Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism　- The Primary Results From the KUROSIO Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients. METHODS AND RESULTS: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively. CONCLUSIONS: The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.

Impact of Anemia on Clinical Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis Receiving Edoxaban　- Insights From the ONCO DVT Study.

BACKGROUND: The ONCO DVT study demonstrated potential benefits of extended edoxaban treatment in patients with isolated distal deep vein thrombosis in terms of thrombotic risk. However, the risk-benefit balance in patients with anemia remains unclear. METHODS AND RESULTS: This prespecified subgroup analysis included 601 patients, divided into anemia (n=402) and no-anemia (n=199) groups. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death. Anemia was defined as hemoglobin <12 g/dL for women and <13 g/dL for men. In the anemia subgroup, the primary endpoint occurred in 3 (1.5%) and 17 (8.4%) patients in the 12- and 3-month edoxaban treatment groups, respectively (odds ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.58), compared with 0 and 5 (4.9%) patients, respectively, in the no-anemia subgroup (P interaction=0.997). Major bleeding occurred in 26 (13.1%) and 17 (8.4%) patients with anemia in the 12- and 3-month edoxaban treatment groups, respectively (OR 1.64; 95% CI 0.86-3.14), compared with 2 (2.1%) and 5 (4.9%) patients without anemia (OR 0.67; 95% CI 0.26-1.73; P interaction=0.13). CONCLUSIONS: Regardless of the presence of anemia, edoxaban treatment for 12 months was superior to treatment for 3 months in reducing thrombotic events, whereas the risk of major bleeding did not differ significantly between the 2 treatment groups.

Revascularization and Digestive Tract Repair in Secondary Aortoenteric Fistula Using a Single-Center in Situ Revascularization Strategy.

BACKGROUND: Information regarding optimal revascularization and digestive tract repair in secondary aortoenteric fistula (sAEF) remains unclear. Thus, reporting treatment outcomes and presenting comprehensive patient details through a structured treatment approach are necessary to establish a treatment strategy for this rare, complex, and fatal condition. METHODS: We performed a single-center retrospective review of consecutive sAEF managed based on our in situ revascularization and intestinal repair strategy. The primary endpoint of this study was all-cause mortality, and secondary endpoints were the incidence of in-hospital complications and midterm reinfections. RESULTS: Between 2007 and 2020, 16 patients with sAEF, including 13 men (81%), underwent in situ revascularization and digestive tract repair. The median follow-up duration for all participants was 36 (interquartile range, 6-62) months. Among the participants, 81% (n = 13), 13% (n = 2), and 6% (n = 1) underwent aortic reconstruction with rifampin-soaked grafts, unsoaked Dacron grafts, and femoral veins, respectively. The duodenum was the most commonly involved site in enteric pathology (88%; n = 14), and 57% (n = 8) of duodenal breaks were repaired by a simple closure. Duodenum's second part-jejunum anastomosis was performed in 43% of patients (n = 6), and 19% of the patients (n = 3) died perioperatively. In-hospital complications occurred in 88% patients (n = 14), and the most frequent complication was gastrointestinal. Finally, 81% patients (n = 13) were discharged home. Oral antibiotics were administered for a median duration of 5.7 months postoperatively; subsequently, the participants were followed up carefully. Reinfection was detected in 6% of the patients (n = 1) who underwent reoperation without any complications. The 1-year and 3-year overall survival rates of participants were 75% (n = 12) and 75% (n = 9), respectively, and no sAEF-related deaths occurred, except perioperative death. CONCLUSIONS: Surgical intervention with contemporary management based on our vascular strategy and digestive tract procedure may be a durable treatment for sAEF.

Type 2 Endoleak Detection After Endovascular Aneurysm Repair: Can Low-Flow Endoleaks Also Be Visualized in Silicon-Photomultiplier-Based Positron Emission Tomography/Computed Tomography Scans?

PURPOSE: To present a novel clinical application of silicon-photomultiplier-based positron emission tomography (SiPM-based PET)/computed tomography (CT), detecting a type II endoleak 5 years after endovascular aneurysm repair (EVAR). TECHNIQUE: SiPM-based PET/CT scans with a standard whole-body protocol were performed for a 73-year-old man with a past medical history of abdominal aortic aneurysms treated with EVAR and currently under investigation of his duodenal papillary carcinoma. The PET/CT demonstrated 18F-fluorodeoxyglucose (FDG) accumulation outside the stent graft in the native sac of the aneurysm. The site of accumulation corresponded to that of the contrast enhancement depicted in the CT angiography taken 1 month earlier. Another CT scan performed 3 months later revealed enlargement of the aneurysm. CONCLUSION: SiPM-based PET/CT, with its superior sensitivity and spatial resolution over conventional PET/CT, can detect type II low-flow endoleaks. CLINICAL IMPACT: Abnormal intra-aneurysmal FDG activity incidentally detected on SiPM-based PET/CT is worthy of attention because it may be indicative of endoleaks. Additional imaging using different modalities should be considered so that the patient would not miss the additional treatment opportunity upon observing sac enlargement. For patients with contraindications for iodine CT contrast media, SiPM-based PET/CT would serve as a suitable alternative.

Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission　- From the CLOT-COVID Study.

BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 µg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 µg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

Mortality-associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.

BACKGROUND: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSION: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

Presence of Helicobacter cinaedi in Atherosclerotic Abdominal Aortic Aneurysmal Wall.

Recently, the relationship between Helicobacter cinaedi (H. cinaedi) infection and several diseases, including cardiovascular and central nervous system disorders, bone and soft tissue disorders, and infectious abdominal aortic aneurysms (AAAs), has been reported. Moreover, H. cinaedi may be associated with arteriosclerosis. In the present study, we investigated the association between H. cinaedi infection and clinically uninfected AAAs. Genetic detection of H. cinaedi in the abdominal aneurysm wall was attempted in 39 patients with AAA undergoing elective open surgery between June 2019 and June 2020. DNA samples extracted from the arterial wall obtained during surgery were analyzed using nested polymerase chain reaction (PCR). The target gene region was the H. cinaedi-specific cytolethal distending toxin subunit B (cdtB). Nine (23.1%) of 39 patients showed positive bands corresponding to H. cinaedi, and further sequencing analyses demonstrated the presence of H. cinaedi DNAs in their aneurysm walls. In contrast, all the non-aneurysm arterial walls in our patients were negative for H. cinaedi. In conclusion, this is the first report of the detection of H. cinaedi in the walls of a clinically non-infectious AAA.

Therapeutic-Dose vs. Prophylactic-Dose Anticoagulation Therapy for Critically Ill Patients With COVID-19 in a Practice-Based Observational Study.

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

Successful Treatment of Giant Common and Proper Hepatic Artery Aneurysm Complicating Autosomal Dominant Polycystic Kidney Disease.

Hepatic artery aneurysms (HAAs) complicating autosomal dominant polycystic kidney disease (ADPKD) are extremely rare. On account of the large number of renal cysts in ADPKD, ingenuity is required to safely perform surgery for HAA. Here, we present the case of a 60-year-old man with a common and proper HAA of >60 mm complicated with ADPKD. In this patient, difficulty in maintaining the field of view was expected during surgery. Hence, we performed a hybrid approach with celiac-to-right hepatic artery bypass by puncturing the femoral artery and cannulating the splenic artery to allow celiac-splenic artery balloon occlusion in case of rupture. More than 5 years postoperatively, the graft is patent without intervention.

Prospective clinical study for claudication after endovascular aneurysm repair involving hypogastric artery embolization.

PURPOSE: This prospective study aimed to assess the prognosis of claudication after endovascular aneurysm repair (EVAR) involving hypogastric artery (HGA) embolization. METHODS: Patients who were scheduled to undergo EVAR involving bilateral or unilateral HGA embolization (BHE or UHE, respectively) between May 2017 and January 2019 were included in this study. Patients underwent the walk test preoperatively, one week postoperatively, and monthly thereafter for six months. The presence of claudication and the maximum walking distance (MWD) were recorded. A near-infrared spectroscopy monitor was placed on the buttocks, and the recovery time (RT) was determined. A walking impairment questionnaire (WIQ) was completed to determine subjective symptoms. RESULTS: Of the 13 patients who completed the protocol, 12 experienced claudication in the 6-min walk test. The MWD was significantly lower at one week postoperatively than preoperatively. The claudication prevalence was significantly higher at five and six months postoperatively after BHE than after UHE. BHE was associated with longer RTs and lower WIQ scores than UHE. CONCLUSIONS: We noted a trend in adverse effects on the gluteal circulation and subjective symptoms ameliorating within six months postoperatively, with more effects being associated with BHE than with UHE. These findings should be used to make decisions concerning management strategies for HGA reconstruction.

Comparison of Edoxaban and Warfarin for the Treatment of Cancer-Associated Venous Thromboembolism　- A Retrospective Observational Study.

BACKGROUND: Because anticoagulant drugs for ambulatory patients with cancer-associated venous thromboembolism (CAT) are limited to warfarin and direct oral anticoagulants (DOACs) in Japan, it is important to assess the outcomes of both drugs.Methods and Results:We retrospectively assessed the outcomes of CAT patients who were treated with warfarin or edoxaban between 2011 and 2017. The assessment was limited to the duration of anticoagulant administration. CAT patients who did not receive anticoagulation therapy were also compared with the warfarin and edoxaban groups. We enrolled 111 CAT patients treated with warfarin (n=58, mean age 62.6 years, mean time in therapeutic range [TTR] % 61.1) or edoxaban (n=53, mean age 64.6 years). Although venous thromboembolism (VTE) recurred in 2 warfarin-treated patients, the 2 treatment groups were not significantly different (P=0.18). Bleeding during anticoagulation therapy occurred in 6 warfarin-treated patients (2 with major bleeding) and in 5 edoxaban-treated patients (no major bleeding) (P=1.0). The non-anticoagulation group (n=37) showed a high recurrence rate (P<0.01) compared with the anticoagulant group. CONCLUSIONS: This study showed that warfarin and edoxaban are equally effective in preventing VTE recurrence and bleeding. However, warfarin control in CAT patients presented some difficulties. This study also demonstrated the efficacy of anticoagulant drugs, compared with no anticoagulation, for CAT patients to prevent VTE recurrence.

Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE. CONCLUSIONS: Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.

Detection of Macrophage Localization in the Abdominal Aortic Aneurysm Wall Using Ex Vivo Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Macrophages in the aneurysmal wall play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Superparamagnetic iron oxide (SPIO) is a macrophage-specific contrast agent that results in negative enhancement on magnetic resonance imaging (MRI). SPIO-enhanced MRI targeting the intraluminal thrombus of AAAs has been previously reported. However, macrophages in the media and adventitia of AAA wall have not been investigated in detail. This study aimed to evaluate macrophage localization using SPIO-enhanced MRI in the media and adventitia of AAA wall, as macrophages play a crucial role in AAA pathogenesis. METHODS: Here, we included study and control patients planning to undergo open surgery for AAA. The study patients received SPIO injection 2 days preoperatively (the SPIO group, n = 7), whereas the control patients did not receive this injection (the control group). Ex vivo MRI was performed on the harvested AAA wall in the SPIO group during the surgery. The concordance between the number of macrophages and berlin blue (BB)-stained areas was histologically evaluated in both groups. Moreover, the concordance between regions of interest in MR images and BB-stained areas was evaluated. RESULTS: The proportion of BB-stained macrophages was higher in the SPIO group (0.93; interquartile range [IQR], 0.83-0.95) than in the control group (0.03; IQR, 0.026-0.11) (P < 0.05), indicating uptake of SPIO by macrophages in the AAA wall. A significant positive correlation was found between the number of BB-stained macrophages and BB-stained areas using Kendall rank correlation coefficient in the SPIO group (τ = 0.58; P < 0.05). Significant correlations were found in the distributions of the region of interest of SPIO-enhanced MRI and BB-stained areas in the media and adventitia in 5 of 7 patients. CONCLUSIONS: Macrophages present in the media and adventitia of the AAA wall showed an uptake of the SPIO contrast agent injected 2 days prior, which were then detected by ex vivo MRI. This suggests that SPIO-enhanced MR images help detect the localization of macrophages on the AAA wall, indicating its potential to serve as a novel index for AAA pathogenesis.

Midaortic Syndrome due to Takayasu Arteritis in a Child with Acute Decompensated Cardiac Failure Managed by an Emergency Axillo-External Iliac Artery Bypass: A Follow-Up Case Report of Long-Term Outcomes.

Midaortic syndrome (MAS) is characterized by a diffuse narrowing of the distal thoracic or abdominal aorta and is concomitant with various etiologies. The common symptoms of MAS include severe hypertension or arterial insufficiency distal to the stenosis. This includes lower extremity claudication and heart failure due to afterload mismatch. We present the case of an 8-year-old girl who developed acute decompensated cardiac, respiratory, and renal failures because of the occlusion of the descending aorta secondary to Takayasu arteritis (TA). Although thoracoabdominal-aortic bypass is usually performed for patients with MAS, the procedure was considered too invasive, given the patient's condition. Therefore, we performed an emergency axillo-external iliac artery bypass for revascularization. Subsequently, organ failure improved and she was discharged. At postoperative 10 years, an asymptomatic pseudoaneurysm was detected at the distal anastomosis, for which revision surgery was performed. Overall, the long-term prognosis was satisfactory, suggesting that this procedure is less invasive and effective for treatment of MAS due to TA, in emergencies.

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　- Positive Association.

BACKGROUND: The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.Methods and Results:This retrospective cohort study included 176 patients who attended Tohoku University Hospital with infrarenal fusiform AAA. AAA expansion rate was determined on multidetector computed tomography, and the correlations between expansion rate and the clinical data were analyzed. The median expansion rate was 2.405 mm/year. On univariate analysis, a significant positive correlation with expansion rate was observed for the initial MAD (P<0.001) and significant negative correlations for oral angiotensin receptor blocker usage (P=0.025), height (P=0.005), body weight (P=0.017), total cholesterol (P=0.007), low-density lipoprotein cholesterol (P=0.004), and HbA1c (P=0.037). On logistic regression analysis, significant positive associations with expansion rate were observed for initial MAD (P<0.001) and oral steroid usage (P=0.029) and a negative association for height (P=0.041). CONCLUSIONS: Oral steroid usage is an important risk factor for AAA expansion, independent of other risk factors of atherosclerosis and MAD.

Histological Analysis of a New Route after Subintimal Crural Angioplasty.

BACKGROUND: Subintimal angioplasty is an alternative approach in treating critical limb ischemia with crural artery disease. However, route or location of the newly created channel is not understood. CASE PRESENTATION: A 68-year-old man was referred to our hospital with ischemic gangrene of the right big toe. We performed endovascular treatment because he was a poor candidate for bypass surgery. The posterior tibial artery was treated using subintimal angioplasty, although it resulted in early occlusion. We decided that he was not able to receive any further limb salvage treatment and performed amputation below the knee 7 days after treatment. The specimen from the origin of posterior tibial artery to plantar artery bifurcation was resected and the formalin-fixed vessel was cut into 39 segments. Histological analysis showed that the newly formed lumen was comparatively well dilated and created in the media by tearing internal elastic lamina in almost the whole of its length. The severely poor runoff vessels below the ankle were thought to be a main cause of early occlusion. CONCLUSIONS: The newly formed lumen by subintimal crural angioplasty could be well dilated and created in the media.

Serious Adverse Events with Cyanoacrylate Closure of Varicose Veins: An Initial Report from a Large-Scale National Survey in Japan.

Objective: Cyanoacrylate closure (CAC) is a minimally invasive technique for the treatment of varicose veins. A recent paper reported serious adverse events (AEs) associated with this use. This triggered an urgent survey to determine the incidence of AEs in Japan. Methods: The CAC-AE survey was sent to all 1,030 institutions authorized for CAC treatments. Cases performed between January 2020 and October 2023 were surveyed. Data on serious AEs and mortality were collected. Results: There were 623 surveys returned. There were 16 cases of proximal deep vein thrombosis, 3 cases of pulmonary embolism (PE), and 0 cases of stroke. Deep vein occlusion due to cyanoacrylate extension was observed in 1 case. Vein resection due to infection was observed in 4 cases. There were 299 cases of localized phlebitis and/or allergic reactions requiring steroid administration. Systemic allergic reactions requiring steroid administration were observed in 66 cases. There was no anaphylaxis associated with cyanoacrylate. There was one postoperative death from PE. Conclusion: This report's intent is to provide real world data on serious AEs following CAC from Japan given current concern over these events. An extensive report investigation of individual complications with analysis including causality will be provided following a full investigation separately.

Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study.

BACKGROUND: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk. METHODS AND RESULTS: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07). CONCLUSIONS: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy. TRIAL REGISTRATION NUMBER: NCT03895502 (ONCO DVT Trial): https://classic.clinicaltrials.gov/ct2/show/NCT03895502.