UNASSIGNED: Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. Although previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on vein graft failure. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury.
UNASSIGNED: Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing and spatial transcriptomics analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-carotid vein bypass implantation in a canine model (n=4).
UNASSIGNED: Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P<0.05) involved in the activation of endothelial cells (ECs), fibroblasts, and vascular smooth muscle cells, namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and ECM (extracellular matrix) remodeling throughout the vein wall. Subsequent single-nuclei RNA-sequencing analysis supported these findings and further unveiled distinct EC and fibroblast subpopulations with significant upregulation (P<0.05) of markers related to endothelial injury response and cellular activation of ECs, fibroblasts, and vascular smooth muscle cells. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN, FBN1, and VEGFC, in addition to novel genes of interest, such as GLIS3 and EPHA3. These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9. By integrating the spatial transcriptomics and single-nuclei RNA-sequencing data sets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and fibroblasts were notably enriched in the intima and media of distended veins. Finally, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal-transitioning ECs, protomyofibroblasts, and vascular smooth muscle cells in upregulating signaling pathways associated with cellular proliferation (MDK [midkine], PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor]), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension.
UNASSIGNED: Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

BACKGROUND: Octogenarians are regarded as one of the frailest patient groups among the chronic limb-threatening ischaemia population with high perioperative morbidity and mortality rates. As a result, alternative vein bypass surgery in the absence of sufficient great saphenous vein is often not considered as a potential treatment option. The aim of this study was to compare the results of octogenarians undergoing alternative vein bypass surgery due to chronic limb-threatening ischaemia to younger patients.
METHODS: A single-centre retrospective analysis of patients undergoing bypass surgery for chronic limb-threatening ischaemia with alternative autologous vein grafts between 1997 and 2018 was performed. Patients aged over 80 years were compared with those under 80 years. Graft patency rates were assessed and a risk factor analysis for limb loss was performed.
RESULTS: In total, 592 patients underwent bypass surgery during the study interval. Twenty-one per cent (n = 126) of patients were 80 years or older. At 4 years, primary, primary-assisted and secondary patency as well as limb salvage rates were not significantly different between the two groups (46% versus 50%, 60% versus 66%, 69% versus 72%, 72% versus 77%, for octogenarians versus non-octogenarians respectively). Major amputations were performed in 27 (21%) octogenarians and 91 (20%) non-octogenarians (P = 0.190). No higher 30-day and long-term mortality rates nor morbidity rates were detected in the octogenarian group with a median follow-up time of 27 (interquartile range 12-56) months. Minor amputation, the reason for alternative vein grafts, as well as the profunda femoris artery as proximal origin of the bypass were risk factors for limb loss in the postoperative course.
CONCLUSIONS: Alternative vein bypass surgery in octogenarians with chronic limb-threatening ischaemia is safe and effective in terms of patency rates, limb salvage and survival compared with younger patients in the absence of sufficient great saphenous vein. Age alone should not be a deterrent from performing bypass surgery.

BACKGROUND: Portugal has one of the highest prevalence of patients on a regular dialysis program. This population has a higher incidence of peripheral arterial disease with higher rates of postoperative morbidity and mortality. Our goal was to compare outcomes between dialysis and non-dialysis patients with chronic limb threatening ischemia (CLTI) submitted to infrapopliteal bypass.
METHODS: A retrospective single-center study of infrapopliteal bypass for CLTI was performed between 2012 and 2019. Patients were divided in two groups based on dialysis status (group 1 incorporated patients on dialysis). Primary end point was 1-year freedom from CLTI. Secondary end points were limb-salvage, survival and primary (PP) and tertiary patency (TP) rates at 3 years of follow-up.
RESULTS: A total of 352 infrapopliteal bypasses were performed in 310 patients with CLTI. Fourteen percent of the revascularizations were performed on dialysis patients (48/352). Median age was 73 years (interquartile range - IQR 15) and 74% (259/352) were male. Median follow-up was 26 months (IQR 42). Overall, 92% (325/352) had tissue loss and 44% (154/352) had some degree of infection. The majority of revascularization procedures were performed with vein grafts (61%, 214/352). The 30-day mortality was 4% (11/310), with no difference between groups (p = 0.627). Kaplan-Meier analysis showed no difference between groups regarding freedom from CLTI (76% vs. 79%; HR 0.96, CI 0.65-1.44, p=0.857), limb-salvage (70% vs. 82%; HR 1.40, CI 0.71-2.78, p=0.327) and survival (62% vs. 64%; HR 1.08, CI 0.60-1.94, p=0.799). PP rates were 39% in group 1 and 64% in group 2 (HR 1.71, CI 1.05-2.79, p=0.030). TP rates were not different between groups (57% and 78%; HR 1.79, CI 0.92-3.47, p=0.082).
CONCLUSIONS: Infrapopliteal bypass for CLTI, on dialysis patients, resulted in lower PP rates. No differences were observed in freedom from CLTI, TP, limb salvage and survival.

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision-making for challenging presentations. This document will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta.

BACKGROUND: We investigated the long-term safety and efficacy of anatomical and extra-anatomical bypass for the treatment of unilateral iliac artery disease.
METHODS: A systematic search on PubMed, Scopus and Web of science for articles published by June 2023 was performed. We implemented a 2-stage individual participant data meta-analysis and pooled survival probabilities using the multivariate methodology of DerSimonian and Laird. The primary endpoint was primary patency at 5 and 10 years of follow-up.
RESULTS: Ten studies encompassing 1,907 patients were included. The 5- and 10-year pooled patency rates for anatomical bypass were 83.27% (95% confidence interval (CI): 69.99-99.07) and 77.30% (95% CI: 60.32-99.04), respectively, with a mean primary patency time representing the duration individuals remained event-free for 10.08 years (95% CI: 8.05-10.97). The 5- and 10-year pooled primary patency estimates for extra-anatomical bypass were 77.02% (95% CI: 66.79-88.80) and 68.54% (95% CI: 53.32-88.09), respectively, with a mean primary patency time of 9.25 years, (95% CI: 7.21-9.68). Upon 2-stage individual participant data meta-analysis, anatomical bypass displayed a decreased risk for loss of primary patency compared to extra-anatomical bypass, hazard ratio 0.51 (95% CI: 0.30-0.85). The 5- and 10-year secondary patency estimates for anatomical bypass were 96.83% (95% CI: 90.28-100) and 96.13% (95% CI: 88.72-100), respectively. The 5- and 10-year secondary patency estimates for extra-anatomical bypass were 91.39% (95% CI: 84.32-99.04) and 85.05% (95% CI: 74.43-97.18), respectively, with non-statistically significant difference between the 2 groups. The 5- and 10-year survival for patients undergoing anatomical bypass were 67.99% (95% CI: 53.84-85.85) and 41.09% (95% CI: 25.36-66.57), respectively. The 5- and 10-year survival for extra-anatomical bypass were 70.67% (95% CI: 56.76-87.98) and 34.85% (95% CI: 19.76-61.44), respectively. The mean survival time was 6.92 years (95% CI: 5.56-7.89) for the anatomical and 6.78 years (95% CI: 5.31-7.63) for the extra-anatomical groups. The pooled overall 30-day mortality was 2.32% (95% CI: 1.12-3.87) with metaregression analysis displaying a negative association between the year of publication and mortality (β =-0.0065, P < 0.01). Further analysis displayed a 30-day mortality of 1.29% (95% CI: 0.56-2.26) versus 4.02% (95% CI: 1.78-7.03), (P = 0.02) for studies published after and before the year 2000. Non-statistically significant differences were identified between the 2 groups concerning long-term and 30-day mortality outcomes.
CONCLUSIONS: While we have demonstrated favorable long-term primary and secondary patency outcomes for both surgical techniques, anatomical bypass exhibited a reduced risk of primary patency loss potentially reflecting its inherent capacity to circumvent the anticipated disease progression in the distal aorta and the contralateral donor artery. The reduction in perioperative mortality observed in our review, coupled with the anachronistic demographic characteristics and inclusion criteria presented in the existing literature, underscores the imperative necessity for contemporary research.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is characterized by rest pain and tissue loss, with an annual mortality rate of 20% and amputation rate of 40%, if not treated. Open bypass surgery is recommended in CLTI, depending on the availability of good quality venous material, outflow artery patency, and surgical expertise. The aim of the study is to analyze primary patency, limb salvage, and survival rate in patients undergoing popliteal-to-distal bypass.
METHODS: All consecutive patients who underwent popliteal-to-distal bypass surgery between January 2016 and December 2021 were enrolled in the study. Primary outcomes were primary patency, limb salvage, and overall survival. Secondary outcomes included amputation-free survival and secondary patency.
RESULTS: Forty-nine patients were included during the study. Technical success was achieved in 100% of cases. Target outflow artery was in 27% (n. 13) of cases the anterior tibial artery, in 27% (n. 13) the dorsalis pedis, in 2% (n. 1) the peroneal artery, in 30% (n. 15) the retromalleolar tibial artery, in 10% (n. 5) the medial plantar artery, and in 4% (n. 2) the tarsal artery. Two-year primary patency was 85% ± 5. Secondary patency rates were 86% ± 3 at 2 years. The overall survival was 81% ± 6 at 2 years, the amputation-free survival was 70% ± 9, and the limb salvage rate was 81% ± 6.
CONCLUSIONS: Popliteal-to-distal bypass requires high technical expertise to be performed. When a good autologous vein and adequate outflow artery are present, they can be feasible with good patency rates and overall survival.

Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall via activation of mechanosensitive signaling pathways and subsequent changes in gene expression and associated turnover of cells and extracellular matrix. In this review, we outline experimental and computational tools used to quantify metrics of biomechanical loading in vascular grafts and highlight those that show potential in predicting graft failure for diverse disease contexts. We include metrics derived from both fluid and solid mechanics that drive feedback loops between mechanobiological processes and changes in the biomechanical state that govern the natural history of vascular grafts. As illustrative examples, we consider application-specific coronary artery bypass grafts, peripheral vascular grafts, and tissue-engineered vascular grafts for congenital heart surgery as each of these involves unique circulatory environments, loading magnitudes, and graft materials.

Biotubes are autologous tubular tissues developed within a patient\'s body through in-body tissue architecture, and they demonstrate high potential for early clinical application as a vascular replacement. In this pilot study, we used large animals to perform implantation experiments in preparation for preclinical testing of Biotube. The biological response after Biotube implantation was histologically evaluated. The designed Biotubes (length: 50 cm, internal diameter: 4 mm, and wall thickness: 0.85 mm) were obtained by embedding molds on the backs of six goats for a predetermined period (1-5 months). The same goats underwent bypass surgery on the carotid arteries using Biotubes (average length: 12 cm). After implantation, echocardiography was used to periodically monitor patency and blood flow velocity. The maximum observation period was 6 months, and tissue analysis was conducted after graft removal, including the anastomosis. All molds generated Biotubes that exceeded the tensile strength of normal goat carotid arteries, and eight randomly selected Biotubes were implanted. Thrombotic occlusion occurred immediately postoperatively (1 tube) if anticoagulation was insufficient, and two tubes, with insufficient Biotube strength (<5 N), were ruptured within a week. Five tubes maintained patency for >2 months without aneurysm formation. The spots far from the anastomosis became stenosed within 3 months (3 tubes) when Biotubes had a wide intensity distribution, but the shape of the remaining two tubes remained unchanged for 6 months. The entire length of the bypass region was walled with an αSMA-positive cell layer, and an endothelial cell layer covered most of the lumen at 2 months. Complete endothelial laying of the luminal surface was obtained at 3 months after implantation, and a vascular wall structure similar to that of native blood vessels was formed, which was maintained even at 6 months. The stenosis was indicated to be caused by fibrin adhesion on the luminal surface, migration of repair macrophages, and granulation formation due to the overproliferation of αSMA-positive fibroblasts. We revealed the importance of Biotubes that are homogeneous, demonstrate a tensile strength > 5 N, and are implanted under appropriate antithrombotic conditions to achieve long-term patency of Biotube. Further, we clarified the Biotube regeneration process and the mechanism of stenosis. Finally, we obtained the necessary conditions for a confirmatory implant study planned shortly.

OBJECTIVE: This study aimed to evaluate treatment outcomes after bypass surgery or endovascular therapy (EVT) in average- and high-risk patients with chronic limb-threatening ischemia (CLTI).
METHODS: We retrospectively analyzed multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. A high-risk patient was defined as one with estimated 30-day mortality rate ≥5% or 2-year survival rate ≤50%, as determined by the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) calculator. The amputation-free survival (AFS), limb salvage (LS), wound healing, and 30-day mortality were compared separately for the average- and high-risk patients between the bypass and EVT with propensity score matching.
RESULTS: We analyzed 239 and 31 propensity score-matched pairs in the average- and high-risk patients with CLTI. In the average-risk patients, the 2-year AFS and LS rates were 78.1% and 94.4% in the bypass group and 63.0% and 87.7% in the EVT group (P < .001 and P = .007), respectively. The 1-year wound healing rates were 88.6% in the bypass group and 76.8% in the EVT group, respectively (P < .001). The 30-day mortality was 0.8% in the bypass surgery and 0.8% in the EVT group (P = .996). In the high-risk patients, there was no differences in the AFS, LS, and wound healing between the groups (P = .591, P = .148, and P = .074). The 30-day mortality was 3.2% in the bypass group and 3.2% in the EVT group (P = .991).
CONCLUSIONS: Bypass surgery is superior to EVT with respect to the AFS, LS, and wound healing in the average-risk patients. EVT is a feasible first-line treatment strategy for high-risk patients with CLTI undergoing revascularization, based on the lack of significant differences in the 2-year AFS rate, between the bypass surgery and EVT cohorts.

BACKGROUND: Alternative autologous veins can be used as a conduit when adequate great saphenous vein is unavailable. We analyzed the results of our infrainguinal bypasses after adopting upper extremity veins in our practice.
METHODS: This is a single-center observational study involving all patients whose infrainguinal bypass involved the use of upper extremity veins between April 2019, when we began using arm veins, and February 2023.
RESULTS: During the study period, 49 bypasses were done in 48 patients; mean age 68.1 ± 9.8; men 32 (66.7%); body mass index 28.0 ± 4.8; indications for surgery: chronic limb threatening ischemia 41 (83.7%); acute limb ischemia 3 (6.1%); complications of previous prosthetic 3 (6.1%), or autologous 2 (4.1%) bypass grafts. Vein splicing was used in 43 (87.8%) bypasses with 3-segment grafts being the most common (26; 53.1%). There were 24 (49.0%) femorotibial, 11 (22.4%) femoropopliteal, 9 (18.4%) femoropedal, and 5 (10.2%) extension jump bypass procedures. Eighteen (36.7%) operations were redo surgeries. Twenty-one (42.9%) bypasses were formed using only arm veins. The median follow-up was 12.9 months (4.5-24.2). Two bypasses occluded during the first 30 postoperative days (2/49; 4.1%). Overall 30-day, 1-year, and 2-year primary patency rates were 93.7% ± 3.5%, 84.8% ± 5.9%, and 80.6% ± 6.9%, and secondary patency (SP) rates were 95.8% ± 2.9%, 89.2% ± 5.3%, and 89.2% ± 5.3%. One-segment grafts had better patencies than 2-, 3-, and 4-segment grafts (1-year SP 100% ± 0% vs 87.6% ± 6.0%). Two-year amputation-free survival was 86.8% ± 6.5%; 2-year overall survival was 88.2% ± 6.6%.
CONCLUSIONS: Integration of arm vein grafts in infrainguinal bypass practice can be done safely with low incidences of perioperative graft failure. One-segment grafts had better patencies than spliced vein grafts. The achieved early patency and amputation-free survival rates strongly encourage their use. In the absence of a single-segment great saphenous vein, upper extremity vein grafts should be the preferred conduit choice.