Chronic Limb-Threatening Ischemia is a Residual Bleeding Risk Factor among Patients with Lower Extremity Artery Disease.

AIM: Lower-extremity artery disease (LEAD) is a high-risk factor for bleeding. However, the specific risk factors for bleeding in patients with LEAD remain unclear. We aimed to identify risk factors for bleeding in patients with LEAD after endovascular treatment (EVT). METHODS: This multicenter, retrospective, observational study included 732 consecutive patients with LEAD who underwent EVT between January 2018 and December 2019. Patient characteristics, laboratory data, target lesions, and medications were compared between patients with and without chronic limb-threatening ischemia (CLTI). Predictive bleeding risk factors were explored using Cox regression analysis with differential models. RESULTS: In model 1, a body mass index (BMI) ＜18.5 kg/m2, prior heart failure, high bleeding risk, use of single antiplatelet therapy (SAPT) plus warfarin, and CLTI were predictive bleeding risk factors (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.13-3.52; p＜0.01; HR 2.15; 95% CI 1.28-3.55; p＜0.01; HR 3.40; 95% CI 1.28-3.55; p＜0.01; HR 2.05; 95% CI 1.33-5.84; p＜0.01; respectively). In model 2, a BMI ＜18.5 kg/m2, prior heart failure, anemia (＜11 g/dL), low platelet count (＜10*104/µL), chronic kidney disease, use of single antiplatelet therapy (SAPT) plus warfarin, and CLTI were independent risk factors for bleeding (model 2: HR 2.05; 95% CI 1.12-3.56; p=0.02; HR 2.35; 95% CI 1.39-3.90; p＜0.01; HR 2.71; 95% CI 1.64-4.50; p＜0.01; HR 2.66; 95% CI 1.00-5.89; p=0.05; HR 2.47; 95% CI 1.25-5.45; p＜0.01; HR 2.79; 95% CI 1.24-5.63; p=0.01; respectively) Conclusions: CLTI is a residual and predictive risk factor for bleeding in patients with LEAD. We have to pay attention to the bleeding events of patients with CLTI after EVT during follow-up.

Validation of the Usefulness of the Diameter Reduction, Spiral Shape, Flow Impairment, or Adverse Morphology Classification System in Real-World Clinical Practice.

AIM: The accuracy of the DISFORM (diameter reduction, spiral shape, flow impairment, or adverse morphology) classification system has not been validated. METHODS: This retrospective multicenter observational study enrolled 288 consecutive patients with lower extremity artery disease who underwent endovascular therapy with drug-coated balloons for femoropopliteal lesions between January 2018 and December 2021. Patients were classified into DISFORM I-IV groups. Primary patency (PP) and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months, and recurrence predictors at 12 months were investigated. RESULTS: In total, 183, 66, 11, and 28 patients were classified into DISFORM I, II, III, and IV groups, respectively. In the DISFORM I, II, III, and IV groups, the PP rates were 75.3%, 91.1%, 87.5%, and 50.0%, respectively, and freedom from CD-TLR rates were 86.0%, 91.6%, 88.9%, and 76.7%, respectively, at 12 months. In the DISFORM I-III and IV groups, the PP rates were 79.4% and 50.0%, respectively, and freedom from CD-TLR rates were 87.5% and 76.7%, respectively, at 12 months. Multivariate analysis showed that chronic limb-threatening ischemia, DISFORM IV, and Lutonix™ use were independent predictors of PP loss at 12 months. CONCLUSION: DISFORM IV had a lower PP rate than DISFORM I-III in midterm phase.

Predictors of recurrence based on intravascular ultrasound findings after Eluvia placement in symptomatic peripheral arterial disease: A retrospective study.

Background and Aims: Polymer-coated drug-eluting stents (Eluvia) have shown favorable clinical outcomes in real-world registries. There are no reports on recurrent predictors after Eluvia placement based on intravascular ultrasound (IVUS) findings. Methods: We analyzed clinical data from the ASIGARU PAD registry, a retrospective, multicenter, observational study that enrolled patients who underwent endovascular therapy for superficial femoral and proximal popliteal arteries lesions using Eluvia or drug-coated balloon. The primary outcome was the identification of recurrent predictors, including IVUS parameters at 12 months. The rate of target lesion recurrence was also assessed. Results: IVUS images were obtained in 54 of 65 cases. Seven recurrent cases (13.0%) were observed within 12 months. The random survival forest method presented eight predictive variables of recurrence: Clinical Frailty Scale (CFS), distal stent edge area, distal plaque burden, age, sex, distal external elastic membrane (EEM) area, minimum stent area (MSA), and distal lumen area. Furthermore, the partial dependence plot showed that frailty (CFS ≥ 6), smaller distal stent edge area, higher and lower distal plaque burden, older and younger age, female sex, smaller distal EEM area, smaller MSA, and smaller and larger distal lumen area predicted recurrence after Eluvia placement within 12 months. Conclusion: CFS, distal stent edge area, distal plaque burden, age, sex, distal EEM area, MSA, and distal lumen area were significant recurrent predictors after Eluvia placement.

Clinical Outcomes Based on High Bleeding Risk in Patients With Lower Extremity Peripheral Artery Disease Who Have Undergone Endovascular Therapy.

PURPOSE: Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. In this study, we investigated the prevalence and severity of HBR, as well as its association with clinical outcomes in the patients with PAD who underwent EVT. MATERIALS AND METHODS: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria were applied to 732 consecutive patients with lower extremity PAD post-EVT to assess the prevalence of HBR, and its association with major bleeding events, all-cause mortality, and ischemic events. The ARC-HBR scores (1 point for each major criterion and 0.5 points for each minor criterion) were obtained and the patients were divided into four groups (score: 0-0.5; low risk, score: 1-1.5; moderate risk, score: 2-2.5; high risk, and score: ≥3; very high risk) according to the score. Major bleeding events were defined as Bleeding Academic Research Consortium type-3 or type-5 bleeding, and ischemic events were defined as the composite of myocardial infarction, ischemic stroke, and acute limb ischemia within 2 years. RESULTS: High bleeding risk occurred in 78.8% of the patients. Major bleeding events, all-cause mortality, and ischemic events occurred in 9.7%, 18.7%, and 6.4% of the study cohort, respectively, within 2 years. During the follow-up period, major bleeding events significantly increased with the ARC-HBR score. The severity of the ARC-HBR score was significantly associated with an increased risk of major bleeding events (high risk: adjusted hazard ratio [HR] 5.62; 95% confidence interval [CI]: [1.28, 24.62]; p=0.022; very high risk: adjusted HR: 10.37; 95% CI: [2.32, 46.30]; p=0.002). All-cause mortality and ischemic events also significantly increased with higher ARC-HBR score. CONCLUSIONS: High bleeding risk patients with lower extremity PAD can be at a high risk of bleeding events, mortality, and ischemic events after EVT. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with lower extremity PAD who undergo EVT. CLINICAL IMPACT: Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. Post EVT, most of the patients with PAD were classified as having HBR using the Academic Research Consortium for HBR (ARC-HBR) criteria and the rate of bleeding events as well as mortality and ischemic events within 2 years increased as the ARC-HBR score increased in this retrospective study of 732 participants. HBR patients with PAD can be at high risk of not only bleeding events but also mortality and ischemic events in the mid-term. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with PAD who underwent EVT.

Association between High Bleeding Risk and 2-Year Mortality in Patients with Chronic Limb-Threatening Ischemia.

AIM: Patients with chronic limb-threatening ischemia (CLTI) have a high bleeding risk (HBR) and mortality rate. The 2-year life expectancy is an important factor in deciding the appropriate treatment strategy. This study aimed to assess the influence of HBR on the prognosis of patients with CLTI. METHODS: A total of 259 patients with CLTI who underwent endovascular therapy (EVT) (mean age, 76.2 years; male, 62.9%) between January 2018 and December 2019 were evaluated. The Academic Research Consortium for HBR (ARC-HBR) criteria were applied to each patient, and the ARC-HBR scores were calculated. The cut-off score for predicting all-cause mortality within two years was derived using a survival classification and regression tree (CART) model. Causes of death and the association between ARC-HBR scores and major bleeding events within two years were also investigated. RESULTS: Based on the CART model, patients were divided into three groups (low HBR score 0-1.0, 48 patients; moderate HBR score 1.5-3.0, 176 patients; and high HBR score ≥ 3.5, 35 patients). During the study period, 82 patients (39.6%) died due to cardiac (n=23) and non-cardiac causes (n=59). All-cause mortality increased significantly with increasing ARC-HBR scores. Cox multivariate analysis revealed a significant association between high ARC-HBR scores and the risk of all-cause mortality within two years. Major bleeding events increased significantly with increasing ARC-HBR scores. CONCLUSIONS: The ARC-HBR score could predict 2-year mortality in patients with CLTI who underwent EVT. Thus, this score can help determine the best revascularization strategy for patients with CLTI.

Two-year clinical outcomes and predictors of restenosis following the use of polymer-coated paclitaxel-eluting stents or drug-coated balloons in patients with femoropopliteal artery disease.

We aimed to assess the clinical performance and risk factors for patency loss within 2 years following the use of polymer-coated paclitaxel-eluting stents (PC-PESs) and drug-coated balloons (DCBs) in patients with lower extremity artery disease. Multi-center registry data from 151 patients (65 and 86 treated with PC-PES and DCB, respectively) were retrospectively investigated. Two-year primary patency (PP) and clinically driven target lesion revascularization (CD-TLR) were evaluated using Kaplan-Meier analysis. Predictors of restenosis within 2 years of the procedures were analyzed using the random survival forest method. The consistent predictors of restenosis within 1 and 2 years were assessed and validated using Kaplan-Meier analysis. Two-year PP was 77.2 and 57.2% (log rank p = 0.047) and freedom from CD-TLR was 84.4 and 84.8% in the PC-PES and DCB groups, respectively (log rank p = 0.89). In the DCB group, most of the patients (n = 77, 89.5%) were treated with high-dose DCB. Consistent predictors of restenosis were lower vessel diameter and severity of Clinical Frailty Scale in the PC-PES group, and severity of peripheral artery calcification scoring system grade, severity of post dissection pattern, and smaller vessel diameter in the DCB group. The validation analysis revealed that patients with consistent predictors had significantly worse PP values than that of those without in the PC-PES (87.9% vs. 55.3%, log rank p = 0.003) and DCB groups (75.9% vs. 35.2%, log rank p = 0.001). The 2-year PP of DCBs was lower than that of PC-PESs. A smaller vessel diameter could predict restenosis in both devices. Vessel calcification and dissection should be considered when using DCB to ensure longer term patency.

Staphylococcus aureus Infection-Related Glomerulonephritis with Dominant IgA Deposition.

Since 1995, when we reported the case of a patient with glomerulonephritis with IgA deposition that occurred after a methicillin-resistant Staphylococcus aureus (MRSA) infection, many reports of MRSA infection-associated glomerulonephritis have accumulated. This disease is being systematized as Staphylococcus infection-associated glomerulonephritis (SAGN) in light of the apparent cause of infection, and as immunoglobulin A-dominant deposition infection-related glomerulonephritis (IgA-IRGN) in light of its histopathology. This glomerulonephritis usually presents as rapidly progressive glomerulonephritis or acute kidney injury with various degrees of proteinuria and microscopic hematuria along with an ongoing infection. Its renal pathology has shown several types of mesangial and/or endocapillary proliferative glomerulonephritis with various degrees of crescent formation and tubulointerstitial nephritis. IgA, IgG, and C3 staining in the mesangium and along the glomerular capillary walls have been observed on immunofluorescence examinations. A marked activation of T cells, an increase in specific variable regions of the T-cell receptor ß-chain-positive cells, hypercytokinemia, and increased polyclonal immune complexes have also been observed in this glomerulonephritis. In the development of this disease, staphylococcal enterotoxin may be involved as a superantigen, but further investigations are needed to clarify the mechanisms underlying this disease. Here, we review 336 cases of IgA-IRGN and 218 cases of SAGN.

Recurrent Mural Thrombosis of the Ascending Aorta in a Patient with Antiphospholipid Syndrome.

A 38-year-old man presented with embolic occlusion of the brachial artery. As per his computed tomography results, a pedunculated mass in the proximal ascending aorta was detected. Since discrimination between a thrombus and a tumor was deemed difficult, the patient underwent replacement of the ascending aorta. Histopathology revealed the mass to be a thrombus. The diagnosis of antiphospholipid syndrome was then confirmed postoperatively. Six months post-surgery, a new thrombus was detected in the vascular prosthesis. The thrombus resolved after treatment with edoxaban and aspirin. To the best of our knowledge, this is the first report on graft thrombosis in antiphospholipid syndrome, highlighting the importance of seamless anticoagulation therapy.

Impact of Serum Zinc Level and Oral Zinc Supplementation on Clinical Outcomes in Patients Undergoing Infrainguinal Bypass for Chronic Limb-Threatening Ischemia.

BACKGROUND: Zinc (Zn) has been reported to play an important role in wound healing (WH). Nevertheless, the effect of Zn in chronic limb-threatening ischemia (CLTI) patients is unclear. This study investigated the effect of Zn on the clinical outcomes of CLTI patients undergoing bypass surgery.Methods and Results: This study reviewed 111 consecutive patients who underwent an infrainguinal bypass from 2012 to 2020. Patients with Zn deficiency (serum Zn level <60 µg/dL) received oral Zn supplementation and maintained a normal level until WH. This study aimed to explore: (1) the effect of Zn deficiency; and (2) Zn supplementation in Zn-deficient patients on the clinical outcomes of this cohort. Patients with Zn deficiency, Zn supplementation, and no Zn supplementation despite Zn deficiency accounted for 48, 21, and 42 patients, respectively. (1) Zn deficiency was associated with WH (HR, 0.47; 95% CI, 0.29-0.78: P=0.003), major adverse limb events (MALE) (HR, 2.53; 95% CI, 1.26-5.09: P=0.009), and major amputation or death (HR, 3.17; 95% CI, 1.51-6.63: P=0.002). (2) Zn supplementation was positively related to WH (HR, 2.30; 95% CI, 1.21-4.34: P=0.011). This result was confirmed using propensity score matching (HR, 2.24; 95% CI, 1.02-4.87: P=0.043). CONCLUSIONS: The current study revealed that Zn level was associated with clinical outcomes in CLTI patients after bypass surgery. Oral Zn supplementation could improve WH in these patients.

Comparison of clinical outcomes, including the wound healing rate, between inframalleolar bypass to the pedal artery and that to the pedal branch artery in the modern endovascular era.

OBJECTIVE: Inframalleolar (IM) bypass has been reported to demonstrate acceptable patency and limb salvage in patients with chronic limb-threatening ischemia. However, wound healing after IM bypass and comparisons between pedal artery (PA) bypass and pedal branch artery (PBA) bypass are lacking. METHODS: We reviewed prospectively collected data from 208 consecutive patients after IM bypass performed over a period of 6 years. Patients were divided into two groups based on the distal anastomotic artery: the PA group (dorsal pedis artery or common plantar artery) and the PBA group (medial tarsal, lateral tarsal, medial plantar, and lateral plantar artery). The primary outcome was wound healing, and secondary outcomes included loss of patency and limb and life prognosis. RESULTS: Of the 208 patients, 174 (74%) had PA bypass, whereas 34 (16%) had PBA bypass. Patients in the PBA group were significantly younger than those in the PA group (69 ± 7 vs 73 ± 9; P = .03). Although early (30-day) graft failure was more common in the PBA group, late clinical outcomes, including the wound healing rate (79% in the PA group and 84% in the PBA group; P = .74), were similar between the two groups. The Global Limb Anatomic Staging System IM grade (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.58-0.93; P = .006); wound, ischemia, and foot infection wound grade (HR, 0.67; 95% CI, 0.51-0.89; P < .01); and wound, ischemia, and foot infection foot infection grade (HR, 0.79; 95% CI, 0.65-0.96; P = .02) were independent predictors of wound healing. CONCLUSIONS: The current study revealed that wound healing in patients after PBA bypass was acceptable and comparable with that after PA bypass. In the modern era, including a high prevalence of infrapopliteal angioplasty, our results could provide useful information to clinicians in actual clinical settings. Moreover, PBA bypass may be an alternative revascularization procedure to avoid major amputation when the PA is occluded, such as in the global vascular guideline IM P2 grade. Prospective multicenter larger studies are warranted to confirm the findings of this study and to compare PBA bypass and IM endovascular treatment in patients with anatomical no-option chronic limb-threatening ischemia.

Zinc deficiency impairs ischemia-induced angiogenesis.

OBJECTIVE: Zinc is an important essential trace metal involved in many physiologic functions, and its deficiency can affect the development of multiple organs, including the vasculature. However, clarity is lacking regarding the effects of zinc deficiency in the regulation of angiogenesis. We investigated the effects of zinc deficiency on the revascularization process through animal experiments and examined the relationship between the circulating zinc levels and tissue blood perfusion in patients with chronic limb-threatening ischemia (CLTI). METHODS: Zinc-deficient mice and control wild-type mice had undergone surgery to create unilateral hindlimb ischemia. Next, we examined the relationship between the serum zinc levels and skin perfusion pressure (SPP) as an index of tissue blood perfusion in patients with CLTI. A total of 51 patients with CLTI who had been referred for de novo revascularization for CLTI due to arteriosclerosis obliterans at our hospital from May 2012 to March 2016 were enrolled. RESULTS: The zinc-deficient mice showed a significant reduction in blood flow recovery rates in the ischemic limb and capillary density in the ischemic adductor muscle fibers compared with the control wild-type mice. The zinc-deficient mice also showed increased reactive oxygen species production after hindlimb ischemia. Nicotinamide adenine dinucleotide phosphate oxidase inhibitors ameliorated the zinc deficient-induced impairment of revascularization. The serum zinc levels were positively associated with the SPP in the CLTI patients. Multivariate regression analysis also revealed that the serum zinc levels were significantly correlated with the SPP in patients with CLTI. CONCLUSIONS: Zinc deficiency impaired the rate of ischemia-induced revascularization through enhanced oxidative stress rates, suggesting that nutritional management for zinc sufficiency could be useful in CLTI prevention and treatment.

Clinical outcomes and predictors of restenosis in patients with femoropopliteal artery disease treated using polymer-coated paclitaxel-eluting stents or drug-coated balloons.

Both polymer-coated paclitaxel-eluting stents (PC-PESs) and drug-coated balloons (DCBs) are used in conjunction with endovascular therapy (EVT) for the treatment of peripheral artery disease (PAD). We aimed to identify the risk factors for the loss of patency following the use of PC-PES and DCB in a real clinical setting. We assessed the multi-center registry data of 151 lesions from 151 patients who underwent EVT for symptomatic PAD in the superficial femoral and proximal popliteal arteries using PC-PES or DCB. One-year primary patency (PP) and clinically driven target lesion revascularization (CD-TLR) were evaluated using Kaplan-Meier analysis. The predictive risk factors for 1-year outcomes were analyzed using the random survival forest method. PC-PES and DCB were used in 65 (43.0%) and 86 (57.0%) cases, respectively. There were no significant differences in 1-year PP or freedom from CD-TLR between PC-PES and DCB. PP occurred in 85.4% and 80.2% of cases in the PC-PES and DCB groups, respectively (log-rank p = 0.65), while freedom from CD-TLR was noted in 92.7% and 94.1% of cases in the PC-PES and DCB groups, respectively (log-rank p = 0.73). In order of importance, a Clinical Frailty Scale score ≥ 6, female sex, lower proximal vessel diameter, lower body mass index, and younger and older age were identified as predictive risk factors of restenosis in the PC-PES group. Peripheral artery calcification scoring system grade of ≥ 2, post-dissection pattern ≥ D, lower proximal and distal vessel diameter, and lesion length ≥ 100 mm were identified as predictive risk factors of restenosis, in order of importance, in the DCB group. Both PC-PES and DCB were associated with favorable clinical outcomes within 1 year in patients with femoropopliteal artery disease. Furthermore, several factors that could predict restenosis within 1 year following the use of each device were detected.

Patterns in Psychiatrists' Prescription of Valproate for Female Patients of Childbearing Age With Bipolar Disorder in Japan: A Questionnaire Survey.

BACKGROUND: Accumulating evidence has shown that valproate has the greatest teratogenic potential for increasing the risk of major congenital malformations, such as neural tube defects, cleft palate, and neurodevelopmental disability. Although valproate is a pharmacological option for acute mania and is used as a stabilization drug for patients with bipolar disorder, some global guidelines state that valproate should not be used for girls or women of childbearing age with bipolar disorder. We investigated patterns in psychiatrists' prescription of valproate for bipolar female patients of childbearing age in Japan. METHODS: From March to May 2018, we conducted a questionnaire survey among psychiatrists from all prefectures in Japan on psychiatric practice as it relates to major depression and bipolar disorder throughout women's life. The questionnaire had two parts: (1) assessment of participating psychiatrists' backgrounds and attitudes toward patients and (2) their patterns of prescription of psychotropics for female patients with mood disorders across generations and periods of pregnancy. Each question item had four response options: "not at all," "rarely," "sometimes," and "frequently." We examined patterns of prescription for childbearing-aged women (late adolescence/young adulthood aged 18-24 years, childbearing-age, older adults aged 25-49 years) and pregnant women. RESULTS: In total, 571 psychiatrists (427 males, 123 females, and 21 unknowns) responded appropriately to the questionnaire, including 320 who examined at least one or more late adolescence/young adulthood bipolar women. Approximately 70% of psychiatrists answered that they frequently or sometimes prescribed valproate for bipolar women of childbearing age [late adolescence/young adulthood: not at all, n = 23 (7.5%); rarely, n = 69 (22.5%); sometimes, n =116 (37.8%); and frequently, n = 99 (32.2%); childbearing-age, older adults: not at all, n = 13 (2.7%); rarely, n = 67 (13.8%); sometimes, n = 185 (38.1%); and frequently, n = 220 (45.4%)]. The proportion of general hospital psychiatrists who answered "not at all" or "rarely" to the frequency of their valproate prescriptions was higher than that of psychiatrists working in other medical facilities (χ 2(3) = 18.2, p < 0.001). CONCLUSION: Most psychiatrists frequently or sometimes prescribe valproate for women of childbearing age in Japan.

Zinc Deficiency and Clinical Outcome After Infrainguinal Bypass Grafting for Critical Limb Ischemia.

Background: The aim of this study was to identify a relationship between zinc (Zn) deficiency and clinical outcome in patients with critical limb ischemia (CLI). Methods and Results: Forty-five limbs from 44 patients with CLI who underwent de novo infrainguinal bypass grafting (IBG) were retrospectively reviewed. The patients were divided into a Zn deficiency group (ZD group: Zn <60 µg/dL) and a Zn sufficiency group (ZS group: Zn ≥60 µg/dL). Graft patency, limb salvage (LS), amputation-free survival (AFS), and wound healing were compared between the groups. LS and AFS were examined to identify whether Zn deficiency was an independent predictor. The preoperative factors potentially predictive of Zn deficiency were also analyzed. Twenty-four limbs were categorized into the ZD group. Patients in the ZD group were more likely to have undergone hemodialysis (HD) and have lower serum albumin. The surgical procedures were not significantly different between the groups. Patency, LS, AFS, and complete wound healing rates were significantly lower in the ZD group. Zn deficiency was a negative predictor of LS. Age >75 years and HD were identified as predictors of Zn deficiency. Conclusions: Zn deficiency was associated with poor clinical outcome. Zn supplementation may improve clinical outcomes during IBG for CLI.

Association Between Preoperative Frailty and Mortality in Patients With Critical Limb Ischemia Following Infrainguinal Bypass Surgery　- Usefulness of the Barthel Index.

BACKGROUND: Most patients with critical limb ischemia (CLI) exhibit severe comorbidities accompanied by frailty. This study assessed and risk-stratified mortality after infrainguinal bypass (IB) in CLI and investigated the effects of frailty.Methods and Results:The study retrospectively reviewed 107 consecutive CLI patients who had undergone de novo IB due to atherosclerotic disease. Data regarding patient age, comorbidities, laboratory data, and functional status were collected; functional status was evaluated using the Barthel index (BI) and nutritional status was evaluated using albumin concentrations and body mass index (BMI). Mean (±SD) BI and BMI were 75±16 and 22±4 kg/m2, respectively. BI (hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.94-0.99, P=0.004), BMI (HR 0.85; 95% CI 0.75-0.95, P=0.003), atrial fibrillation (AF; HR 5.31; 95% CI 2.12-13.30, P<0.001), and ejection fraction (EF; HR 0.94; 95% CI 0.91-0.98, P=0.003) were independent predictors of mortality. Patients were divided into 2 groups based on BI (BI >75, n=71; and BI <70, n=36). Survival after IB was significantly lower for the lower BI group (P<0.001, log-rank test). After propensity score matching, post-IB survival remained significantly lower in the lower BI group (P=0.02). CONCLUSIONS: BI, BMI, AF, and EF were independently associated with all-cause mortality after IB for CLI. BI and BMI may be useful in identifying and optimizing treatment for high-risk frail patients.

Long-term Comparison of Endovascular and Open Repair of Abdominal Aortic Aneurysms: Retrospective Analysis of Matched Cohorts with Propensity Score.

BACKGROUND: Although recent guidelines recommend endovascular aneurysm repair (EVAR) for robust younger patients, we have been limiting our indication to older patients or those who are physically frail. This study compares long-term outcomes of our series of abdominal aortic aneurysms (AAAs) treated with endovascular repair (ER) and open surgery (OS), using propensity score matching. METHODS: Between June 2007 and October 2014, 819 patients with infrarenal AAA underwent elective repair at our institution. Among them, 737 patients (386 ERs and 351 OSs) with over 1-year follow-up or any events (reintervention or mortality) were enrolled. Covariates for matching included age, sex, hypertension, coronary arterial disease, obstructive pulmonary disease, diabetes, stroke, malignancy, hemodialysis, ejection fraction, serum creatinine, and respiratory function. RESULTS: After propensity score matching, 157 pairs were selected. In the original cohort, overall survival at 5 years was 84.1% in ER and 89.3% in OS; the difference was significant (P = 0.019). The freedom-from-reintervention rates at 5 years were also significantly different, 81.8% in ER and 92.8% in OS (P = 0.007). In the matched cohort, age and comorbidities were similar both in ER and OS. The overall survival at 5 years was 85.4% and 90.1% in ER and OS, respectively; the difference was not significant (P = 0.242). The freedom-from-reintervention rates at 5 years were 81.1% in ER and 89.1% in OS; these were also not significantly different (P = 0.178). CONCLUSIONS: Risk-adjusted comparisons revealed that long-term outcomes of ER and OS were comparable among our relatively frail patients in their age 70s. Our results failed to show the long-term advantage of EVAR in rather high-risk patients and provided no supportive evidence for our selection criteria.

Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome.

BACKGROUND: We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS). METHODS: Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (C max) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR. RESULTS: At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan-Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 µg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration. CONCLUSION: Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine C max, and more than 1.1 µg/mL of C max is necessary for CR.