Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

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.

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.

Concomitant carotid endarterectomy and aortic valve replacement in a patient with high risk of perioperative stroke.

Surgical strategy for significant carotid artery stenosis complicated with severe aortic valve stenosis is still controversial. Herein, we report a case of 80-year-old female in whom 78% stenosis by the NASCET criteria in left internal carotid artery was pointed out during preoperative checkup for symptomatic severe aortic stenosis. Carotid endarterectomy was done concomitantly with aortic valve replacement. No neurological complication occurred perioperatively.

Prospective Registry of Rivaroxaban Management of Cancer-Associated Venous Throboembolism (PRIMECAST) Study.

Background: The incidence of thromboembolism in patients with cancer is approximately 11%, and the risk of thrombosis in patients with malignant tumors is 6-fold higher than that in healthy persons. Thrombosis not only disrupts the treatment of cancer but also induces deterioration of quality of life (QOL). Knowledge about thrombus treatment is limited, and evidence is scarce. Clarification of the status and safety of venous thromboembolism (VTE) treatment in patients with cancer will contribute to active intervention and improvement of prognosis and QOL. In this study, the therapeutic effects of a non-vitamin K antagonist oral anticoagulant for VTE and the prognosis of cancer after treatment will be examined to establish a therapeutic method for VTE in patients with cancer. Methods and Results: A multicenter, non-interventional, observational study will be conducted in patients with cancer who developed VTE and underwent anticoagulant therapy with rivaroxaban (group A) or warfarin (group B) for 24 weeks. The primary endpoint will be the recurrence/aggravation of symptomatic VTE or occurrence/aggravation of deep vein thrombosis. Registration of 500 patients is needed in order to calculate the 95% confidence interval of the event rate at ±1% precision. Conclusions: The investigation period will run from January 2019 to December 2023 with ongoing selection of patients. Trial registration: no. 5-18-32 (approved 1 August 2018).

Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries.

In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis.

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium.

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.

Favorable outcomes of very elderly patients with critical limb ischemia who undergo distal bypass surgery.

OBJECTIVE: To determine the midterm outcomes of distal bypass surgery for very elderly patients, and to determine the ideal candidates for this procedure. METHODS: Of 268 consecutive patients (328 limbs) with critical limb ischemia who were treated between 2006 and 2013, 106 (126 limbs) underwent distal bypass and were retrospectively reviewed. Nineteen patients (22 limbs) were aged ≥80 years (very elderly group) and 87 patients (104 limbs) were aged <80 years (control group). RESULTS: The baseline characteristics differed between the 2 groups in terms of regular hemodialysis rate (very elderly group, 4 [21%] vs control group, 60 [69%]; P = .0002) and the Charlson comorbidity index (very elderly group, 3.2 ± 1.7 vs control group, 5.0 ± 2.0; P = .0005). According to the Rutherford category of limb ischemia (4/5/6), the very elderly and control groups were classified as 5/17/0 and 11/87/6, respectively (P = .18). Before the surgery, 17 patients (77%) and 67 patients (64%) were ambulatory in the very elderly and control groups, respectively. At follow-up at 29 ± 22 months, the rates of primary (P = .33) and secondary patency (P = .14), limb salvage (P = .50), survival (P = .26), amputation-free survival (P = .42), major adverse limb event and also perioperative death (P = .11), and major adverse cardiovascular events (P = .36) did not significantly differ between the groups. In multivariate analysis, a history of coronary artery disease (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.9; P = .005), preoperative nonambulatory status (HR, 4.2; 95% CI, 2.1-8.1; P < .0001), and serum albumin levels <3 g/dL (HR, 2.7; 95% CI, 1.3-5.4; P = .01) were significantly related to poor amputation-free survival. Thirteen patients (59%) remained ambulatory at the latest follow-up. In 91 patients (110 limbs) with tissue loss, the Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on Wound, Ischemia, and foot Infection classification stages 3 and 4 negatively affected complete wound healing, according to multivariate analysis (HR, 0.34; 95% CI, 0.20-0.61; P = .0005). CONCLUSIONS: A very elderly age should not preclude a patient from undergoing distal bypass surgery. A history of coronary artery disease, a nonambulatory status, and hypoalbuminemia, along with the Wound, Ischemia, and foot Infection classification for patients with tissue loss, should be carefully considered to obtain the most benefit from distal bypass surgery.

Paramalleolar Arterial Bollinger Score in the Era of Diabetes and End-Stage Renal Disease - Usefulness for Predicting Operative Outcome of Critical Limb Ischemia.

BACKGROUND: The aim of this study was to evaluate the usefulness of paramalleolar arterial Bollinger score (PBS) for predicting postoperative outcome of infra-popliteal bypass surgery for critical limb ischemia (CLI). METHODS AND RESULTS: A total of 104 consecutive patients (118 limbs) who underwent infra-popliteal (tibial or paramalleolar) arterial bypass surgery with an autologous vein conduit for the treatment of CLI (Rutherford 4-6) between January 2002 and December 2012 were classified according to PBS ≤45 or >45. Postoperative outcome was compared between these groups. Primary outcomes were major adverse limb events plus perioperative death, and amputation-free survival (AFS). The secondary outcomes were overall survival, limb salvage and secondary graft patency. More than 80% of patients had either diabetes mellitus (DM) or end-stage renal disease (ESRD) and 30 patients with 36 limbs had PBS >45. Compared with the PBS ≤45 group, the PBS >45 group had higher CVD and carotid stenosis rate, poor nutrition status and lower malignancy rate. On overall analysis, the PBS >45 group had worse outcome for AFS and survival but this was not statistically significant (P=0.12, NS). In DM or ESRD patients, the PBS >45 group had significantly worse outcome for both AFS (P=0.04, 0.02) and overall survival rate (P=0.04, 0.03). CONCLUSIONS: PBS successfully classified CLI patients with DM or ESRD who had worse outcome after infra-popliteal bypass surgery.

Practice Guidelines for Primary Care of Acute Abdomen 2015.

Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine, in collaboration with four other medical societies, launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines (all clinical questions and recommendations were shown in supplementary information). A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. A total of 108 questions based on nine subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

The Practice Guidelines for Primary Care of Acute Abdomen 2015.

BACKGROUND: Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine in collaboration with four other medical societies launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines [all clinical questions (CQs) and recommendations are shown in supplementary information]. METHODS: A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. RESULTS: A total of 108 questions based on 9 subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. CONCLUSIONS: The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

A perioperative strategy for abdominal aortic aneurysm in patients with chronic renal insufficiency.

PURPOSE: The outcomes of open surgical repair (OR) or endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) are favorable; however, pre-existing chronic renal insufficiency (CRI) is considered to be a risk factor that can affect the long-term outcome. We evaluated our surgical strategy for AAA in patients with CRI by analyzing their pre- and postoperative renal function. METHODS: We conducted a retrospective chart review of CRI patients who underwent OR (n = 28) or EVAR (n = 31) for infra-renal AAA in our institution between 2009 and 2013. Our operative strategy included pre- and postoperative adequate hydration, postoperative diuretics and low-dose dopamine for both groups, intravascular ultrasonography and carbon dioxide angiography to reduce the amount of contrast media needed in the EVAR group, and occasional intraoperative mannitol for the OR group. RESULTS: The preoperative estimated glomerular filtration rate (eGFR) increased significantly in the postoperative period and remained similar 6 months later in both groups, without any difference in changes between the groups. In-hospital postoperative complications included leg occlusion in one EVAR patient. There were no complication-related deaths in either group. CONCLUSIONS: Postoperative renal function was similar after the two approaches, indicating that both procedures could be performed safely using our strategy for patients with CRI.

Inverse Correlation Between Calcium Accumulation and the Expansion Rate of Abdominal Aortic Aneurysms.

BACKGROUND: When the maximal diameter of an abdominal aortic aneurysm (AAA) exceeds a threshold, the likelihood of catastrophic rupture increases markedly. Therefore, surveillance at optimal intervals should be offered to patients with AAA. However, other than AAA diameter, there is no useful marker or index for predicting the expansion rate of an AAA or determining the optimal intervals for surveillance. The aim of this study was to evaluate the usefulness of calcium accumulation in the AAA for predicting its expansion rate. METHODS AND RESULTS: We performed a retrospective cohort study in 414 patients with infrarenal AAA who visited The University of Tokyo Hospital. The maximal diameter and extent of calcification of each AAA were evaluated by multidetector-row computed tomography imaging. There was an inverse correlation between the extent of calcification and the subsequent AAA expansion. A lower extent of calcification in the AAA as well as the AAA diameter and absence of coronary artery disease correlated with an accelerated expansion of the AAA. CONCLUSIONS: In AAA, a lower extent of calcification correlated with accelerated expansion. The calcification index of an AAA can be a useful predictor of its expansion rate. The study findings also support the theory that the mechanisms for progression in atherosclerosis with calcification and external expansion of an aneurysm are distinct.

Useful predictors for critical limb ischemia in severely ischemic limbs.

BACKGROUND: The aim of this paper was to determine useful predictors for critical limb ischemia (CLI) occurrence in severely ischemic limbs. The contralateral limbs of patients with unilateral CLI were evaluated, with special respect to pulse volume recording (PVR). METHODS: Retrospective analysis of 102 consecutive patients (110 limbs) with unilateral CLI. We excluded patients with bilateral CLI, or without PVR data. PVR data were automatically quantitatively expressed as upstroke time (UT) and percentage mean artery pressure (%MAP). The role of PVR parameters was examined in relation to arterial occlusive disease in the lower limbs. Baseline characteristics and non-invasive laboratory data (including Ankle Brachial Index [ABI] and PVR data) were analyzed as predictors for CLI. RESULTS: After exclusion, 73 contralateral limbs of unilateral CLI patients (mean age, 70±12 years; 51 male, 70%) were investigated. Fifty patients (68%) had diabetes, and 41 patients (56%) were receiving hemodialysis. UT was longer in patients with crural arterial occlusive disease (214±55 versus 183±57 ms, P=0.02), although ABI was not different (P=0.31). In the follow-up of 19±12 months, 25 limbs progressed to CLI, and the cumulative incidence was 28% and 51% at 1 and 3 years, respectively. Multivariate analysis confirmed that abnormal %MAP (hazard ratio 5.9; 95% confidence interval, 1.8-27.0; P<0.01), coronary artery disease (CAD), and hypoalbuminemia were significant risk factors. CONCLUSIONS: %MAP, CAD, and hypoalbuminemia predicted CLI occurrence in the contralateral limbs of unilateral CLI patients.

Distal bypass to a critically ischemic foot increases the skin perfusion pressure at the opposite site of the distal anastomosis.

INTRODUCTION: The purpose of the study was to reveal the effect of blood flow supply to the foot by analyzing the skin perfusion pressure values and the pedal arch connection after bypass surgery. PATIENTS AND METHODS: We selected 48 operated limbs whose skin perfusion pressure was measured pre- and post-operatively on the opposite site of distal anastomosis. We also assigned the ischemic limbs to three groups according to the patency of the pedal arch: good, intermediate, and poor. RESULTS: The mean value of skin perfusion pressure increased significantly from 27.0 ± 14.9 to 52.8 ± 16.0 (p < 0.001) post-operatively. Skin perfusion pressure improved in most of the limbs post-operatively and decreased or unchanged in only four limbs, all of which showed improved tissue loss. Three amputated limbs were due to infection, and all showed an increase in skin perfusion pressure. CONCLUSION: It was difficult to correlate limb prognosis to skin perfusion pressure and the pedal arch connection.