Peak Aortic Valve Jet Velocity is an Independent Predictor of Mortality of Dialysis Patients Undergoing Open Surgery for Chronic Limb Threatening Ischemia.

BACKGROUND: To investigate the impact of peak aortic jet velocity (Vmax) on the prognosis of patients undergoing open surgery for chronic limb threatening ischemia (CLTI). METHODS: Between April 2015 and March 2022, 352 patients underwent infrainguinal open surgery for CLTI. Patients who met the following exclusion criteria were excluded: subsequent infrainguinal surgeries in the registered period, no record of Vmax, history of aortic valve intervention, and Vmax ≥3.0 m/s (moderate or severe aortic valve stenosis). The remaining patients were dichotomized into 2 groups based on their Vmax values. The Youden index calculated from the receiver operating characteristic curve (ROC) was set as the cutoff value. The 2-year overall survival (OS), calculated using the Kaplan-Meier's method, was compared between the 2 groups. A Cox proportional hazards regression analysis was performed using perioperative factors including Vmax to identify independent predictors separately for dialysis and nondialysis patients and the quantitative relationship between Vmax and OS. RESULTS: One hundred and ninety-one patients, including 100 dialysis and 91 nondialysis patients, were included in the analysis. The Youden index was 1.7 m/s. The 2-year OS rates of the group with Vmax >1.7 m/s and with Vmax ≤1.7 m/s were 49% and 76% (P = 0.007), respectively, in the dialysis cohort, while they were 71% and 78% (P = 0.680) in the nondialysis cohort, respectively. Multivariate analysis identified Vmax and ejection fraction as independent predictors in the dialysis cohort and the Barthel Index at admission in the nondialysis cohort. There was a stepwise increase in the risk of death in patients with Vmax of ≥1.5 m/s and a significantly higher risk of death in dialysis patients with Vmax >2.5 m/s. CONCLUSIONS: Vmax was a significant independent predictor of all-cause death within 2 years after open surgery for CLTI in dialysis patients but not in patients managed without dialysis.

Experience of Balloon Aortic Valvuloplasty for Severe Aortic Stenosis in Patients Scheduled for Open Surgery for Chronic Limb-Threatening Ischemia.

Objectives: To estimate the effectiveness of balloon aortic valvuloplasty (BAV) for severe aortic stenosis (SAS) in patients scheduled for open surgery for chronic limb-threatening ischemia. Materials and Methods: Clinical data of patients from 2012 to 2018 were retrieved and summarized. The early outcomes and survival after BAV and open bypass were retrospectively investigated. Results: BAV was performed on seven dialysis patients. One patient died of mesenteric infarction 3 days after BAV; however, six patients were able to undergo open bypass at an average of 10 days (7-19 days) after BAV. One patient died of hemorrhagic shock before the wound healed; five patients underwent limb salvage. Four of these five patients could not undergo surgical aortic open valve replacement owing to advanced age or poor cardiac function and died within 2 years. Only one patient who underwent radical surgery after a bypass survived more than 4 years. Conclusion: BAV enabled open surgery and limb salvage in patients with SAS. Although BAV alone cannot ensure long-term survival, the procedure will continue to be important as a bridge technique to radical surgery, such as transcatheter aortic valve implantation and aortic valve repair, which are often avoided owing to infection.

Left Renal Vein Division during Open Surgical Repair for Abdominal Aortic Aneurysm May Cause Long-Term Kidney Remodeling.

BACKGROUND: Left renal vein division (LRVD) is a maneuver performed during open surgical repair for abdominal aortic aneurysms. Even so, the long-term effects of LRVD on renal remodeling are unknown. Therefore, we hypothesized that interrupting the venous return of the left renal vein might cause renal congestion and fibrotic remodeling of the left kidney. METHODS: We used a murine left renal vein ligation model with 8-week-old to 12-week-old wild-type male mice. Bilateral kidneys and blood samples were harvested postoperatively on days 1, 3, 7, and 14. We assessed the renal function and the pathohistological changes in the left kidneys. In addition, we retrospectively analyzed 174 patients with open surgical repairs between 2006 and 2015 to assess the influence of LRVD on clinical data. RESULTS: Temporary renal decline with left kidney swelling occurred in a murine left renal vein ligation model. In the pathohistological assessment of the left kidney, macrophage accumulation, necrotic atrophy, and renal fibrosis were observed. In addition, Myofibroblast-like macrophage, which is involved in renal fibrosis, was observed in the left kidney. We also noted that LRVD was associated with temporary renal decline and left kidney swelling. LRVD did not, however, impair renal function in long-term observation. Additionally, the relative cortical thickness of the left kidney in the LRVD group was significantly lower than that of the right kidney. These findings indicated that LRVD was associated with left kidney remodeling. CONCLUSIONS: Venous return interruption of the left renal vein is associated with left kidney remodeling. Furthermore, interruption in the venous return of the left renal vein does not correlate with chronic renal failure. Therefore, we suggest careful follow-up of renal function after LRVD.

Perioperative therapeutic antibiotics are beneficial to prevent exacerbation of limb-associated infection after bypass surgery in patients with critical limb-threatening ischemia and foot infection score of ≥1.

OBJECTIVE: Postoperative limb infection is associated with a poor prognosis and a low amputation-free survival rate after surgical revascularization in patients with critical limb-threatening ischemia. The Global Vascular Guidelines 2019 recommend antibiotic therapy for patients with deep space foot infection or wet gangrene; however, no study is cited as evidence for this recommendation. The present study was performed to offer new evidence supporting the use of perioperative therapeutic antibiotics in patients with critical limb-threatening ischemia (CLTI) undergoing surgical revascularization. METHODS: This single-center retrospective study was performed in Kyushu University Hospital and involved patients with CLTI who underwent surgical revascularization from 2003 to 2021. Ampicillin/sulbactam and cefazolin were defined as preventive antibiotics, and other types were defined as therapeutic antibiotics. Postoperative limb-associated infection was defined as an increased foot infection (fI) score in the Wound, Ischemia, and foot Infection (WIfI) classification system after surgical revascularization. The association between perioperative antibiotic therapy and postoperative limb-associated infection was assessed. RESULTS: Among 286 limbs of 263 patients with CLTI, 27 (9%) limbs developed postoperative limb-associated infection after surgical revascularization. The fI scores were significantly higher in the patients with than without postoperative limb-associated infection (1.0 ± 0.2 vs 0.4 ± 0.1, respectively; p = 0.0033), indicating that an fI score of ≥1 was a risk factor for postoperative limb-associated infection. Perioperative therapeutic antibiotics significantly reduced the incidence of postoperative limb-associated infection compared with preventive antibiotics (0.0% vs. 44.8%, respectively; p = 0.0028) in the patients with CLTI who had an fI score of ≥1 after bypass surgery, although perioperative therapeutic antibiotics were not effective for patients with an fI score of 0. CONCLUSION: Perioperative therapeutic antibiotics for patients with an fI score of ≥1 are beneficial for reducing the incidence of postoperative limb-associated infection after surgical revascularization.

Interleukin-38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2-p38 pathway-dependent manner.

Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin-38 (IL-38) is a member of the IL-1 family, which binds to IL-36 receptor (IL1RL2) and has an anti-inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL-38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II-induced AAA model with or without IL-38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor-α and treated with or without IL-38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL-38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2+ macrophage accumulation along with matrix metalloproteinase (MMP)-2 and -9 expression was observed in mouse AAA. IL-38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP-2 and -9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP-2, and MMP-9 production and spindle-shaped changes were significantly suppressed by IL-38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL-38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL-38 depend on the p38 pathway. IL-38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL-38 may be a novel therapy for AAA patients.

Evaluation of three nutritional indices as predictors of 2-year mortality and major amputation in patients with chronic limb-threatening ischemia.

OBJECTIVE: The present study aimed to examine which nutritional index, such as the controlling nutritional status (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), is better for predicting prognosis in patients with chronic limb-threatening ischemia (CLTI) following revascularization. METHOD: We retrospectively analyzed data of patients who underwent revascularization for CLTI between 2008 and 2020. The endpoints were 2-year overall survival and limb salvage. The optimal cutoff values of 2-year overall survival and major amputation were determined by receiver operating characteristic curve analyses. RESULT: A total of 238 patients with CLTI and 289 limbs were analyzed. The 2-year overall survival rates were 48.9%, 54.6%, and 53.5% in patients with CONUT score ≥4, PNI score <42.6, and GNRI <98.4 compared with 80.0%, 80.0%, and 78.4% in patients with CONUT score <4, PNI score ≥42.6, and GNRI ≥98.4 (p < 0.01). Age, non-ambulatory status, hemodialysis, and nutritional indices were independent risk factors for 2-year mortality in the multivariate analyses. The 2-year limb salvage rates were 70.1%, 82.2%, and 81.9% in patients with CONUT score ≥7, PNI score <41.9, and GNRI <95.3 compared with 92.8%, 98.3%, and 94.2% in patients with CONUT score <7, PNI score ≥41.9, and GNRI ≥95.3 (p < 0.01). Wound, ischemia, and foot infection stage and each nutritional index (CONUT and PNI) were independent risk factors for major amputation in multivariate analyses. The overall survival and limb salvage rates of patients with malnutrition diagnosed by CONUT score were poor compared with those of normal nutrition or malnutrition diagnosed by PNI and/or GNRI scores. CONCLUSION: The CONUT, PNI, and GNRI scores can predict the 2-year overall survival in patients with CLTI after revascularization. The CONUT and PNI scores were associated with major amputation.

Global Limb Anatomic Staging System Inframalleolar Modifier Predicts Limb Salvage and Wound Healing in Patients with Chronic Limb Threatening Ischaemia Undergoing Endovascular Infrainguinal Revascularisation.

OBJECTIVE: This study aimed to analyse the influence of the Global Anatomic Staging System (GLASS) and inframalleolar (IM) disease on the treatment outcomes of patients with chronic limb threatening ischaemia (CLTI) who undergo endovascular treatment (EVT) METHODS: Data of patients who underwent infrainguinal endovascular therapy (EVT) for CLTI between 2015 and 2019 at two centres were analysed retrospectively. The endpoints were major amputation, major adverse limb events (MALE), and wound healing. RESULTS: Overall, 276 patients and 340 limbs were analysed. The number of revascularisations for an infrapopliteal lesion was 48 (70.6%), 63 (63.0%), and 142 (82.6%) in the GLASS I, GLASS II, and GLASS III stages, respectively (p < .001). There was no statistically significant difference in limb salvage among the GLASS stages (p = .78). The limb salvage rates at one year were 94.6%, 88.0%, and 70.0% in the IM P0 P1, and P2 groups, respectively (p < .001). Multivariable analysis showed that Wound, Ischemia, and foot Infection (WIfI) stage, and IM grade were risk factors for major amputation. The freedom from MALE rates at two years were 60.5%, 45.3%, and 41.1% in the GLASS I, II, and III stages, respectively (p = .003) and 64.1%, 43.5%, and 18.4% in the IM P0, P1, and P2 groups, respectively (p < .001). Multivariable analysis demonstrated that WIfI stage, GLASS stage, IM grade, and infrapopliteal revascularisation were risk factors for MALE. There was no significant difference in wound healing among GLASS I - III (p = .75). The wound healing rates at 365 days were 78.6%, 68.6%, and 42.0% in the IM P0, P1, and P2 groups, respectively (p = .065). Multivariable analysis showed that WIfI stage and IM P2 were risk factors for incomplete wound healing. CONCLUSION: GLASS IM was associated with major amputation, MALE, and wound healing, while GLASS stage was associated with only MALE.

A systematic review of management of ureteroarterial fistula.

OBJECTIVE: Ureteroarterial fistula (UAF) is lethal condition. However, no consensus has been reached regarding the diagnosis and treatment of UAF owing to its rarity. The aim of our report was to present an actual case of UAF and systematically review the symptoms, risk factors, diagnosis, and treatment of this condition. METHODS: The case study was of a 52-year-old woman who had experienced a massive hemorrhage during urinary stent replacement. For the systematic review of studies of UAF, those written in English and reported from 1939 to 2020 were searched for on PubMed using the keywords "uretero-arterial fistula," "arterio-ureteral fistula," and "hematuria." RESULTS: We included 121 studies with 235 patients (mean age, 66.0 years; 139 women [59.1%]) in our review. UAF had occurred most frequently in the common iliac artery (n = 112; 47.7%). Almost all patients (n = 232; 98.7%) had complained of hematuria. The risk factors for UAF were pelvic surgery (n = 205; 87.2%), the long-term use of urinary stents (n = 170; 72.3%), oncologic radiotherapy (n = 107; 45.5%), and malignancy (n = 159; 67.7%). Although computed tomography can detect various useful findings such as extravasation, pseudoaneurysm, hydronephrosis, and opacification of ureters, it was diagnostically useful for only one third of the cases. Angiography was useful for the diagnoses of UAF for 124 (66.3%) of the 187 patients (79.6%) who had undergone angiography. With regard to treatment, endovascular approaches have been widely used in recent years because their invasiveness is lesser than that of open surgical repair. In the era of endovascular therapy, the indications for open surgical repair include ureteral-intestinal fistula, abscess formation, and graft infection after endovascular therapy. CONCLUSIONS: Computed tomography can be recommended as the first examination for patients with risk factors for UAF because of its usefulness. Subsequently, angiography should be considered because UAF can be treated using an endovascular approach after diagnostic angiography. The diagnosis and treatment of UAF can often be difficult; therefore, the important first step of diagnosis is suspecting the occurrence of UAF and using a multidisciplinary approach.

Internal Iliac Artery Aneurysm Ruptures with No Visualized Endoleak 2 Years after Endovascular Repair.

We report a case of an 83-year-old man with a ruptured internal iliac artery (IIA) aneurysm after endovascular repair, which was treated via the ligation of IIA and tight suture of the aneurysm sac. Although there were no findings of obvious endoleak after endovascular treatment, the IIA aneurysm increased in size and eventually ruptured. We presumed that pressure to IIA aneurysm via the embolized IIA led to rupture. Aneurysm sac expansion may lead to a rupture despite no endoleak being detected; therefore, close follow-up or re-intervention must be considered. Tight embolization of IIA may prevent endotension in the same case.

Effect of abdominal aortic aneurysm sac shrinkage after endovascular repair on long-term outcomes between favorable and hostile neck anatomy.

OBJECTIVE: The aim of the present study was to analyze the influence of abdominal aortic aneurysm sac shrinkage on the long-term outcomes after endovascular aneurysm repair (EVAR) between patients with favorable and hostile neck anatomy. METHODS: In the present study, we retrospectively analyzed data from 268 patients with fusiform aneurysm and sac behavior who had been evaluated for ≥1 year after EVAR. Hostile neck anatomy was defined as a proximal aneurysmal neck length of <10 mm or proximal neck angle of ≥60°. The primary end point was sac shrinkage, and the secondary end points included reintervention and a composite of rupture, type Ia endoleak, and late open conversion. RESULTS: No differences were found in sac shrinkage between the patients with favorable and hostile neck anatomy (P = .47). Multivariate analysis revealed that an occluded inferior mesenteric artery (P = .04), the presence of posterior thrombus (P < .01), and no antiplatelet therapy (P = .01) were positive factors for sac shrinkage. The reintervention-free survival rate was better for patients with sac shrinkage compared with those without sac shrinkage regardless of the proximal neck anatomy (P < .01). The event-free survival rate of the composite end point at 5 and 10 years was 97.5% and 83.5% for patients with favorable neck anatomy and 86.8% and 81.0% for those with hostile neck anatomy, respectively (P = .02). In the subgroup with sac shrinkage, the event-free survival rates at 5 and 10 years were 98.7% and 98.7% for those with favorable neck anatomy and 92.7% and 82.4% for those with hostile neck anatomy, respectively (P = .02). In contrast, the event-free survival for patients without sac shrinkage did not differ between those with favorable and hostile neck anatomy (P = .08). Multivariate analysis showed that a hostile neck anatomy (hazard ratio, 3.32; 95% confidence interval, 1.26-8.80; P = .02) and no sac shrinkage (hazard ratio, 3.88; 95% confidence interval, 1.25-12.0; P = .02) were significant risk factors for the composite end point of rupture, type Ia endoleak, and late open conversion. CONCLUSIONS: Proximal neck anatomy did not affect sac shrinkage after EVAR. Sac shrinkage has been a good surrogate marker of better long-term outcomes after EVAR for patients with favorable neck anatomy. In contrast, critical events such as rupture and type Ia endoleak can occur even after sac shrinkage has been achieved in patients with hostile neck anatomy.

Bypass Surgery Provides Better Outcomes Compared with Endovascular Therapy in the Composite Endpoint Comprising Relief from Rest Pain, Wound Healing, Limb Salvage, and Survival after Infra-inguinal Revascularisation in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: The present study aimed to determine the factors related to relief from rest pain, wound healing, major adverse limb events (MALEs), and prognosis after infrainguinal revascularisation in patients with chronic limb threatening ischaemia (CLTI). METHODS: The data of patients who underwent infrainguinal revascularisation for CLTI between 2010 and 2020 was analysed retrospectively. The endpoint was the composite of relief from rest pain, wound healing, MALE, or death. RESULTS: A total of 234 limbs in 187 patients with CLTI were analysed. Of the 234 limbs, 149 (63.7%) underwent bypass surgery and 85 (36.3%) underwent endovascular therapy (EVT). The event free survival rates with respect to the composite endpoint at two years were 30.4% in the EVT and 48.5% in the bypass groups, respectively (p = .005). The event free survival rates at two years were 56.7% in bypass surgery and 29.5% in EVT in the indeterminate subgroup (p = .051). Multivariable analysis revealed that age (hazard ratio [HR] 1.03; 95% confidence interval [CI] 1.01 - 1.05; p < .001), coronary artery disease (CAD) (HR 1.45; 95% CI 1.01 - 2.07; p = .042), haemodialysis (HR 1.74; 95% CI 1.22 - 2.48; p = .002), Wound, Ischaemia and foot Infection stage (HR 1.34; 95% CI 1.07 - 1.68; p = .012), Global Limb Anatomical Staging System stage (HR 1.31; 95% CI 1.01 - 1.72; p = .043), EVT (HR 1.90; 95% CI 1.31 - 2.74; p < .001), Geriatric Nutritional Risk Index (HR 0.98; 95% CI 0.97 - 0.99; p = .021), and non-ambulatory status (HR 1.89; 95% CI 1.31 - 2.74; p < .001) were risk factors for the composite endpoint. CONCLUSION: Bypass surgery is superior to EVT with respect to the composite endpoint including relief from rest pain, wound healing, MALE, or death. Bypass surgery may be considered as the treatment of choice, instead of EVT, in patients in the indeterminate group according to the Global Vascular Guidelines preferred revascularisation method.

Effects of Antithrombotic Therapy on Abdominal Aortic Aneurysm Sac Size after Endovascular Repair in Patients with Favorable Neck Anatomy.

PURPOSE: To evaluate the influence of antiplatelet or anticoagulant therapy on sac behavior after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: This study retrospectively analyzed data from patients with favorable neck anatomy who underwent EVAR between 2007 and 2019. Patients with ruptured AAA and ≤1 year of sac behavior evaluation were excluded. Sac shrinkage after 1 year, persistent type II endoleak, and late sac expansion were examined. RESULTS: In total, 182 patients with favorable neck anatomy were included in this study. A multivariable analysis identified an occluded inferior mesenteric artery (IMA; P = .049), the presence of a posterior thrombus (P = .009), and no antiplatelet therapy (P = .012) as factors positively associated with sac shrinkage at 1 year. Persistent type II endoleak was detected in 56 (30.8%) patients, with patent IMA (P = .006), the lack of a posterior thrombus (P = .004), the number of patent lumbar arteries (P = .004), and antiplatelet therapy (P = .039) being identified as significant risk factors. The multivariable analysis identified a larger initial AAA diameter (P < .001), the lack of a posterior thrombus (P = .038), and antiplatelet and anticoagulant therapies (P = .038 and P = .003, respectively) as risk factors for late sac expansion. CONCLUSIONS: After EVAR in patients with favorable neck anatomy, antiplatelet therapy is associated with the lack of sac regression at 1 year, whereas antiplatelet and anticoagulant therapies are risk factors for late sac expansion.

Iliac Artery Aneurysms Expand in Quadratically Proportion to the Diameter.

BACKGROUND: Iliac artery aneurysms (IAAs) are life-threatening once ruptured. Although some studies have revealed the pathology of IAAs, clinical information on IAAs is still limited. Moreover, previous studies were conducted in Western countries; thus, we aimed to identify the natural history of iliac artery aneurysms in a Japanese cohort. The purpose of this study was to investigate the IAA expansion rate in a Japanese cohort to consider the management of small IAAs and to identify indications for surgical intervention. METHODS: Patients with iliac artery aneurysms were retrospectively reviewed. The primary outcome was the expansion rate of IAAs. We also investigated the correlation between expansion rate and patients' characteristics. Natural histories, including surgical interventions and rupture, were also assessed. RESULTS: The mean expansion rate in our study was 1.59 ± 1.16 mm/year. There was a positive correlation between expansion rate and aneurysm diameter, which was estimated by y = 0.0052 × (X - 23.270)2 + 0.0632 × X - 0.0517, where y is the expansion rate, and X is aneurysm diameter. The freedom from surgical intervention rate of IAAs was 85.5% at 1 year, 54.0% at 3 years, and 41.5% at 5 years. No factors, except initial aneurysm diameter, were revealed as independent predictors of surgical intervention. We experienced one ruptured IAA, which showed unexpected rapid growth from 30.1 mm to 56.3 mm over 15 months during conservative management. This case demonstrated that IAAs ≥30 mm should be carefully followed up and considered for surgical intervention. CONCLUSIONS: We conclude that larger aneurysms have greater expansion rates. Because IAAs ≥30 mm carry a risk of rapid expansion resulting in rupture, careful follow-up, and surgical intervention should be performed if iliac artery aneurysms are ≥30 mm in diameter.

Validation of the GLASS Staging Systems in Patients With Chronic Limb-Threatening Ischemia Undergoing De Novo Infrainguinal Revascularization.

OBJECTIVES: The Global Limb Anatomic Staging System (GLASS) was proposed for evaluating the anatomic complexity of arterial disease in patients with chronic limb-threatening ischemia (CLTI). We aimed to examine the relationship between GLASS stage and treatment outcomes after infrainguinal revascularization in patients with CLTI. METHODS: We retrospectively analyzed data of patients undergoing infrainguinal revascularization for CLTI between 2010 and 2018 to examine whether GLASS stage affects the limb salvage, wound healing, and overall survival (OS). RESULTS: Throughout the study period, 153 CLTI patients and 190 limbs with Fontaine classification III and IV were analyzed for major amputation and OS, and 125 patients and 157 limbs of Fontaine classification IV were analyzed for wound healing. The number of patients with WIfI stage 1, 2, 3, and 4 was 14 (7.4%), 44 (23.2%), 65 (34.2%), and 67 (53.3%), respectively. The number of patients with GLASS stage I, II, and III was 23 (12.1%), 48 (25.3%), and 119 (62.6%), respectively. Among the 190 limbs, the number subject to bypass surgery, endovascular therapy, and hybrid therapy was 132 (69.5%), 39 (20.5%), and 19 (10.0%), respectively. A multivariate analysis showed that only WIfI stage and inframalleolar (IM) disease were risk factors for major amputation and impaired wound healing. There was no relationship between GLASS stage and limb salvage or wound healing. A multivariate analysis revealed that age, geriatric nutritional risk index and GLASS stage were risk factors for 2-year OS (P < 0.01). Patients with all risk factors had a poor prognosis (35.3% at 2 years). CONCLUSION: WIfI stage and IM disease predicted limb salvage and wound healing after infrainguinal revascularization in patients with CLTI. Although GLASS stage did not affect limb salvage or wound healing, it was a prognostic factor for poor OS. The GLASS staging could be useful for deciding between bypass surgery and endovascular therapy in prediction of prognosis.

Analysis of prognostic factors for postoperative complications and reinterventions after open surgical repair and endovascular aneurysm repair in patients with abdominal aortic aneurysm.

OBJECTIVE: A definitive treatment for patients with abdominal aortic aneurysm considering age and comorbidities has not been identified. In the present study, we retrospectively validated treatment outcomes in Japanese patients and proposed the treatment strategy of open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: We retrospectively analyzed data for patients undergoing EVAR or OSR between 2006 and 2017. Patients with ruptured abdominal aortic aneurysm were excluded. We examined post-operative complications, operative mortality, re-intervention and prognosis. RESULTS: Throughout the study period, 405 patients underwent EVAR and 176 patients underwent OSR. The percentage of patients with post-operative complications was 35.8% in the OSR group, compared with 13.1% in the EVAR group (P < 0.01). The operative mortality rate was 0.49% in the EVAR group and 0.57% in the OSR group (P = 1.00). With a multivariate analysis, age, hemodialysis, modified Frailty Index (mFI), and OSR were risk factors for post-operative complications. The 5-year re-intervention free survival rate was 63.0 % with hostile neck EVAR compared with 83.1 % with favorable neck EVAR and 86.1 % with OSR group (P < 0.01). With a multivariate analysis, hemodialysis, mFI, and hostile neck EVAR were risk factors for re-intervention. The 5-year overall survival rate was 51.9 % with hostile neck EVAR compared with 73.2 % with favorable neck EVAR and 79.0 % with OSR group (P < 0.01). With a multivariate analysis, age, mFI, and hostile neck EVAR were poor prognostic factors. CONCLUSION: Age, mFI, hemodialysis and hostile neck anatomy are useful predictors of post-operative complications, re-intervention and overall survival, and could be useful for informing treatment selection between OSR and EVAR.

Platelet Count Recovery after Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm.

Objective: To find a new predictor of endoleak (EL) and aneurysm sac expansion after endovascular aneurysm repair (EVAR), we evaluated the platelet count recovery (PCR) process after EVAR. Materials and Methods: Two hundred five patients treated with elective EVAR from 2007 to 2015 were retrospectively analyzed. We compared the platelet count ratio until postoperative day (POD) 7 to the presurgical baseline between patients with and without persistent EL (≥ 6 months). Subsequently, we calculated the optimal platelet count ratio for distinguishing persistent EL using receiver-operating characteristics analysis. A platelet count ratio on POD7 ≥118% was defined as the PCR. We evaluated the PCR's influence on the cumulative aneurysm sac expansion rate. Results: The average platelet count ratio on POD7 rose above baseline (112%), and the ratio was attenuated by persistent EL (103%). Of 205 patients, 126 (61%) were assigned to the disturbed PCR group (PCR(-) group). Cumulative aneurysm sac expansion rate was higher in the PCR(-) group than the PCR(+) group (34.4% vs. 12.8% in 5 years, p=0.01). Conclusion: Disturbed PCR after EVAR may be associated with ELs and eventual aneurysm sac expansion.

Influence of Internal Iliac Artery Embolization during Endovascular Aortic Repair Regarding Postoperative Sarcopenia and Midterm Survival.

BACKGROUND: Postoperative sarcopenia is a risk factor for postoperative mortality. Internal iliac artery embolization (IIAE) during endovascular aortic repair (EVAR) has ischemic effects on pelvic skeletal muscles because IIAE causes buttock claudication. The long-term effects of IIAE on pelvic skeletal muscle, however, have not been well investigated. We hypothesized that IIAE after EVAR induces a decrease in skeletal muscle, which leads to postoperative sarcopenia. MATERIALS AND METHODS: Patients with abdominal aortic aneurysms who underwent EVAR from 2009 to 2014 were retrospectively reviewed. Skeletal muscle areas (SMAs) at the third lumbar level and the mid-femoral level were measured on transverse computed tomographic images. Postoperative sarcopenia was defined as a >10% decrease in the L3 SMA as established in a previous study. We assessed the association between postoperative sarcopenia and IIAE. RESULTS: Altogether, 102 eligible patients who underwent elective EVAR comprised the study group. The L3 SMA at the 3-year follow-up evaluation was significantly smaller in patients with than without IIAE (P < 0.05). The SMAs of the psoas, lumbar, and thigh muscles were significantly smaller on the IIAE than non-IIAE side (P < 0.05). IIAE was thus revealed as an independent risk factor for postoperative sarcopenia (hazard ratio, 4.69; P = 0.008). In addition, patients who developed postoperative sarcopenia had a lower overall survival rate than those without postoperative sarcopenia (P < 0.001). CONCLUSIONS: IIAE during EVAR is a risk factor for postoperative sarcopenia, which is in turn associated with mortality. Hence, we should preserve the internal iliac artery whenever possible. Alternatively, if IIAE is deemed necessary, we should postoperatively institute protocols to prevent sarcopenia from developing.

Thigh sarcopenia and hypoalbuminemia predict impaired overall survival after infrainguinal revascularization in patients with critical limb ischemia.

OBJECTIVE: This study was performed to determine whether thigh sarcopenia can serve as a clinically relevant predictor of postoperative complications and overall survival after revascularization in patients with critical limb ischemia. METHODS: Patients who underwent preoperative computed tomography followed by infrainguinal revascularization from 2006 to 2015 were retrospectively analyzed. An axial computed tomography image was obtained at the midpoint of a line extending from the superior border of the patella to the greater trochanter of the femur. The thigh muscle area and bone area were measured. Thigh sarcopenia was defined as thigh muscle area/thigh bone area of <9. RESULTS: We included 117 patients with critical limb ischemia who underwent infrainguinal revascularization. The overall survival rates at two years were 86.5% and 55.1% in the thigh sarcopenia (-) and (+) groups, respectively (p < 0.01). The multivariate analysis showed that thigh sarcopenia (hazard ratio, 2.64; 95% confidence interval, 1.11-6.70; p = 0.03), cerebrovascular disease (hazard ratio, 3.18; 95% confidence interval, 1.31-7.36; p = 0.01), and serum albumin level (1 g/dL per increments) (hazard ratio, 0.41; 95% confidence interval, 0.21-0.81; p = 0.01) were the risk factors for overall survival two years after revascularization. CONCLUSION: Thigh sarcopenia is a risk factor for two-year overall survival in patients with critical limb ischemia after infrainguinal revascularization.

Therapeutic Arteriogenesis/Angiogenesis for Peripheral Arterial Disease by Nanoparticle-Mediated Delivery of Pitavastatin into Vascular Endothelial Cells.

Two decades have passed since therapeutic angiogenesis was proposed to promote reparative collateral growth as an alternative therapy for ischemic diseases in patients for whom neither surgical revascularization nor endovascular therapy was suitable. When therapeutic angiogenesis first began, local administration was conducted using recombinant growth factor proteins or gene-encoding growth factors for endothelial cells. Since then, autologous stem cells and endothelial progenitor cell transplantation therapy have been developed. Although many clinical trials have been performed on patients, most therapies have not yet become standard treatments. We have developed a nanoparticle (NP)-mediated, drug-targeting delivery system using bioabsorbable poly-lactic/glycolic acid (PLGA) NPs. In several animal models, pitavastatin-incorporated (Pitava)-NPs showed significant therapeutic effects on critical limb ischemia. Because PLGA NPs are delivered selectively to vascular endothelial cells after intramuscular administration, it is suggested that therapeutic angiogenesis/arteriogenesis plays an important role in the mechanism by which Pitava-NPs exert beneficial therapeutic effects. To translate this to clinical medicine, we have performed studies and produced Pitava-NPs in compliance with good laboratory practice/good manufacturing practice regulations, and completed a phase I/II clinical trial, reporting the safety and efficacy of Pitava-NP intramuscular injection for patients with critical limb ischemia. This review will focus on therapeutic angiogenesis/arteriogenesis for peripheral arterial disease induced by Pitava-NPs.

Platelets reflect the fate of type II endoleak after endovascular aneurysm repair.

OBJECTIVE: The management of type II endoleak (T2E) remains controversial because of the heterogeneous outcome. For blood-based screening to detect malignant T2E, we focused on platelets after endovascular aneurysm repair (EVAR) and compared them with the prognosis of T2Es. METHODS: From 2007 to 2015, there were 249 patients treated with EVAR for abdominal aortic aneurysm who were evaluated retrospectively. The mean follow-up period was 3.5 ± 0.2 years. T2Es that had aneurysm sac enlargement or converted to type I or type III endoleak were defined as malignant; the other T2Es were considered benign. Cases without any complications, including T2E, were defined as completed. We compared the platelet count on postoperative days (PODs) 1 to 7 with preoperative baseline values among the three groups. Sequentially, we calculated the cutoff of the platelet ratio on POD 7 to the baseline value in relation to malignant T2E using receiver operating characteristic analysis, and the cutoff ratio was 113% (sensitivity, 79%; specificity, 58%). We then reclassified T2E patients into T2E-high platelet (T2E-HP; ≥113%) or T2E-low platelet (T2E-LP; <113%) groups. The influence of platelets on T2E was evaluated with reintervention rate and cumulative aneurysm sac enlargement rate using the Kaplan-Meier method. RESULTS: T2Es were found in 70 patients (28%), and 179 patients were assigned to the completed group. Malignant and benign T2Es were found in 33 and 37 patients, respectively. No difference was found in the preoperative baseline values. On POD 7, the platelet count in the malignant T2E group was significantly lower than that in the completed and benign T2E groups (168 × 103/µL vs 207 × 103/µL and 201 × 103/µL; P = .0124). Then, 27 and 43 patients were assigned to the T2E-HP and T2E-LP groups, respectively. The reintervention-free survival rate in the T2E-LP group was lower than that in the completed group (at 3 years, 66.4% ± 8.0% vs 71.9% ± 4.0%; P = .0031). Among T2E patients, the cumulative aneurysm sac enlargement rates in the T2E-LP group were significantly higher than those in the T2E-HP group (at 3 years, 34.6% ± 8.2% vs 20.6% ± 8.2%; P = .0105). Univariate Cox proportional hazards analysis for the cumulative aneurysm sac enlargement rates among T2E patients showed that sex, dual antiplatelet therapy, and lower platelet ratio (<113%) were significant predictors; multivariate analysis showed that T2E-LP was the only significant predictor (hazard ratio, 2.60; P = .0355). CONCLUSIONS: The platelet count of patients with malignant T2Es on POD 7 was definitively lower than that of patients with completed EVAR or with benign T2Es. The lower platelet count on POD 7 could be a risk factor for aneurysm sac enlargement among patients with T2Es.