Prognostic factors after open and endovascular repair for infective native aneurysms of the abdominal aorta and common iliac artery.

OBJECTIVE: Infective native aneurysms (INAs) of the abdominal aorta and iliac arteries are uncommon, but potentially fatal. Endovascular aneurysm repair (EVAR) has recently been introduced as a durable treatment option, with outcomes comparable to those yielded by conventional open repair. However, owing to the rarity of the disease, the strengths and limitations of each treatment remain uncertain. The present study aimed to separately assess post-open repair and post-EVAR outcomes and to clarify factors affecting the short-term and late prognosis after each treatment. METHODS: Using a nationwide clinical registry, we investigated 600 patients treated with open repair and 226 patients treated with EVAR for INAs of the abdominal aorta and/or common iliac artery. The relationships between preoperative or operative factors and postoperative outcomes, including 90-day and 3-year mortality and persistent or recurrent aneurysm-related infection, were examined. RESULTS: Prosthetic grafts were used in >90% of patients treated with open repair, and in situ and extra-anatomic arterial reconstruction was performed in 539 and 57 patients, respectively. Preoperative anemia and imaging findings suggestive of aneurysm-enteric fistula were independently associated with poor outcomes in terms of both 3-year mortality (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.62; P = .046, and HR, 2.24; 95% CI, 1.12-4.46; P = .022, respectively) and persistent or recurrent infection (odds ratio [OR], 2.16; 95% CI, 1.04-4.49; P = .039, and OR, 4.96; 95% CI, 1.81-13.55; P = .002, respectively) after open repair, whereas omental wrapping or packing and antibiotic impregnation of the prosthetic graft for in situ reconstruction contributed to improved 3-year survival (HR, 0.60; 95% CI, 0.39-0.92; P = .019, and HR, 0.53; 95% CI, 0.32-0.88; P = .014, respectively). Among patients treated with EVAR, abscess formation adjacent to the aneurysm was significantly associated with the occurrence of persistent or recurrent infection (OR, 2.24; 95% CI, 1.06-4.72; P = .034), whereas an elevated preoperative white blood cell count was predictive of 3-year mortality (HR, 1.77; 95% CI, 1.00-3.13; P = .048). CONCLUSIONS: Profiles of prognostic factors differed between open repair and EVAR in the treatment of INAs of the abdominal aorta and common iliac artery. Open repair may be more suitable than EVAR for patients with concurrent abscess formation.

Effects of SGLT2 Inhibitors and DPP-4 Inhibitors on Advanced Glycation End Products.

Clinical trials have revealed that sodium glucose cotransporter 2 (SGLT2) inhibitors suppress the onset of heart failure and cardiovascular death in diabetic patients. On the other hand, few reports have been published concerning such effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. We undertook the present study to evaluate the effects of SGLT2 inhibitors and DPP-4 inhibitors on the advanced glycation end products (AGEs), well known as a risk factor for the development of cardiovascular disorders.Type 2 diabetes mellitus were divided into two groups and treated with either SGLT2 inhibitors or DPP-4 inhibitors for 3 months. Before and after the 3-month treatment period with each drug, the AGEs and diabetes-related parameters were measured. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured as one of the AGEs.In the SGLT2 inhibitor group, both the blood HbA1c and MG-H1 levels decreased significantly after the 3-month treatment period. In the DPP-4 inhibitor group, only the blood HbA1c level decreased significantly, with no significant change of the blood MG-H1 level.SGLT2 inhibitor reduced both the blood levels of HbA1c and AGEs (MG-H1). Considering that the blood levels of AGEs are associated with the risk of heart failure and cardiovascular disorders, the results of the present study suggest that the effect of SGLT2 inhibitors in suppressing cardiovascular death might be mediated by the reduction in the blood levels of AGEs induced by this class of drugs. DPP-4 inhibitors showed no significant effects on the blood levels of AGEs.

Effects of SGLT2 inhibitors on the intestinal bacterial flora in Japanese patients with type 2 diabetes mellitus.

Selective inhibitors of sodium glucose co-transporter-2 (SGLT2) suppress renal glucose reabsorption and promote urinary glucose excretion, thereby lowering blood glucose. SGLT2 inhibitors have been reported to reduce body weight. However, the mechanism underlying the reduction in the body weight induced by SGLT2 inhibitor treatment remains to be elucidated. In this study, we investigated the effects of SGLT2 inhibitors on the intestinal bacterial flora. A total of 36 Japanese patients with type 2 diabetes mellitus received a SGLT2 inhibitor (luseogliflozin or dapagliflozin) for 3 months, and the prevalences of balance-regulating bacteria and balance-disturbing bacteria in the feces of the patients before and after SGLT2 inhibitor treatment were determined. SGLT2 inhibitor treatment was associated with a significant increase of the overall prevalence of the 12 types of balance-regulating bacteria. In addition, significant increases in the prevalences of the short-chain fatty acid (SCFAs)-producing bacteria among the balance-regulating bacteria were also observed. Individual analyses of the balance-regulating bacteria revealed that the SGLT2 inhibitor treatment was associated with a significant increase in the prevalence of Ruminococci, which are balance-regulating bacteria classified as SCFAs-producing bacteria. However, SGLT2 inhibitor had no effect on the balance-disturbing bacteria. These results suggested that SGLT2 inhibitor treatment was associated with an overall increase in the prevalence of balance-regulating bacteria. Among the balance-regulating bacteria, the prevalences of SCFAs-producing bacteria increased. SCFAs have been reported to prevent obesity. The results of the present study suggest that SGLT2 inhibitors might induce body weight reduction via their actions on the intestinal bacterial flora.

Surgical Treatment for Popliteal Artery Entrapment Syndrome in Japan: a Retrospective, Multicentre Study Using a National Clinical Registry.

OBJECTIVE: Surgical treatment is an established method for popliteal artery entrapment syndrome (PAES), which, however, mainly derives from single centre experiences where PAES cases are centralised and treated periodically. This study evaluated clinical outcomes of surgical treatment for PAES in a clinical setting where PAES cases were not centralised. METHODS: Multicentre, retrospective cohort study using a national clinical registry. From a Japanese nationwide clinical registry, data for patients who underwent surgical treatment for PAES between 2013 and 2018, including 58 limbs from 41 institutes, were retrieved and evaluated. Patency was analysed using Kaplan-Meier curves. RESULTS: The mean patient age was 36 ± 19 years, 78% were male, and the incidence of PAES was 0.24 limbs/centre/year, reflecting a clinical setting where PAES cases are not centralised. The most frequent arterial symptom was intermittent claudication (90%). Computed tomography was performed in 57 limbs (98%) for the diagnosis, however active manoeuvres such as dorsiflexion and plantarflexion during the examination was performed in only 13 limbs (22%), and occlusion of the popliteal artery was present in 38 limbs (66%) at diagnosis. Regarding surgical treatment, myotomy alone was performed in only seven limbs (12%), and other limbs were revascularised. Mean follow up was 26 ± 20 months, and surgical treatment was effective as it relieved symptoms in > 96% of limbs, with five year primary and secondary patency of the surgical treatment for PAES of 72% and 93%, respectively. CONCLUSION: Results of surgical treatment were acceptable even in a clinical setting where PAES cases were not centralised. However, a low incidence of active manoeuvres performed during the examination and a high incidence of occlusion at diagnosis suggests there may be delayed or underdiagnosis of PAES in Japan, and increased awareness for PAES is warranted.

Recommendations for the management of the vascular involvement in Behçet's disease by the Japanese National Research Committee for Behçet's disease-secondary publication.

OBJECTIVES: This study aimed to develop clinical guidelines for the management of vascular Behçet's disease (BD) by the Behçet's Disease Research Committee of the Ministry of Health, Labour and Welfare of the Japanese Government. METHODS: A task force proposed clinical questions (CQs) concerning vascular BD based on a literature search. After screening, draft recommendations were developed for each CQ and brushed up in three blinded Delphi rounds, leading to the final recommendations. RESULTS: This study provides recommendations for 17 CQs concerning diagnosis and differential diagnoses, assessment of disease activity, and treatment. The guidelines recommend immunosuppressive treatments, for both arterial and venous involvement with active inflammation. Anticoagulation is also recommended for deep vein thrombosis except in high-risk patients. Surgical and endovascular therapies can be optional, particularly in patients with urgent arterial lesions undergoing immunosuppression. In addition, two sets of algorithms for diagnosis and treatment are shown for arterial and venous involvement. CONCLUSIONS: These recommendations are expected to serve as useful tools in the daily clinical practice of BD. This content has already been published in Japanese in the Guideline for the Management of Behçet's Disease 2020 and is submitted with permission from both the primary and secondary publishers.

Prediction Models for Two Year Overall Survival and Amputation Free Survival After Revascularisation for Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to create prediction models for two year overall survival (OS) and amputation free survival (AFS) after revascularisation in patients with chronic limb threatening ischaemia (CLTI). METHODS: This was a retrospective analysis of prospectively collected multicentre registry data (JAPAN Critical Limb Ischaemia Database; JCLIMB). Data from 3 505 unique patients with CLTI who had undergone revascularisation from 2013 to 2017 were extracted from the JCLIMB for the analysis. The cohort was randomly divided into development (2 861 patients) and validation cohorts (644 patients). In the development cohort, multivariable risk models were constructed to predict two year OS and AFS using Cox proportional hazard regression analysis. These models were applied to the validation cohort and their performances were evaluated using Harrell's C index and calibration plots. RESULTS: Kaplan-Meier estimates of two year OS and AFS post-revascularisation in the whole cohort were 69% and 62%, respectively. Strong predictors for OS consisted of age, activity, malignant neoplasm, chronic kidney disease (CKD), congestive heart failure (CHF), geriatric nutritional risk index (GNRI), and sex. Strong predictors for AFS included age, activity, malignant neoplasm, CKD, CHF, GNRI, body temperature, white blood cells, urgent revascularisation procedure, and sex. Prediction models for two year OS and AFS showed good discrimination with Harrell's C indexes of 0.73 (95% confidence interval [CI] 0.69 - 0.77) and 0.72 (95% CI 0.68 - 0.76), respectively CONCLUSION: Prediction models for two year OS and AFS post-revascularisation in patients with CLTI were created. They can assist in determining treatment strategies and serve as risk adjustment modalities for quality benchmarking for revascularisation in patients with CLTI at each facility.

Establishing clinical remission criteria and the framework of a treat-to-target algorithm for Takayasu arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour and Welfare for intractable vasculitis.

OBJECTIVES: To develop a proposal for remission criteria and a framework for a treat-to-target (T2T) algorithm for Takayasu arteritis (TAK). METHODS: A study group of the large-vessel vasculitis group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis consists of 10 rheumatologists, 5 cardiologists, 1 nephrologist, 1 vascular surgeon, 1 cardiac surgeon, and 2 paediatric rheumatologists. A Delphi survey of remission criteria items was circulated among the study group over four reiterations. To develop the T2T algorithm, the study group conducted four face-to-face meetings and two rounds of Delphi together with three patients. RESULTS: Initial literature review resulted in a list of 117 candidate items for remission criteria, of which 56 items with a mean score of ≥4 (0-5) were extracted including disease activity domains and treatment/comorbidity domains. The study group provided six overarching principles for the T2T algorithm, two recommendations on treatment goals, five on evaluation of disease activity and imaging findings including positron emission tomography-computed tomography, and two on treatment intensification. CONCLUSIONS: We developed a T2T algorithm and proposals for standardised remission criteria by means of a Delphi exercise. These will guide future evaluation of different TAK treatment regimens.

Effect of Treatment With Sodium-Glucose Cotransporter 2 Inhibitor on the Initiation of Continuous Positive Airway Pressure Therapy in Type 2 Diabetic Patients With Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obese patients with type 2 diabetes mellitus often develop obstructive sleep apnea syndrome (OSAS). In this study, continuous positive airway pressure (CPAP) was initiated in Japanese patients with type 2 diabetes mellitus who developed OSAS during treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the effect of the SGLT2 inhibitor therapy on the patients was investigated. METHODS: The study was conducted in outpatients with type 2 diabetes mellitus with serum hemoglobin A1c (HbA1c) values of ≥ 6.5% who developed OSAS. The patients were divided into two groups according to whether they were receiving treatment with an SGLT2 inhibitor or with other oral hypoglycemic agents: the SGLT2 inhibitor group (n = 9) and non-SGLT2 inhibitor group (n = 7). The patients in the former group were under treatment with one of the following three SGLT2 inhibitors: luseogliflozin (2.5 mg/day), dapagliflozin (5 mg/day) and empagliflozin (10 mg/day). The patients took the drugs once daily, before or after breakfast. The patients were initiated on CPAP therapy for OSAS, and their weight, body mass index (BMI), serum HbA1c level, lipid profile, liver function parameters, serum uric acid, and apnea-hypopnea index (AHI) measured before the initiation of CPAP therapy (baseline) were compared with the values measured 3 months after the start of CPAP therapy. RESULTS: The AHI decreased significantly after 3 months of CPAP therapy, as compared to that at the baseline, in both the SGLT2 inhibitor and non-SGLT2 inhibitor groups. There was no significant change in the serum HbA1c value after 3 months of CPAP therapy as compared to that at the baseline in either group. The body weight and BMI increased significantly after 3 months of CPAP therapy in the SGLT2 inhibitor group, but not in the non-SGLT2 inhibitor group. CONCLUSION: The body weight and BMI increased significantly after 3 months of CPAP therapy initiated for OSAS in the type 2 diabetic patients who were receiving SGLT2 inhibitor therapy. Thus, when CPAP therapy is adopted for an obese diabetic patient with OSAS, it should be borne in mind that the body weight may increase if the patient is receiving SGLT2 inhibitor treatment.

Influence of Luseogliflozin on Vaginal Bacterial and Fungal Populations in Japanese Patients With Type 2 Diabetes.

BACKGROUND: Selective sodium-glucose cotransporter 2 inhibitors, known to lower the blood glucose levels by promoting the urinary glucose excretion, can predispose to genitourinary infections. This prospective study investigated the influence of selective sodium-glucose cotransporter 2 inhibitors luseogliflozin on the vaginal flora of the pre- and postmenopausal women with type 2 diabetes mellitus. METHODS: Twelve premenopausal and 24 postmenopausal female Japanese patients with type 2 diabetes mellitus took luseogliflozin 2.5 mg once daily for 6 months. The intravaginal fungal and bacterial populations, together with the body weight and serum parameters of diabetes mellitus and lipid metabolism were measured before and after the treatment. RESULTS: After luseogliflozin treatment, the body weight, body mass index and hemoglobin A1c decreased, and the serum levels of high-density lipoprotein cholesterol increased significantly. Luseogliflozin treatment revealed to increase vaginal colony concentrations of Enterococcus faecalis (P = 0.0077) and E. coli (P = 0.0201) in premenopausal patients, and Enterococcus faecalis (P = 0.0051) and Candida albicans (P = 0.0355) in postmenopausal patients. In both pre- and postmenopausal patients, colony concentrations of Staphylococcus spp. had decreased (P = 0.0261 and P = 0.0161). CONCLUSIONS: Treatment with selective sodium-glucose cotransporter 2 inhibitors luseogliflozin was associated with changes of the vaginal flora. These findings provide basic data on the increased susceptibility to genital infections during luseogliflozin treatment.

The Effects of Pemafibrate in Japanese Patients with Type 2 Diabetes Receiving HMG-CoA Reductase Inhibitors.

OBJECTIVE: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemic agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, therefore, this combination required careful administration for patients. In the present study, the effects of combination therapy of pemafibrate, a novel fibrate, and statins, was evaluated. METHODS: Pemafibrate was administered for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group was examined. RESULTS: In the combination group, a decrease in serum total cholesterol levels was observed after 6 months of pemafibrate treatment compared to baseline, along with an increase in HDL-cholesterol. While serum triglyceride level was reduced, HbA1c level was elevated in both the groups. Serum creatinine kinase level, which is an indicator of myopathy, was lowered in the combination group. In addition, a decrease in γ-glutamyl transpeptidase, a parameter of hepatic dysfunction, was observed in the combination group. CONCLUSION: The statin-pemafibrate combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.

Current Trends in Epidemiology and Clinical Features of Thromboangiitis Obliterans in Japan　- A Nationwide Survey Using the Medical Support System Database.

BACKGROUND: The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79-8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45-5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00-7.31) in FY 2008 to 6.12% (95% Cl: 5.98-6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya's criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis. CONCLUSIONS: The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

Asia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee.

BACKGROUND: Peripheral artery disease (PAD) is the most underdiagnosed, underestimated and undertreated of the atherosclerotic vascular diseases despite its poor prognosis. There may be racial or contextual differences in the Asia-Pacific region as to epidemiology, availability of diagnostic and therapeutic modalities, and even patient treatment response. The Asian Pacific Society of Atherosclerosis and Vascular Diseases (APSAVD) thus coordinated the development of an Asia-Pacific Consensus Statement (APCS) on the Management of PAD. OBJECTIVES: The APSAVD aimed to accomplish the following: 1) determine the applicability of the 2016 AHA/ACC guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease to the Asia-Pacific region; 2) review Asia-Pacific literature; and 3) increase the awareness of PAD. METHODOLOGY: A Steering Committee was organized to oversee development of the APCS, appoint a Technical Working Group (TWG) and Consensus Panel (CP). The TWG appraised the relevance of the 2016 AHA/ACC PAD Guideline and proposed recommendations which were reviewed by the CP using a modified Delphi technique. RESULTS: A total of 91 recommendations were generated covering history and physical examination, diagnosis, and treatment of PAD-3 new recommendations, 31 adaptations and 57 adopted statements. This Asia-Pacific Consensus Statement on the Management of PAD constitutes the first for the Asia-Pacific Region. It is intended for use by health practitioners involved in preventing, diagnosing and treating patients with PAD and ultimately the patients and their families themselves.

Effects of Additional Administration of a Selective Inhibitor of Sodium Glucose co-transporter-2 Inhibitor on the Glycemic Control in Japanese Type 2 Diabetes Mellitus Patients Receiving Treatment with a Dipeptidyl Peptidase-4 Inhibitor.

We conducted this study to determine whether additional administration sodium-glucose co-transporter 2 (SGLT2) inhibitor might provide further improvement of glycemic control and also to explore any advantages in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment dipeptidyl peptidase-4 (DPP-4) inhibitors. We divided the patients in two groups, MT group and CT group. The MT group were continued on the DPP-4 inhibitor treatment for 6-months, and CT group were additionally administered an SGLT2 inhibitor treatment for 6-months. The MT group showed a significant decrease of hemoglobin A1c (HbA1c), but a significant increase of body weight, body mass index and serum uric acid, compared to the baseline values, while the CT group showed a significant decrease of HbA1c, body weight, BMI, and serum uric acid, and also a significant increase of serum HDL-cholesterol and decrease of serum triglyceride levels. Furthermore, this group showed a significant decrease of serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GTP), which are markers of liver function. These results suggest that the combination therapy is useful, in particular, for the treatment of type 2 diabetes mellitus patients with hyperlipidemia and liver dysfunction. Among the SGLT2 inhibitors added to the DPP-4 inhibitor treatment, the decreases of serum levels of AST, ALT and γ-GTP were particularly significant in the group receiving luseogliflozin, suggesting that the combination of a DPP-4 inhibitor with luseogliflozin is particularly effective for the treatment of type 2 diabetes mellitus patients with liver dysfunction.

Bicycle exercise training improves ambulation in patients with peripheral artery disease.

OBJECTIVE: Exercise training has multiple beneficial effects in patients with arteriosclerotic diseases; however, the exact underlying mechanisms of the effects are not completely understood. This study aimed to evaluate the effectiveness of a supervised exercise program in improving gait parameters, including the variability and walking performance of lower limb movements, in patients with peripheral artery disease (PAD) and intermittent claudication (IC). METHODS: Sixteen patients with a history of PAD and IC were recruited for this study, and they completed a 3-month supervised bicycle exercise program. The ankle-brachial index and responses to quality of life (QOL) questionnaires were evaluated. Near-infrared spectroscopy was also performed to determine the hemoglobin oxygen saturation in the calf. Patients' kinematics and dynamics, including joint range of motion and muscle tension, were evaluated using an optical motion capture system. Computed tomography images of each muscle were assessed by manual outlining. Data were collected before and after the supervised bicycle exercise program, and differences were analyzed. RESULTS: Significant differences were not found in step length, ankle-brachial index, and hemoglobin oxygen saturation before and after the supervised bicycle exercise program; however, IC distance (P = .034), maximum walking distance (P = .006), and all QOL questionnaire scores (P < .001) showed significant improvement. Hip range of motion (P = .035), maximum hip joint torque (right, P = .031; left, P = .044), maximum tension of the gluteus maximus muscle (right, P = .044; left, P = .042), and maximum hip joint work (right, P = .048; left, P = .043) also significantly decreased bilaterally. Computed tomography images showed a significant increase in the cross-sectional area of the abdominal, trunk, and thigh muscles but not in that of the lower leg muscles after the supervised exercise program intervention. CONCLUSIONS: In this study, bicycle exercise training improved the QOL and walking distance and decreased hip movement. The results showed that bicycling might be as useful as walking in patients with PAD.