative markers for all-cause mortality in hemodialysis (HD) patients. We thus enrolled 347 patients on HD in this prospective study. Four OS biomarkers were measured (carbonyl proteins, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), and oxidized low-density lipoprotein (ox-LDL)). During the 60-month follow-up period, 9 patients have been lost to follow-up and 168 (48.4%) patients died. Concerning the oxidative stress (ox-stress) byproducts, carbonyl proteins were lower in survivors (105.40 ng/mL (IQR 81.30−147.85) versus 129.65 ng/mL (IQR 93.20−180.33); p < 0.001), with similar results for male patients (103.70 ng/mL (IQR 76.90−153.33) versus 134.55 ng/mL (IQR 93.95−178.68); p = 0.0014). However, there are no significant differences in MPO, AOPP, and ox-LDL between the two groups. Kaplan−Meier survival analysis indicated that patients in the higher carbonyl proteins concentration (>117.85 ng/mL group) had a significantly lower survival rate (log-rank test, p < 0.001). Univariate Cox regression analysis showed a positive correlation between carbonyl proteins and all-cause mortality in the higher and lower halves. Even after adjustment for conventional risk factors, it remained a statistically significant predictor of an increased risk of death in MHD. Univariate Cox regression analysis of MPO showed that continuous MPO and Log MPO were significantly associated with all-cause mortality, except for binary MPO (divided according to the median of MPO). Multivariate Cox analysis for MPO showed that the mortality prediction remains significant after adjusting for multiple factors. In conclusion, not all ox-stress biomarkers predict all-cause mortality in HD patients to a similar extent. In the present study, carbonyl proteins and MPO are independent predictors of all-cause mortality in HD patients, whereas AOPPs and oxLDL are clearly not associated with all-cause mortality in HD patients.

Three-year follow-up of aortic arch endovascular stent grafting with the Nexus device: results from a prospective multicentre study.

OBJECTIVES: Endovascular aortic arch stent grafting with branched devices has shown initial promising results. The aim of this prospective, multicentre study was to evaluate 3-year outcomes of aortic arch stent grafting with NEXUS® Aortic Arch Stent Graft System (Nexus), a single-branch, bi-modular, off-the-shelf aortic arch stent graft system in high-risk patients. METHODS: Patients treated with Nexus, either under the feasibility clinical study or as compassionate use procedures in 5 centres, were included in this study. The primary end point was overall survival. The secondary end points included the incidence of procedure-related unplanned intervention, stroke, paraplegia and endoleak. Clinical and radiologic follow-up was performed at each study site at 30 days, 6 months and on a yearly basis thereafter up to 3 years postoperatively. RESULTS: We analysed data from a total of 28 patients. The overall median follow-up was 1132 (interquartile range: 809-1537). There were no device or procedure-related deaths between 1 and 3 years. Overall survival at 1 and 3 years was 89% and 71%, respectively. The cumulative incidence of unplanned reintervention at 1 and 3 years was 11% and 29%, respectively. There were no reports of stroke, paraplegia, aneurysm rupture, myocardial infarction or new aortic valve insufficiency. In this study's 1-3 year follow-up period, 1 type Ib (4%), 1 type II (4%) and 2 type III (8%; between Nexus' distal end and Thoracic endovascular aortic repair (TEVAR) extensions) endoleak were detected. CONCLUSIONS: Endovascular aortic arch exclusion with the single-branch, off-the-shelf Nexus system provides promising clinical and radiologic results at 3-year follow-up in a high-risk patient cohort.

Inhibition of 20-HETE synthesis and action protects the kidney from ischemia/reperfusion injury.

20-Hydroxyeicosatetraenoic acid (20-HETE) production is increased in ischemic kidney tissue and may contribute to ischemia/reperfusion (I/R) injury by mediating vasoconstriction and inflammation. To test this hypothesis, uninephrectomized male Lewis rats were exposed to warm ischemia following pretreatment with either an inhibitor of 20-HETE synthesis (HET0016), an antagonist (20-hydroxyeicosa-6(Z),15(Z)-dienoic acid), an agonist (20-hydroxyeicosa-5(Z),14(Z)-dienoic acid), or vehicle via the renal artery and the kidneys were examined 2 days after reperfusion. Pretreatment with either the inhibitor or the antagonist attenuated I/R-induced renal dysfunction as shown by improved creatinine clearance and decreased plasma urea levels, compared to controls. The inhibitor and antagonist also markedly reduced tubular lesion scores, inflammatory cell infiltration, and tubular epithelial cell apoptosis. Administering the antagonist accelerated the recovery of medullary perfusion, as well as renal medullary and cortical re-oxygenation, during the early reperfusion phase. In contrast, the agonist did not improve renal injury and reversed the beneficial effect of the inhibitor. Thus, 20-HETE generation and its action mediated kidney injury due to I/R. Whether or not these effects are clinically important will need to be tested in appropriate human studies.

Biomarkers for the prediction of mortality and morbidity in patients with renal replacement therapy.

The mortality of end-stage renal disease (ESRD) patients on dialysis remains high despite great improvement of dialysis technologies in the past decades. These patients die due to infectious diseases (mainly sepsis), cardiovascular diseases such as myocardial infarction, heart failure, stroke, and, in particular, sudden cardiac death. End stage renal disease is a complex condition, where the failure of kidney function is accompanied by numerous metabolic changes affecting almost all organ systems of the human body. Many of the biomarker characteristics of the individually affected organ systems have been associated with adverse outcomes. These biomarkers are different in patients with ESRD compared to the general population in the prediction of morbidity and mortality. Biomarker research in this field should aim to identify patients at risk for the different disease entities. Traditional biomarkers such as CRP, BNP, and troponins as well as new biomarkers such as fetuin, CD154, and relaxin were analyzed in patients on dialysis. We will include observational as well as prospective clinical trials in this review. Furthermore, we will also discuss proteomics biomarker studies. The article assess the potential diagnostic value of different biomarkers in daily clinical practice as well as their usefulness for clinical drug development in end stage renal disease patients.