Effect of gait speed on clinical outcomes after crural and pedal bypass in patients with chronic limb-threatening ischemia.

OBJECTIVES: Many factors affect long-term outcomes after open bypass in patients with chronic limb-threatening ischemia (CLTI). Ambulatory status has been suggested to be associated with clinical outcomes, but there is limited knowledge on the effect of gait speed on outcomes. The purpose of this study is to evaluate the effect of gait speed assessed in a 6-min walk test (6MWT) on outcomes after crural and pedal bypass in patients with CLTI. METHODS: A retrospective analysis was performed in patients with CLTI who underwent a 6MWT at 1 month after crural and pedal bypass at a single center from 2014 to 2021. Comparisons were made between those with high gait speed (HG group, 6-min walk distance (6MWD) > 288 m) and those with low gait speed (LG group, 6MWD ≤288 m). The primary endpoint was survival, and the secondary endpoints were graft patency, limb salvage, wound healing, major adverse cardiovascular events (MACEs), and hospital outcomes. RESULTS: Of 104 patients with CLTI who underwent a 6MWT after crural and pedal bypass, 46 (44%) and 58 (56%) were placed in the HG and LG groups, respectively. The LG group was older (p < .001), had more female subjects (p = .006), and had a higher prevalence of cerebrovascular disease (p = .042) and tissue loss (p = .007). The median follow-up was 36 (22-57) months. The HG group had significantly higher 3-year primary patency (65% vs 42%, p = .013), 3-year secondary patency (87% vs 66%, p = .018), 3-year overall survival (89% vs 58%, p < .001), and 3-year freedom from MACE (79% vs 67%, p = .039). The 3-year limb salvage and 12-month wound healing rates did not differ between the groups. CONCLUSIONS: Gait speed in patients with CLTI after crural and pedal bypass was associated with survival, freedom from MACE, and graft patency but not with limb salvage and wound healing. A detailed study of walking ability in these patients may be needed in the future.

Risk Analysis and Clinical Outcomes in Chronic Limb-threatening Ischemia Patients with Surgical Site Infection after Distal Bypass.

BACKGROUND: A recent randomized control study showed that long-term outcomes after surgical revascularization were superior to those after endovascular treatment for cases with chronic limb-threatening ischemia (CLTI) with an appropriate single-segment great saphenous vein. However, surgical site infection (SSI) in CLTI cases after infrapoplital bypass also resulted in a prolonged hospital stay and poor outcomes, including graft disruption. The aim of the current study was to analyze risk factors for SSI in CLTI patients after distal bypass and to compare outcomes in patients with and without SSI. METHODS: A total of 515 cases that underwent distal bypass at a single center between 2009 and 2022 were analyzed retrospectively. Comparisons were made between patients with and without SSI after distal bypass. The primary end point was limb salvage after distal bypass. RESULTS: Of the 515 cases that underwent distal bypass, 79 (15%) had SSI. The risk factors for SSI were preoperative antibacterial drug use (P = 0.001), pedal bypass (P = 0.001), and prolonged operation time (≥150 min) (P = 0.010). The median hospital stay in SSI cases was longer than that in non-SSI cases (P < 0.001). Of 515 distal bypasses, 7 (1.3%) bypass grafts ruptured postoperatively due to SSI, and of these 7 cases, 6 ruptured during the day, 5 cases occurred within 1 month postoperatively, and 2 patients (29%) are alive without amputation. The mean follow-up period was 34 ± 30 months. During follow-up, 62 limbs (SSI cases, 19; non-SSI cases, 43) required major amputation and there were 234 deaths (SSI cases, 46; non-SSI cases, 188). The 1-, 3-, and 5-year limb salvage rates of 82%, 71%, and 62%, respectively, in SSI cases were significantly lower than those in non-SSI cases (P < 0.001). The 5-year survival rate of 29% in SSI cases showed a tendency to be lower than that in non-SSI cases (P = 0.058). CONCLUSIONS: The limb salvage rate in SSI cases was lower than in non-SSI cases after distal bypass. Graft rupture due to SSI occurred at a rate of 1.3% and resulted in poor outcomes in most cases. SSIs adversely affect outcomes and further study is needed to identify methods to avoid SSI following distal bypass.

The effects of high quality team medicine on outcomes of chronic limb-threatening ischemia patients with infrapopliteal bypass.

OBJECTIVES: A team approach for treatment of patients with CLTI is used worldwide. However, the quality of team medicine is a concern. The Global Vascular Guidelines provide recommendations for high quality team medicine, but there is limited knowledge of the significance of team quality in CLTI treatment. The objective of this study is to evaluate the effects of team quality on clinical outcomes after infrapopliteal bypass. METHODS: A retrospective analysis was performed in 337 patients who underwent 414 infrapopliteal bypasses under a team medicine approach at a single center between 2009 and 2021. In 2017, team medicine was reorganized for improvement of quality. Comparisons were made between before (Group 1; 160 patients, 195 limbs) and after (Group 2; 177 patients, 219 limbs) reorganization. The primary endpoints were limb salvage and wound healing after infrapopliteal bypass. RESULTS: The patients included 227 males (67%) and had a median age of 76 [68-83] years. Diabetes mellitus was present in 67% and end-stage renal disease with hemodialysis in 37%. The follow-up rate was 96% in a mean follow-up period of 31±30 months. The 3-year limb salvage rate was significantly lower in Group 1 (before reorganization) than in Group 2 (after reorganization) (84% vs 95%, p = .001). The wound healing rates in the whole cohort were 72% at 6 months and 85% at 12 months, with no significant differences between the groups. In multivariate analysis, the risk factors for major amputation were treatment before reorganization (HR 2.68; p = .017), hemodialysis (HR 2.27; p = .017), and non-ambulatory status (HR 2.63; p = .005). CONCLUSIONS: A reorganized team approach with the goal of higher quality was independently associated with reduced major amputation for patients with CLTI treated with infrapopliteal bypass. This result indicates the importance of a high quality team approach for success of this treatment.

Limb outcomes based on limb severity and anatomic complexity following infrapopliteal vein bypass for Japanese patients with chronic limb-threatening ischemia.

OBJECTIVE: The 2019 Global Vascular Guidelines recommend a suitable initial revascularization method with reference to limb severity (wound, ischemia, and foot infection [WIfI] stage) and anatomic complexity (Global Limb Anatomical Staging System [GLASS] stage). However, limb outcomes after revascularization among WIfI and GLASS stages have not been investigated fully after infrapopliteal vein bypass. The purpose of this study was to assess the four Global Vascular Guideline-recommended limb outcomes after infrapopliteal vein bypass in cases with different WIfI and GLASS stages. METHODS: Patients who underwent infrapopliteal vein bypass for chronic limb-threatening ischemia at a single center were analyzed retrospectively. Medium-term limb outcomes were compared among WIfI and GLASS stages. The primary end points were limb salvage rate and major to minor amputation ratio, and the secondary end points were wound healing rate and wound healing time. RESULTS: A total of 353 infrapopliteal vein bypasses were performed in 284 patients with tissue loss (male, 193 patients; median age, 77 years; diabetes, 71%; hemodialysis, 41%). A total of 111 limbs (31%) required only minor amputation and 38 limbs (11%) required major amputation. The major to minor amputation ratio was 0.34 with no significant differences among WIfI stages or GLASS stages. The 3-year limb salvage rate was 87%. This rate was significantly lower in WIfI stage 4 than in stage 2 (P = .049), but did not differ significantly among GLASS stages. The 12-month wound healing rate was 86%. This rate was also significantly lower in WIfI stage 4 than in stages 2 and 3 (both P < .001), but did not differ significantly among GLASS stages. The median wound healing time was 55 days (range, 32-110 days), and was significantly longer in WIfI stage 4 compared with stages 2 (P = .001) and 3 (P < .001), but showed no significant differences among GLASS stages. CONCLUSIONS: The limb salvage rate, wound healing rate, and wound healing time were associated with limb severity (WIfI stage), but not with anatomic complexity (GLASS stage). These findings suggest that an appropriate preoperative strategy and careful perioperative management are important for patients with greater limb severity.

Effectiveness of the Vascular Quality Initiative Chronic Limb-Threatening Ischemia Mortality Prediction Model in Patents with Distal Bypass.

BACKGROUND: The purpose of this study is to evaluate the effectiveness of mortality prediction using the Vascular Quality Initiative (VQI) chronic limb-threatening ischemia (CLTI) model in patients with distal bypass. METHODS: Patients who underwent distal bypass for CLTI from 2009 to 2020 at a single center were retrospectively reviewed. Distal bypass was defined as any bypass with a distal anastomosis to the posterior tibial, anterior tibial, dorsalis pedis, plantar, or peroneal artery. Baseline characteristics, operative details, hospital outcomes, and medium-term outcomes were compared among patients with a low-, medium-, and high-risk of mortality based on a VQI CLTI calculation. The primary endpoints were survival and limb salvage. RESULTS: A total of 287 distal bypasses were performed in 230 patients (153 males; median age, 74 years; diabetes mellitus, 70%; end-stage renal disease [ESRD] with hemodialysis, 38%). These patients were stratified into 153 (66%) low-, 35 (15%) medium-, and 42 (18%) high-risk cases based on the VQI CLTI model. There were two hospital deaths (1%) within 30 days. During a mean follow-up period of 33 ± 29 months, 105 patients died and 26 limbs (9%) required major amputation. The 2-year survival rate of 81% in the low-risk group was significantly higher than those of 41% in the medium-risk group and 46% in the high-risk group (both P < 0.001). The 2-year survival rates did not differ significantly between the medium- and high-risk groups (P = 0.81). The 2-year limb salvage rate of 93% in the low-risk group was significantly higher than those of 81% in the medium-risk (P = 0.023) and those of 87% in the high-risk (P = 0.039) groups. There were no significant differences in graft patency and wound healing among the three groups. CONCLUSIONS: These results suggest that distal bypass is optimal treatment for patients with a low VQI-predicted risk of mortality. However, the lower limb salvage and higher mortality rates at 2 years suggest that the decision-making for VQI medium- and high-risk patients may be carefully considered.

Outcomes of a bypass-first strategy in chronic limb-threatening ischemia based on the Global Vascular Guidelines.

OBJECTIVE: The Global Vascular Guidelines (GVGs) recommend initial revascularization (bypass or endovascular therapy) for chronic limb-threatening ischemia (CLTI) based on anatomical complexity and limb severity. This decision is made based on a prediction of the outcomes after endovascular intervention. This study was performed to evaluate outcomes after distal bypass in cases recommended for GVG bypass. METHODS: A total of 239 distal bypasses for CLTI were evaluated in 195 patients with a GVG bypass recommendation treated between 2009 and 2020 at a single center in Japan. Comparisons were made between crural and pedal bypass cases. RESULTS: The 195 patients (median age, 77 years; 67% male) underwent 133 crural bypasses (106 patients; 54%) and 106 pedal bypasses (89 patients; 46%). Hemodialysis was more common in pedal cases than in crural cases (P = .03). Hospital deaths occurred in two cases (1%) within 30 days. The whole cohort has a follow-up rate of 96% over a mean of 28 ± 26 months, with 3-year limb salvage rates of 87% and 3-year primary, assisted primary, and secondary patency rates of 40%, 65%, and 67%, all without significant differences between crural and pedal cases. The 1-year wound healing rate was 88% and tended to be higher in crural cases than in pedal cases (P = .068). The 3-year survival rate was 52% in the cohort and did not differ significantly between crural and pedal cases. CONCLUSIONS: Patients with CLTI with a GVG bypass recommendation had acceptable limb salvage, graft patency, wound healing, and survival after distal bypass, regardless of the bypass method. These findings indicate that a GVG bypass recommendation as an initial revascularization method is valid in the real world.

An Evaluation of Pre-Operative Nutritional Assessment Methods in Patients with Chronic Limb Threatening Ischaemia Having Distal Bypass.

OBJECTIVE: The purpose of this study was to evaluate the influence of pre-operative nutritional status on long term outcomes of patients with chronic limb threatening ischaemia (CLTI) after distal bypass. METHODS: Patients who underwent distal bypass for CLTI from 2011 to 2020 at a single centre were reviewed retrospectively in Japan. Comparisons were made between patients with malnutrition and normal nutrition, as diagnosed by four nutritional assessments: Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), Glasgow Prognostic Score (GPS), and Prognostic Nutritional Index (PNI). The primary endpoint was survival, and the secondary endpoints were graft patency, limb salvage, and wound healing. RESULTS: A total of 314 distal bypasses were performed in 249 patients (169 males; median age, 76 years; diabetes mellitus, 70%; and end stage renal disease with haemodialysis, 40%). Malnutrition was observed in 103 patients (41%) evaluated by CONUT, 129 (52%) by GNRI, 76 (31%) by GPS, and 114 (46%) by PNI. The survival rates in the study cohort were 81% at one year, 55% at three years, and 47% at five years. Malnutrition in all assessments was statistically significantly associated with reduced survival rate (CONUT, p < .001; GNRI, p = .002; GPS, p < .001; PNI, p < .001). In multivariable analysis, CONUT was the best predictor of mortality (p = .014). Malnutrition did not affect graft patency and limb salvage, but malnutrition based on CONUT, GNRI, and GPS was statistically significantly associated with reduced wound healing (CONUT, p = .002; GNRI, p = .006; GPS, p = .011). In multivariable analysis, CONUT tended to be the best predictor of wound healing (p = .061). CONCLUSION: Malnutrition in patients with CLTI with distal bypass was associated with overall mortality and incomplete wound healing. CONUT assessment was most effective for prediction of survival and wound healing. Distal bypass for CLTI patients with malnutrition may be suboptimal, and endovascular treatment may be recommended as an initial revascularisation method.

Prognostic Significance of Intraoperative Graft Flow in Distal Bypass on Long-Term Outcomes in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: The aim of the study was to determine the prognostic significance of measurement of graft flow on the patency of distal bypass. METHODS: A retrospective analysis was performed for 208 distal bypasses (208 limbs, 170 patients) with a single segment great saphenous vein conducted in a nonreversed manner from January 2009 to December 2019 in Japan. Patient backgrounds, operative details (including intraoperative mean graft flow), hospital outcomes, and long-term outcomes were evaluated. The primary endpoints were the primary, assisted primary, and secondary patency of the distal bypass graft and the secondary endpoints were limb salvage and wound healing. RESULTS: The median intraoperative graft flow was 18 [10-30] mL/min. The follow-up rate was 98% in a mean follow-up period of 31 ± 26 months. Primary, assisted primary, and secondary patency in the cohort were 51%, 72%, and 73% at 1 year, and 39%, 59%, and 61% at 3 years, respectively. In multivariate analysis, the independent risk factors for primary patency were low graft flow (P = 0.0022) and female sex (P = 0.0016), and those for secondary patency were also low graft flow (P = 0.0025) and female sex (P < .001). The cut-offs for graft flow predicting primary and secondary patency were both 16 mL/min. The limb salvage rate was 94% at 1 year and 89% at 3 years; and the wound healing rates were 55%, 71% and 84% at 3, 6, and 12 months, respectively. Limb salvage and wound healing were not significantly associated with intraoperative graft flow. CONCLUSIONS: Intraoperative graft flow was an independent predictor for graft patency in distal bypass, but had no influence on limb salvage and wound healing. The cut-off value for the mean graft flow predicting primary and secondary patency was 16 mL/min.

Does the Global Limb Anatomic Staging System Inframalleolar Modifier Influence Long Term Outcomes of Chronic Limb Threatening Ischaemia after Distal Bypass?

OBJECTIVE: The purpose of this study was to evaluate the influence of inframalleolar disease (Global Limb Anatomic Staging System Inframalleolar [GLASS IM] modifier) on long term outcomes of patients with chronic limb threatening ischaemia (CLTI) after distal bypass. METHODS: Patients who underwent distal bypass for CLTI from January 2012 to December 2019 at a single centre were reviewed retrospectively. Comparisons including baseline characteristics, procedural details, and long term outcomes were made between patients with an intact pedal arch (GLASS IM modifier P0), an absent or severely diseased pedal arch (P1), and no target artery crossing the ankle into the foot (P2), diagnosed by pre- and intra-operative high quality angiography. The primary endpoint was limb salvage. The secondary endpoints were graft patency and wound healing. RESULTS: A total of 254 distal bypasses were performed in 206 patients (139 males; median age, 76 years). The GLASS IM modifier was P0 in 80 (32%) limbs, P1 in 127 (50%), and P2 in 47 (18%). During the follow up period, 22 limbs (9%) required major amputation. The limb salvage rates at three years in P0, P1, and P2 cases were 94%, 89%, and 93%, respectively, with no significant differences among the modifiers. The primary patencies at three years in P0, P1, and P2 cases were 49%, 38% and 24%, respectively. The primary patency in P2 cases was significantly lower than that in P0 cases (p < .050). The respective wound healing rates at 12 months were 97%, 93%, and 79%, and again the wound healing rate in P2 cases was significantly lower than those in other cases (p < .050). CONCLUSION: Long term outcomes including patency, limb salvage, and wound healing after distal bypass for CLTI patients with an infrapopliteal lesion were acceptable in cases in each GLASS IM modifier.

Effectiveness of combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass: A paradigm shift in surgical open bypass for chronic limb-threatening ischemia.

OBJECTIVES: The purpose of this study was to evaluate the results of combining superficial femoral artery endovascular therapy with distal bypass originating from the popliteal artery as a method of lower extremity revascularization in patients with chronic limb-threatening ischemia. METHODS: The records of patients undergoing combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass for chronic limb-threatening ischemia from January 2014 to April 2020 at a single institution were retrospectively reviewed. The patients' background, operative details, and long-term outcomes were analyzed. RESULTS: Fifty-two popliteal-to-distal bypasses with superficial femoral artery endovascular therapy were performed in 49 patients (33 men; mean age, 76 ± 9 years; diabetes mellitus, 80%; end-stage renal disease with hemodialysis, 47%). The Trans-Atlantic Inter-Society Consensus II classification of superficial femoral artery-popliteal lesion was "A" in 8 (15%) patients, "B" in 14 (27%) patients, "C" in 24 (46%) patients, and "D" in 6 (12%) patients. The intervention for superficial femoral artery lesions was plain old balloon angioplasty in 4 patients, self-expandable nitinol stent in 15 patients, drug-coated balloon in 18 patients, drug-eluting stent in 4 patients, stent graft in 10 patients, and interwoven nitinol stent in 1 patient. Distal bypass originated from the above-knee popliteal artery in 9 (17%) limbs and the below-knee popliteal artery in 43 (83%) limbs. The most common outflow artery was the posterior tibial artery (44%). The mean follow-up period was 17 ± 17 months. The primary and secondary patency of the graft was 44% and 72%, respectively, at 1 year and 39% and 72%, respectively, at 3 years. Primary patency and freedom from clinical-driven target lesion revascularization of superficial femoral artery endovascular therapy lesions were 85% and 90%, respectively, at 1 year and 63% and 75%, respectively, at 3 years. Limb salvage was 97% at 1 year and 92% at 3 years. Wound healing was 67% at 6 months and 83% at 12 months. CONCLUSIONS: Combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass may be a promising approach for patients with chronic limb-threatening ischemia because of durable patency, acceptable wound healing, and good limb salvage.

Long Term Outcomes of Endovascular Therapy for Failing Distal Bypass Vein Grafts.

OBJECTIVE: Although distal bypass using vein has been established with acceptable outcomes for chronic limb threatening ischaemia (CLTI), the major issue affecting long term outcomes is vein graft disease. This study aimed to analyse the peri-procedural results and long term outcomes of endovascular therapy (EVT) for failing vein grafts after distal bypass. METHODS: A retrospective analysis of 113 failing vein grafts (94 patients, 113 limbs) after distal bypass between 2009 and 2019 at the study hospital. RESULTS: The mean age was 74 ± 9 years and 72% of the patients were men. Of the 113 grafts, 54 grafts (48%) were detected in asymptomatic patients, 41 grafts (36%) in patients with recurrent ulcer or gangrene, and 18 grafts (16%) in patients with rest pain. The failing grafts were treated by low pressure long inflation balloon angioplasty with a mean balloon size of 3.0 ± 0.8 mm. The mean procedural time was 60 ± 29 min and procedural success was 98% (111 grafts). During the mean follow up period of 34 months, EVT was performed a median frequency of two times (range 1-11 times). The primary and assisted primary patency of the EVT revised grafts were 41% and 80% at one year, 34% and 68% at three years, 31% and 58% at five years, respectively. Of 41 limbs with recurrent ulcer or gangrene, the wound healed in 34 limbs (85%). The complete healing rate was 71% at three months and 84% at 12 months. Eight patients required major amputation, and the freedom from major amputation rate was 96% at one year and 80% at five years. CONCLUSION: Long term outcomes including patency, wound healing rate, and amputation free survival after EVT for failing vein grafts were acceptable. EVT could be a viable alternative to surgical revascularisation in patients with a failing distal bypass graft for CLTI.

Syntheses, Structures, and Antimicrobial Activities of Gold(I)- and Copper(I)- N-Heterocyclic Carbene (NHC) Complexes Derived from Basket-Shaped Dinuclear Ag(I)-NHC Complex.

Novel dinuclear gold(I)- and copper(I)- N-heterocyclic carbene (NHC, L-1a) complexes [M2(L-1a)](PF6)2 (M = AuI (Au-1·PF6) and M = CuI (Cu-1·PF6)) were synthesized by transmetalation of the dinuclear silver(I)-NHC complex [Ag2(L-1a)](PF6)2 (Ag-1·PF6) with [AuCl(Me2S)] or CuI in over 70% yield. These NHC complexes were characterized by CHN elemental analysis, Fourier transform infrared spectroscopy, thermogravimetry/differential thermal analysis, and solution (1H and 13C) NMR spectroscopy. X-ray crystallography revealed that Au-1·PF6 and Cu-1·PF6 are dinuclear molecules consisting of two linear intramolecular C-M-C bonds (M = AuI and CuI), one M···M interaction, and two metal atoms arranged in a T-shaped geometry; their molecular structures are very similar to the basket-shaped cage structure of the parent complex Ag-1·PF6. Because of the smaller ionic radius of copper(I), Cu-1·PF6 has the smallest upper space of the basket among the three complexes. Au-1·PF6 and Cu-1·PF6 were very stable in the solid state and in solution. They did not undergo nucleophilic reaction with thiols 2-mercaptoethanol and 2-benzimidazolethiol (Hbmt) at least for several hours, whereas Ag-1·PF6 did react, forming precipitates of silver(I) thiolate and the free ligand L-1a·PF6. The minimum inhibitory concentration values toward a panel of bacteria, yeasts, and molds were examined in a water-suspension system and a solution system containing dimethyl sulfoxide. The antimicrobial spectra of the three compounds were metal-dependent, and Au-1·PF6 showed the greatest activity toward Gram-positive bacteria.