Vascular access challenges in hemodialysis patients with superior vena cava syndrome.

BACKGROUND: Superior vena cava syndrome in hemodialysis patients resulting from previous or current use of a tunneled central vein catheter is a rare but potentially severe condition. Two aspects have to be addressed during management and treatment: the restoration of central venous flow and the creation of an alternative vascular access to guarantee hemodialysis. RESEARCH DESIGN: Conforming to the current guidelines and literature, we present a stepwise approach and discuss therapeutic options. The removal of the tunneled central vein catheter should be attempted and a native vascular access created whenever feasible. RESULTS: First, an upper extremity AVF should be preserved or, as in our case, made functional. Endovascular treatment of CVSO should primarily consist of balloon dilatation. Placement of a stent or stent graft should be considered as a secondary option. HeRO graft placement may be considered in recurrent CVSO and recanalization with a Surfacer. LL-AVF or AVG need to be discussed and may be an alternative for certain HD patients when the risk of lower limb ischemia and infection is considered. CONCLUSION: Several therapeutic options are available and the basic principles are well established in the literature, although the level of evidence is not high. Therefore, we propose a stepwise and interdisciplinary approach to guide the challenging decision-making process in SVC.

Endovascular maneuvers for contralateral stent graft limb misplacement in endovascular aortic repair.

Cannulation and placement of the contralateral stent graft limb during endovascular aortic repair (EVAR) procedure are crucial steps as mispositioning may lead to conversion to open aortic repair. Endovascular bail-out strategies for stent graft relocation in EVAR are underreported though detailed knowledge may facilitate application and prevent conversion. We present three endovascular bail-out strategies for repositioning of a mispositioned contralateral stent graft limb. (1) Retraction of the mispositioned component with an inflated reliant balloon and placement of an interposition stent graft after successful cannulation; (2) Push-maneuver of the mispositioned stent graft into the infrarenal aortic aneurysm with an inflated reliant balloon supported by a large lumen introducer sheath and (3) Parallel placement of a second contralateral stent graft limb displacing the mispositioned one against the atrial wall in cases with adequate vessel diameter. Prevention of stent graft mispositioning by applying recognized tests to ensure correct placement are essential, following the slogan: check twice, deploy once.

Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. METHODS AND RESULTS: Among prospectively recruited patients at high cardiovascular risk (age ≥65 years or ≥45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966). CONCLUSION: Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.

A Novel Percutaneous Technique for Aorto-Iliac Thrombectomy without the Risk of Embolization.

Classic surgical thrombectomy of the aorta and iliac arteries through an incision in the groin vessels harbors the risk of embolization to the viscero-renal as well as hypogastric arteries, while percutaneous endovascular thrombectomy techniques can lead to peripheral embolization to the lower limbs. Therefore, we describe a novel, percutaneous technique that tackles the above issues. Furthermore, we also present our initial experience using the technique. The principle of the technique is to percutaneously place large-bore sheaths in the iliac arteries that deliberately occlude the latter to protect the lower limbs from embolization. Through one of these sheaths, over wire Fogarty® catheters can be placed and inflated in the ostia of the coeliac trunk, superior mesenteric artery, renal arteries, and hypogastric arteries as needed. A large thrombectomy balloon catheter is then used to bring any aorto-iliac thrombus into the sheaths, whereafter the thrombus is removed from the sheaths by simply deflating their valves. Additional endovascular procedures of the aorto-iliac branches can be performed as needed. We report nine procedures in 8 patients (4 males and 4 females) with a median age of 63 (53-68.5). Additional endovascular procedures were performed in 6 (66.7%) procedures. All but one procedure were technically successful, and all patients had palpable foot pulses on completion of the procedures, while no patient had clinical signs of peripheral embolization. This technique is a very valid addition to the vascular surgeon's armamentarium when treating aorto-iliac thrombotic events because it is minimally invasive while still protecting against embolization and offering the flexibility to perform a wide range of additional endovascular procedures where needed.

Acute heart failure after non-cardiac surgery: incidence, phenotypes, determinants and outcomes.

AIMS: Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery. METHODS AND RESULTS: A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]). CONCLUSIONS: Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.

Long-term outcomes of perioperative myocardial infarction/injury after non-cardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed. METHODS AND RESULTS: Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into 'extra-cardiac' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and 'cardiac', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis. CONCLUSION: At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments. STUDY REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02573532.

Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation Simulation Training in a Lifelike Flow Model.

Objectives: To assess the feasibility and training effect of simulation training for ultrasound-guided percutaneous arteriovenous fistula (pAVF) creation in a lifelike flow model. Methods: Twenty vascular trainees and specialists were shown an instructional video on creating a pAVF in a dedicated flow model and then randomized to a study or control group. The procedure was divided into five clearly defined steps. Two observers rated the performance on each step, and the time to perform the exercise was recorded. The study group participants underwent supervised hands-on training on the model before performing a second rated pAVF creation. All participants subsequently completed a feedback questionnaire. Results: After supervised simulation training, the study groups participants increased their mean performance rating from 2.2 ± 0.9 to 3.2 ± 0.7. A mean of 3.8 ± 0.8 procedure steps was accomplished independently (control group 2.1 ± 1.4; p < 0.05). The time taken to perform the procedure was 15.6 ± 3.8 min in the study group (control group 27.2 ± 7.3, p < 0.05). The participants with previous experience in ultrasound-guided vascular procedures (n = 5) achieved higher overall mean scores 3.0 ± 0.8 and accomplished more steps without assistance (2.0 ± 1.0) during the simulation training compared to their inexperienced peers (1.5 ± 0.3 and 0.8 ± 0.4, respectively). The feedback questionnaire revealed that the study group participants strongly agreed (n = 7) or agreed (n = 3) that training on the simulation model improved their skills regarding catheter handling. Conclusions: The study group participants increased their overall performance after training on the simulator. More experienced attendees performed better from the beginning, indicating the model to be lifelike and a potential skill assessment tool. Simulation training for pAVF creation using a lifelike model may be an intermediate step between acquiring ultrasound and theoretical pAVF skills and procedure guidance in theatre. However, this type of training is limited by its reliance on the simulator quality, demonstration devices and costs.

Therapeutic arteriogenesis by factor-decorated fibrin matrices promotes wound healing in diabetic mice.

Chronic wounds in type-2 diabetic patients present areas of severe local skin ischemia despite mostly normal blood flow in deeper large arteries. Therefore, restoration of blood perfusion requires the opening of arterial connections from the deep vessels to the superficial skin layer, that is, arteriogenesis. Arteriogenesis is regulated differently from microvascular angiogenesis and is optimally stimulated by high doses of Vascular Endothelial Growth Factor-A (VEGF) together with Platelet-Derived Growth Factor-BB (PDGF-BB). Here we found that fibrin hydrogels decorated with engineered versions of VEGF and PDGF-BB proteins, to ensure protection from degradation and controlled delivery, efficiently accelerated wound closure in diabetic and obese db/db mice, promoting robust microvascular growth and a marked increase in feeding arterioles. Notably, targeting the arteriogenic factors to the intact arterio-venous networks in the dermis around the wound was more effective than the routine treatment of the inflamed wound bed. This approach is readily translatable to a clinical setting.

Cardiovascular imaging following perioperative myocardial infarction/injury.

Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

Patient- and procedure-related factors in the pathophysiology of perioperative myocardial infarction/injury.

BACKGROUND: Perioperative myocardial infarction/injury (PMI) is a frequent, often missed and incompletely understood complication of noncardiac surgery. The aim of this study was to evaluate whether patient- or procedure-related factors are more strongly associated to the development of PMI in patients undergoing repeated noncardiac surgery. METHODS: In this prospective observational study, patient- and procedure-related factors were evaluated for contribution to PMI using: 1) logistic regression modelling with PMI as primary endpoint, 2) evaluation of concordance of PMI occurrence in the first and the second noncardiac surgery (surgery 1 and 2). and 3) the correlation of the extent of cardiomyocyte injury quantified by high-sensitivity cardiac troponin T between surgery 1 and 2. The secondary endpoint was all-cause mortality associated with PMI reoccurrence in surgery 2. RESULTS: Among 784 patients undergoing repeated noncardiac surgery (in total 1'923 surgical procedures), 116 patients (14.8%) experienced PMI during surgery 1. Among these, PMI occurred again in surgery 2 in 35/116 (30.2%) patients. However, the vast majority of patients developing PMI during surgery 2 (96/131, 73.3%) had not developed PMI during surgery 1 (phi-coefficient 0.150, p < 0.001). The correlation between the extent of cardiomyocyte injury occurring during surgery 1 and 2 was 0.153. All-cause mortality following a second PMI in surgery 2 was dependent on time since surgery (adjusted hazard ratio 5.6 within 30 days and 2.4 within 360 days). CONCLUSIONS: In high-risk patients, procedural factors are more strongly associated with occurrence of PMI than patient factors, but patient factors are also contributors to the occurrence of PMI.

A telemedicine communication exchange network in Gorno-Badakhshan Autonomic Oblast in collaboration with Swiss Surgical Teams.

INTRODUCTION: The purpose of this article is to report on the implementation of a telemedicine network serving as a second opinion pool for a surgeon in a remote area of a developing country. METHODS: This study involved an international collaboration between two members of Swiss Surgical Teams at a tertiary referral hospital and a surgeon in a remote area in Gorno-Badakhshan Autonomic Oblast, Tajikistan, which established a second opinion pool discussing diagnostics and therapeutic options via a messenger application. A retrospective analysis of response times was performed using a series of 50 challenging cases. RESULTS: The median time to receive a first telemedical response from any of the two contacts was 24 min (interquartile range 6-73). Urgent and emergent pathologies accounted for 57% of cases. The suggested treatment was carried out in 90% (n = 44) of cases. CONCLUSIONS: Timely and convenient telemedicine support to provide diagnostic and therapeutic reassurance and improve treatment quality for patients presenting to a general and vascular surgeon in the large and remote region of Gorno-Badakhshan Autonomic Oblast can be installed via a messenger application.

Temporary Extracorporeal Femoro-Femoral Crossover Bypass to Treat Acute Limb Ischemia due to Occlusive Femoral Transaortic Microaxial Left Ventricular Assist Device - A Novel Technique and Case Series.

BACKGROUND: The Impella transaortic microaxial left ventricular assist device (MLVAD) bears the risk of severe ipsilateral limb ischemia due to its percutaneous insertion through the common femoral artery (CFA). As long as the MLVAD is required for cardio - circulatory support, treatment options are limited. Therefore, we developed a temporary extracorporeal femoral - femoral crossover bypass to restore and maintain perfusion of the affected leg. METHODS: From October 2018, we treated all patients with severe limb ischemia due to the MLAVD with a femoral - femoral crossover bypass. For comparison, a consecutive cohort of patients undergoing placement of the MLAVD between January 2011 and October 2018 was identified. The primary outcome is the feasibility and safety of our percutaneously established extracorporeal femoral - femoral crossover bypass. RESULTS: Between January 2011 and July 2019, 25 of 245 (10.3%) patients developed a severe ipsilateral limb ischemia following the MLVAD placement. Until October 2018, 20 patients were treated conventionally (C - cohort) and since October 2018, five (consecutive) patients have been treated by an extracorporeal femoral - femoral cross over bypass (BP - Cohort). Following the BP - procedure, an immediate improvement of the perfusion was seen in all patients. Limb salvage was documented in 100% of our patients and 30 - day mortality was 60% in both groups. CONCLUSION: This is the first case series reporting on this novel technique. We demonstrated that the percutaneous creation of an extracorporeal crossover bypass is feasible, safe and effective and should therefore be promoted.

Open aneurysm repair in patients with concomitant abdominal aortic aneurysm and aorto-iliac occlusive disease is associated with a high mortality and surgical complication rate.

AIM OF THE STUDY: To evaluate whether the outcome after open aneurysm repair combined with aorto-femoral bypass in patients with concomitant abdominal aortic aneurysm (AAA) and aorto-iliac occlusive disease (AIOD) is inferior to open aneurysm repair for isolated AAA or aorto-femoral bypass for isolated AIOD. METHODS: We performed a retrospective analysis of 30-day mortality, 1-year mortality and surgical complications of consecutive patients undergoing elective aneurysm repair, aorto-femoral bypass or a combination of these at two vascular surgery departments from 2003 to 2013. Potential risk factors were investigated by multivariable analysis. RESULTS: Overall, 511 patients underwent open repair for isolated AAA, 104 aorto-femoral bypass for isolated AIOD and 46 open AAA repair combined with aorto-femoral bypass for concomitant AAA and AIOD. Surgical complications occurred in 17% of AAA, 23% of AIOD and 37% of combined patients (odds ratio [OR] combined vs AAA 2.76, 95% confidence interval [CI] 1.43-5.34; p = 0.003). Colon ischaemia occurred in 3.7% of AAA, 2.9% of AIOD and 13% of combined patients (incicidence rate ratio [IRR] combined vs AAA 3.27, 95% CI 1.37-7.81; p = 0.01). The 30-day mortality was 3.1% in AAA, 4.8% in AIOD, and 11% in combined patients (IRR combined vs AAA 3.17, 95% CI 1.26-7.96; p = 0.01). One-year mortality was 5.7% in AAA, 5.8% in AIOD and 15% in combined patients (IRR combined vs AAA 2.50, 95% CI 1.17-5.35; p = 0.02). CONCLUSIONS: Combined AAA repair and aorto-femoral bypass has a significantly higher 30-day mortality and postoperative complication rate than isolated AAA repair. Patients with concomitant AAA and AIOD thus represent a high-risk population, which should be considered when deciding on the indication for AAA treatment.

Robust Angiogenesis and Arteriogenesis in the Skin of Diabetic Mice by Transient Delivery of Engineered VEGF and PDGF-BB Proteins in Fibrin Hydrogels.

Non-healing ulcers are a serious complication of diabetes mellitus and a major unmet medical need. A major cause for the lack of healing is the impairment of spontaneous vascularization in the skin, despite mostly normal blood flow in deeper large vessels. Therefore, pro-angiogenic treatments are needed to increase therapeutic perfusion by recruiting new arterial connections (therapeutic arteriogenesis). Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis in physiology and disease, but exploitation of its therapeutic potential requires careful control of its dose distribution in tissue. Co-delivery of platelet derived growth factor-BB (PDGF-BB) has been shown to expand the therapeutic window of VEGF and also improve associated arteriogenesis. We used a highly controlled protein delivery system, based on a clinically applicable fibrin-based platform, to investigate the angiogenic and arteriogenic potential of engineered versions (TG-) of VEGF and PDGF-BB proteins in the skin of diabetic and obese db/db mice. Intradermal delivery of therapeutically relevant doses of TG-VEGF and TG-PDGF-BB induced robust growth of new microvascular networks with similar efficacy as in normal littermate control mice. Further, TG-PDGF-BB prevented the formation of aberrant vascular enlargements by high TG-VEGF levels. As fibrin was degraded after the first week, the induced angiogenesis mostly regressed by 4 weeks, but it promoted effective arteriogenesis in the dermal layer. Therefore, controlled co-delivery of TG-VEGF and TG-PDGF-BB recombinant proteins is effective to induce angiogenesis and arteriogenesis in diabetic mouse skin and should be further investigated to promote diabetic wound healing.

External stenting and disease progression in vein grafts 1 year after open surgical repair of popliteal artery aneurysm.

OBJECTIVE: Open surgical repair remains the gold standard treatment for popliteal artery aneurysms (PAA). The objective of this study was to evaluate the safety of external stenting and its medium-term effect on vein graft disease after open PAA repair. METHODS: Between December 2017 and September 2019, 12 consecutive patients with PAA underwent open surgical repair with externally stented saphenous vein grafts. Duplex ultrasound scanning of the grafts was performed at discharge and at 3, 6, and 12 months after the procedure to evaluate graft patency, average lumen diameter and lumen uniformity. RESULTS: Eleven patients underwent aneurysm ligation and bypass grafting and one patient was treated with aneurysm exclusion and interposition of a venous segment. External stenting of the vein graft was successful in all patients. The mean follow-up time was 12 months (range, 7-17 months), with a primary patency rate of 100% and no graft revisions or reinterventions. The mean lumen diameters at 3, 6, and 12 months were 5.9 ± 1.2 mm, 5.7 ± 0.8 mm, and 5.7 ± 0.7 mm, respectively, with no significant changes between 3 and 6 (P = .34) and between 6 and 12 months (P = .34). The coefficient of variance at 3, 6, and 12 months was 8.2 ± 9.3, 9.4 ± 7.2, and 10.4 ± 8.9, respectively, with no significant change between 3 and 6 months (P = .78) or 6 and 12 months (P = .98). No mortality or amputations were recorded throughout the follow-up period. CONCLUSIONS: External stenting of vein grafts in open surgical repair of PAA is feasible and safe. This technique may potentially improve the outcomes of surgical repair in patients with PAA.

Acute aortic dissection with entry tear at the aortic arch: long-term outcome.

OBJECTIVES: The goal was to evaluate outcomes after conservative or surgical treatment of acute aortic arch dissections. METHODS: Between January 2009 and December 2018, patients with a diagnosis of acute aortic dissection were analysed. Aortic arch aortic dissection was defined as a dissection with an isolated entry tear at the aortic arch with no involvement of the ascending aorta. RESULTS: Aortic arch dissection was diagnosed in 31 patients (age 59 ± 11 years). Surgical intervention was performed in 13 (41.9%) cases. Overall in-hospital mortality was 3% (n = 1), and all deaths occurred in the conservative group (n = 1; 6%), whereas the overall stroke rate was 3% (n = 1), and all strokes occurred in the group treated surgically (n = 1; 8%). Surgical repair was necessary for the following conditions: end-organ malperfusion (n = 9; 69%), impending rupture (n = 3; 23%) and dilatation of the aorta with ongoing pain refractory to medical treatment (n = 1; 8%). Overall survival at the end of the follow-up period was 71%, with 77% in the surgical group and 63% in the conservative group (P = 0.91). Freedom from surgical intervention was 71%, with 82% in the surgical and 63% in the conservative group (P = 0.21), and freedom from a neurological event was 88%, with 89% versus 89% (P = 0.68) in the surgical and conservative groups, respectively. CONCLUSIONS: Aortic arch dissection is a rare pathological condition that is one of the most challenging decision-making entities. Patients manifesting an uneventful course not requiring a surgical intervention during a hospital stay were at a higher risk for aorta-related intervention during the follow-up period. The treatment modality had no impact on survival or on the incidence of a neurological event.

The management of lower limb arteriovenous grafts in the perioperative period following renal transplantation.

BACKGROUND: The presence of a lower limb arteriovenous graft (LL-AVG) is indicative of a group of complex hemodialysis patients who have precarious long-term vascular access. The aim of this study is to describe our experience of the clinical decisions and interactions between LL-AVG and renal transplantation. METHODS: The records of 23 patients who received a transplant in the presence of a LL-AVG between 2010 and 2018 were analyzed: firstly, to determine whether patients with a LL-AVG received extended criteria transplants, the implantation procedure, and the management of the LL-AVG in the post-operative period. RESULTS: Seventeen patients (74%) had "end-stage access" and were thus considered for all offer stratified by the kidney donor profile index (KDPI) and donor type (DBD or DCD). In eleven patients (48%), a kidney with a high risk of delayed graft function was transplanted. Same-sided renal transplantation occurred in only 35% of cases, and of these, only one LL-AVG was ligated immediately to improve transplant perfusion. CONCLUSION: A patient-based approach applied in decision-making on management of the LL-AVG post-transplantation should include (a) the likelihood of delayed graft function, (b) the need for post-operative hemodialysis, (c) the side of proposed transplant compared to the LL-AVG, and (d) local complications.

Therapeutic vascularization in regenerative medicine.

Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue-engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short-term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis.