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We developed five microsatellite primer pairs for the yellowtail Seriola quinqueradiata. The loci were highly polymorphic, with eight to 14 alleles per locus, and can be used to study kinship and/or population structure. Many of these primer pairs amplified polymorphic loci in cross-species amplification tests for two other Seriola species ( S. lalandi and S. dumerili). [ABSTRACT FROM AUTHOR]

Competing Interests: Funding Support and Author Disclosures Drs Kubo and Maruo are clinical proctors for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Research on the impact of angiographically detected residual trabeculation after left atrial appendage closure (LAAC) is limited., Objectives: To investigate the incidence, characteristics, and clinical implications of angiographically detected residual trabeculation after LAAC using the WATCHMAN device., Methods: We analyzed 1350 consecutive patients with atrial fibrillation undergoing LAAC using the WATCHMAN device from the OCEAN-LAAC registry, which is a prospective ongoing, multicenter Japanese registry. The inclusion criteria comprised patients who successfully underwent LAAC and whose presence or absence of residual trabeculation can be confirmed using a contrast medium. The clinical outcomes were compared between patients with and without angiographically detected residual trabeculation., Results: Residual trabeculation was angiographically detected in 5.6% (75/1350 patients). At the procedure, the proportion of peri-device leak (PDL) was significantly higher in the residual trabeculation group than in the non-residual trabeculation group (20% vs. 5.1%, p < 0.001). However, the PDL and device-related thrombosis at 45 days and 1 year were comparable between the two groups (37% vs. 23%, p = 0.24; 28% vs. 31%, p = 0.84; 2.1% vs. 1.4%, p = 0.50; 6.9% vs. 6.0%, p = 0.69, respectively). The 3-year cumulative incidence of ischemic stroke, all cardiovascular death, and all-cause death were comparable between the two groups (5.7% vs. 5.5%, log-rank p = 0.96; 7.7% vs. 8.9%, log-rank p = 0.34, 31.4% vs. 22.3%, log-rank p = 0.71, respectively)., Conclusion: The angiographically detected residual trabeculation rate was 5.6%, and this population had a significantly higher prevalence of PDL at the procedure. However, the presence of residual trabeculation did not contribute to PDL or device-related thrombosis at follow-up or affect the clinical outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Patients with atrial fibrillation and malignant left atrial appendage (LAA) may benefit from LAA closure (LAAC); however, evidence is limited., Objective: The purpose of this study was to determine management strategies and clinical outcomes in patients with atrial fibrillation and malignant LAA., Methods: Malignant LAA was defined as a history of ischemic stroke and/or evidence of LAA thrombus despite continuous oral anticoagulation (OAC) therapy (continuous for ≥3 weeks). We studied 80 patients with malignant LAA treated with LAAC. We compared these patients first against 44 patients with malignant LAA treated with OAC alone and second against 114 patients without malignant LAA who were treated with LAAC for conventional indications., Results: Among patients with malignant LAA (first comparison), those treated with LAAC had a higher 1-year cumulative incidence rate of ischemic stroke than did patients treated with OAC alone (6.3% vs 5.3%; log-rank, P = .09) whereas the difference in stroke risk while receiving OAC was comparable (2.7% vs 5.3%; log-rank, P = .84). Furthermore, all disabling stroke events in patients with malignant LAA treated with LAAC occurred only while not receiving OAC. Among patients treated with LAAC (second comparison), those with malignant LAA had a higher 1-year cumulative incidence rate of ischemic stroke (and ischemic stroke due to device-related thrombosis) than did those without malignant LAA (6.3% vs 2.2%; log-rank, P = .009 and 2.2% vs 0%; log-rank, P = .04, respectively). However, these differences in stroke risk were no longer significant while receiving OAC (2.7% vs 1.0%; log-rank, P = .11)., Conclusion: Combination performing LAAC and continuation of OAC may be options to prevent ischemic stroke in patients with high thromboembolic risk and malignant LAA., Competing Interests: Disclosures Drs Chatani and Kubo are clinical proctors for Boston Scientific and have received honoraria from Boston Scientific. All other authors declare no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Chronic total occlusion (CTO) lesions of the femoropopliteal artery have been shown to benefit from drug-coated balloon (DCB) angioplasty. However, because bailout stenting is often performed, the outcome of DCB angioplasty alone remains unknown, particularly the differences in outcomes between low-dose DCB (LD-DCB) and high-dose DCB (HD-DCB). To address these issues, we conducted a single-center, retrospective cohort study and enrolled 66 consecutive patients undergoing initial endovascular therapy with DCBs for femoropopliteal CTO lesions from June 2018 to February 2023. Of the 66 patients, 25 underwent LD-DCB angioplasty and 41 underwent HD-DCB angioplasty. In all lesions, no bailout stenting was performed and intraplaque wiring was confirmed by intravascular ultrasound. The primary outcome measure was 1-year primary patency and the secondary outcome measures were 1-year freedom from clinically driven target lesion revascularization (CD-TLR) and reocclusion. There were no significant differences between LD-DCB and HD-DCB angioplasty in patient and lesion characteristics, 1-year primary patency (76.4% vs. 85.9%, log-rank p = 0.51), CD-TLR (95.2% vs. 94.3%, log-rank p = 0.97), and reocclusion (95.0% vs. 94.3%, log-rank p = 0.99). Patients with two of the three risk factors for restenosis, i.e., minimum lumen area < 12.6 mm 2 , dissection angle > 63°, and calcification angle > 270°, had a significantly lower patency rate (no factor: 100% vs. 1 factor: 90.3% vs. 2 factors: 62.6%; log-rank p = 0.04). In patients undergoing DCB angioplasty for femoropopliteal CTO lesions, 1-year primary patency and freedom from CD-TLR were favorable, with no significant difference between LD-DCB and HD-DCB angioplasty., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC) with preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy. We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into three groups based on preprocedural thromboembolic or bleeding events under OAC therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3 year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32-15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45-58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with the conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC., Competing Interests: Declarations Conflict of interest The authors declare that there are no conflicts of interest., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: A small mitral valve area (MVA) is one of the challenging anatomies for transcatheter edge-to-edge repair (TEER) for mitral regurgitation, but the relationship between baseline MVA and clinical outcomes remains unknown. This study aimed to evaluate the association of baseline MVA with procedural and clinical outcomes in patients undergoing TEER with MitraClip from the OCEAN-Mitral registry (Optimized Catheter Valvular Intervention-Mitral)., Methods: A total of 1768 patients undergoing TEER were divided into 3 groups according to baseline MVA: group 1: <4.0 cm 2 , n=358; group 2: 4.0-5.0 cm 2 , n=493; and group 3: ≥5.0 cm 2 , n=917. The primary end point was a composite of all-cause death and heart failure hospitalization within 2 years of TEER and compared between the 3 groups., Results: Patients with smaller MVA had significantly fewer clips implanted and higher postprocedural transmitral mean pressure gradient. There was no significant difference in the acute procedural success rate and postprocedural mitral regurgitation severity between the 3 groups. The incidence of the primary end point was similar in group 1 compared with groups 2 and 3 (35.2% versus 34.5% versus 34.0%; P =0.96) and was also similar in patients with MVA <3.5 cm 2 and those with MVA 3.5 to 4.0 cm 2 . The adjusted risk of MVA <4.0 cm 2 relative to MVA of 4.0 to 5.0 cm 2 and MVA ≥5 cm 2 for the primary end point remained insignificant (hazard ratio, 1.06 [95% CI, 0.79-1.41]; P =0.68; hazard ratio, 0.99 [95% CI, 0.75-1.31]; P =0.96, respectively). At 1 year, no significant difference in the proportion of residual mitral regurgitation 3+/4+ was observed between the 3 groups (7.2% versus 4.4% versus 6.5%; P =0.49)., Conclusions: In patients undergoing TEER, a small MVA <4.0 cm 2 may limit the number of clips implanted and increase the transmitral pressure gradient after TEER, but baseline MVA was not associated with mitral regurgitation reduction and clinical outcomes., Registration: URL: https://center6.umin.ac.jp/cgiope n-bin/ctr/ctr&#95;view.cgi?recptno=R000027188; Unique identifier: UMIN000023653., Competing Interests: Drs Kubo, Maruo, Saji, Izumo, Watanabe, Amaki, Izumi, Enta, Shirai, Mizuno, Bota, Mizutani, Ueno, Yamamoto, and Hayashida are clinical proctors of transcatheter edge-to-edge repair for Abbott Medical and received speaker fees from Abbott Medical. Drs Asami and Kodama received speaker fees from Abbott Medical. Dr Yamaguchi is the clinical proctor of transcatheter edge-to-edge repair for Abbott Medical and received a lecture fee and scholarship donation from Abbott Medical. Dr Ohno received consultant, advisor, and speaker fees from Abbott Medical. The other authors report no conflicts.

Background: Little is known about the effects of left ventricular ejection fraction (LVEF) worsening after transcatheter edge-to-edge valve repair (TEER) for mitral regurgitation (MR)., Aims: This study investigated the predictors and clinical impact of LVEF worsening after TEER for primary MR (PMR) and secondary MR (SMR)., Methods: This study included 2,019 patients (493 with PMR and 1,526 with SMR) undergoing successful TEER (postprocedural MR grade ≤2+) in the OCEAN-Mitral registry. The patients were categorised into worsened LVEF (wEF), defined as a relative decrease of >12.9% in LVEF at discharge, and preserved LVEF (pEF). The serial changes in left ventricular (LV) function at 1 year were also evaluated., Results: Following TEER, 657 (32%) patients demonstrated wEF. The pEF group demonstrated both decreased left ventricular end-diastolic volumes (LVEDV) and end-systolic volumes (LVESV), and the wEF group showed significantly increased LVESV at discharge. Higher LVEF, larger LVEDV, higher B-type natriuretic peptide levels, and moderate/severe aortic regurgitation predicted wEF. Compared with baseline, the wEF group still demonstrated lower LVEF (46% to 43%; p<0.001) but significantly increased stroke volume (48 mL to 53 mL; p=0.001) at 1 year. The incidence of death or heart failure hospitalisation was similar between the wEF and pEF groups (hazard ratio 1.14, 95% confidence interval: 0.72-1.80; p=0.84) and also in patients with PMR and SMR., Conclusions: LVEF worsening after TEER was not uncommon and was caused by the increased LVESV. LV volumes and some patient-specific factors predicted worsened LVEF which was not associated with long-term clinical outcomes. OCEAN-Mitral registry: UMIN-CTR ID: UMIN000023653.

The MitraClip G4 device has controlled gripper actuation (CGA) system, which allows the anterior and posterior grippers operate separately in transcatheter edge-to-edge repair (TEER). We investigated the indications and outcomes of the use of CGA system during TEER for significant mitral regurgitation (MR). We reviewed 158 patients undergoing TEER with MitraClip G4 from September 2020 to July 2023. The CGA indications were: (1) for grasping and (2) for leaflet insertion confirmation. Leaflet grasping was completed with CGA in 18 patients (11 and 7 patients for grasping and leaflet insertion confirmation, respectively). Patients with flail leaflets or coaptation gap more frequently required CGA, indicating more complex mitral valve anatomy. The procedural success and adverse event rates (death, leaflet tear and single leaflet device attachment) were not different between the CGA and non-CGA groups. In patients requiring CGA, single leaflet device attachment was observed in 1 patient and leaflet tear in 1 patient during follow-up. In these two cases, CGA was required for grasping, and the clip was moved over a large distance (6.5 and 12.4 mm, respectively). In patients who had undergone CGA for confirmation, no device-related adverse event or MR recurrence was noted. In patients with complex mitral valve anatomy, CGA may be a safe and effective method for confirming leaflet insertion. It should be noted that when using CGA for leaflet grasping, especially when the clip is moved significantly, attention should be paid to leaflet adverse events., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Patients with nonvalvular atrial fibrillation (AF) not suitable for long-term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC) using the WATCHMAN device. The safety and efficacy of WATCHMAN-FLX (WM-FLX) compared with WATCHMAN-2.5 (WM-2.5), particularly in Asian populations, is unknown., Methods: We evaluated the background, procedure, and clinical outcomes of 199 patients who underwent LAAC between September 2019 and December 2022 and compared WM-2.5 (72 patients) with WM-FLX (127 patients)., Results: The mean age was 76 years, with 128 men, and 100 had nonparoxysmal AF (non-PAF). The mean CHA 2 DS 2 -VASc, and HAS-BLED were 5.1, and 3.2 points, respectively. WM-FLX group demonstrated a shorter procedure time than WM-2.5 group (50 vs. 42 min, p = 0.001). The WM-FLX group demonstrated no procedural-related acute cardiac tamponade, which was significantly low (5.6% vs. 0%, p = 0.02), and a significantly higher rate of complete seal at 45-day (63% vs. 80%, p = 0.04). WM-FLX group had a significantly higher cumulative 1-year incidence of device-related thrombosis (DRT) than WM-2.5 group (3.4% vs. 7.0%, Log-rank p = 0.01). Univariate analysis identified two DRT risk factors in the WM-FLX group: non-PAF (odds ratio [OR] 7.72; 95% confidence interval [CI] 1.20-48.7; p = 0.04), and 35-mm device (OR 5.13; 95% CI 1.31-19.8; p = 0.02)., Conclusions: WM-FLX significantly improved the procedural quality and safety of LAAC. However, DRT remains an important issue even in the novel LAAC device, being a hazard for patients with high DRT risk, such as having non-PAF and using 35-mm devices., (© 2024 Wiley Periodicals LLC.)

The Academic Research Consortium (ARC) recently published a definition of patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. However, the prevalence of the ARC-HBR criteria in patients undergoing endovascular therapy (EVT) for femoropopliteal arterial lesions has not been thoroughly investigated. The study population comprised 165 patients undergoing initial EVT for femoropopliteal lesions between June 2018 and June 2020. They were divided into two groups according to the ARC-HBR criteria. The primary end point was a composite of all-cause death, Bleeding Academic Research Consortium type 3 or 5 bleeding, and target lesion revascularization (TLR) within 2 years of EVT. The 165 patients were divided into two groups: 125 (75.8%) patients at HBR (HBR group) and 40 (24.2%) patients at no HBR (non-HBR group). The cumulative incidence of the primary endpoint was significantly higher in the HBR group than in the non-HBR group (40.6% vs. 0%, log-rank p < 0.001). The HBR group had a significantly higher risk of all-cause death, major bleeding, and TLR than the non-HBR group (25.2% vs. 0%, log-rank p = 0.004, 13.9% vs. 0%, log-rank p = 0.047, 16.8% vs. 0%, log-rank p = 0.035). Most patients with peripheral artery disease were classified as HBR patients, and HBR patients were at higher risk of death, major bleeding, and TLR than non-HBR patients., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: There have been still limited data on the transition of management strategies and clinical outcomes after introduction of direct oral anticoagulant (DOAC) for cancer-associated venous thromboembolism (VTE) in the real-world clinical practice., Methods: Using the 2 series of multicenter COMMAND VTE registries in Japan enrolling consecutive patients with acute symptomatic VTE, we compared 695 patients with cancer-associated VTE in the Registry-1 of the warfarin era and 1507 patients in the Registry-2 of the DOAC era., Results: Regarding oral anticoagulation therapy, 576 patients (82.9 %) in the Registry-1 received warfarin, whereas 1119 patients (79.6 %) in the Registry-2 received DOACs. The cumulative 3-year incidence of discontinuation of anticoagulation was not significantly different between the 2 registries (56.7 % vs. 62.7 %, P = 0.11). The cumulative 5-year incidence of recurrent VTE was significantly lower in the Registry-2 than in the Registry-1 (17.7 % vs. 10.1 %, P < 0.001). The cumulative 5-year incidence of major bleeding was significantly lower in the Registry-2 than in the Registry-1 (26.6 % vs. 20.4 %, P = 0.045). The proportion of gastrointestinal bleeding numerically increased from the Registry-1 to the Registry-2 (46.7 % and 49.5 %), whereas that of intracranial bleeding numerically decreased from the Registry-1 to the Registry-2 (17.1 % and 14.1 %)., Conclusions: In the current historical comparison of cancer-associated VTE between the 2 large real-world registries, there was a striking change in the treatment strategies with decreased risks of recurrent VTE and major bleeding in the DOAC era compared with those in the warfarin era, while there seemed to be unmet needs of DOAC-related gastrointestinal bleeding., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm UNIQUE IDENTIFIER: UMIN000044816., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo and grant support from Bayer Healthcare and Daiichi-Sankyo. Dr. Morimoto reports lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Dr. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi-Sankyo. All other authors report that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Contrast media are generally necessary for transcatheter left atrial appendage closure (LAAC), however, it should be avoided in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the safety and feasibility of contrast-free LAAC with WATCHMAN FLX device for patients with CKD. Among 141 patients undergoing LAAC using the WATCHMAN FLX between May 2021 and March 2023, we performed LAAC without contrast media in 10 patients. Procedural and follow-up results were evaluated. The device size was selected based on the transesophageal echocardiographic (TEE) measurements. The device shape was assessed by fluoroscopy, and the device position was adjusted by TEE images. The mean age was 78 ± 4.9 years, CHADS 2 score was 3.2 ± 1.1, and the estimated glomerular filtration rate (eGFR) was 28 ± 12 mL/min/1.73m 2 . The procedure was completed without contrast media in ten patients. Partial recapture of the device was required in four patients, but the initially selected device was finally implanted in all patients. Mean procedure time was significantly shorter in the contrast-free LAAC than in the contrast-use LAAC (41.6 ± 14.1 min vs 30.3 ± 7.6 min, p = 0.01). Postprocedural eGFR did not change from baseline, and there were no adverse events during the hospital stay. Follow-up TEE or cardiac computed tomography performed within 3 months after the procedure revealed no device-related thrombus or peri-device leak > 3 mm, and oral antithrombotic therapy was discontinued in all patients. Our experience shows that contrast-free LAAC using the WATCHMAN FLX device was safe and feasible. Non-contrast LAAC is one of the therapeutic options for patients with severe CKD., (© 2023. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events., Conclusions: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.

Background: There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era., Objectives: To investigate the status of cancer-associated VTE in the DOAC era., Methods: This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without., Results: The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66)., Conclusions: The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo and grant support from Bayer Healthcare and Daiichi-Sankyo. Dr. Morimoto reports lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray and manuscript fees from Bristol-Myers Squibb and Kowa; he was on the advisory board for Sanofi. Dr. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi-Sankyo. Dr. Ogihara received research funding from Bayer Healthcare. Dr. Koitabashi received lecture fees from Bayer Healthcare and grant support from Pfizer. All other authors reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Three C(27) bile acids were found to be major biliary bile acids in the capuchinbird (Perissocephalus tricolor) and bare-throated bellbird (Procnias nudicollis), both members of the Cotingidae family of the order Passeriformes. The individual bile acids were isolated by preparative RP-HPLC, and their structures were established by RP-HPLC, LC/ESI-MS/MS and NMR as well as by a comparison of their chromatographic properties with those of authentic reference standards of their 12α-hydroxy derivatives. The most abundant bile acid present in the capuchinbird bile was the taurine conjugate of C(27) (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid, a diastereomer not previously identified as a natural bile acid. The four diastereomers of taurine-conjugated (24ξ,25ξ)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid could be distinguished by NMR and were resolved by RP-HPLC. The RRT of the diastereomers (with taurocholic acid as 1.0) were found to be increased in the following order: (24R,25R)<(24S,25R)<(24S,25S)<(24R,25S). Two epimers (25R and 25S) of C(27) 3α,7α-dihydroxy-5β-cholestan-27-oic acid were also present (as the taurine conjugates) in both bird species. Epimers of the two compounds could be distinguished by their NMR spectra and resolved by RP-HPLC with the (25S)-epimer eluting before the (25R)-epimer. Characterization of the taurine-conjugated (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid and two epimers (25R and 25S) of 3α,7α-dihydroxy-5β-cholestan-27-oic acid should facilitate their detection in peroxisomal disease and inborn errors of bile acid biosynthesis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The biliary bile salts of the medaka, the Japanese rice fish (Oryzias latipes) were isolated and identified. Only bile acids were present, and all were N-acylamidated with taurine. Three bile acids, constituting 98% of total bile acids, were isolated by chromatography and their structure inferred from their properties compared to those of synthetic standards when analyzed by liquid chromatographytandem mass spectrometry. The dominant bile acid was the 25R-epimer (82%) of 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-oic acid. The 25S-epimer was also present (11%), as was cholic acid (5%). Complete (1)H and (13)C NMR signal assignments of the C-25 epimers were made by using a combination of several 1D- and 2D-NMR techniques. The (1)H and (13)C NMR chemical shifts and spectral patterns of the hydrogen and carbon atoms, being close to the asymmetric centered at C-25, provided confirmatory evidence in that they distinguished the two epimeric diastereomers. The medaka is the first fish species identified as having C(27) biliary bile acids as dominant among its major bile salts.

The chemical structures of the three major bile acids present in the gallbladder bile of the Red-winged tinamou (Rhynchotus rufescens), an early evolving, ground-living bird related to ratites, were determined. Bile acids were isolated by preparative reversed-phase HPLC. Two of the compounds were identified as the taurine N-acylamidates of 25R-3alpha,7alpha-dihydroxy-5beta-cholestan-27-oic acid (constituting 22% of biliary bile acids) and 25R-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-oic acid (constituting 51%). The remaining compound, constituting 21% of biliary bile acids, was an unknown C27 bile acid. Its structure was elucidated by LC/ESI-MS/MS and NMR and shown to be the taurine conjugate of 25R-1beta, 3alpha, 7alpha-trihydroxy-5beta-cholestan-27-oic acid, a C27 trihydroxy bile acid not previously reported. Although C27 bile acids with a 1beta-hydroxyl group have been identified as trace bile acids in the alligator, this is the first report of a major biliary C27 bile acid possessing a 1beta-hydroxyl group.

Complete 1H and 13C resonance assignments were made for a new type of 3 beta,7 beta-dihydroxy-5-cholen-24-oic acid doubly conjugated with sulfuric acid at C-3 and N-acetylglucosamine at C-7 and its glycine- and taurine-amidated triple-conjugates by the combined use of several homonuclear and heteronuclear shift-correlated 2D NMR techniques. The effects of sulfation at C-3, N-acetylglucosaminidation at C-7, and aminoacyl amidation at C-24 on the 1H and 13C chemical shifts and signal multiplicity were clarified. The shielding data serving to characterize each of the bile acid multi-conjugates are also discussed.

A method is reported for the preparation of the C-24 carboxyl-linked beta-D-galactopyranosides of lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic acids, two of which were recently identified as a novel type of the metabolites of bile acids excreted in human urine. Direct esterification (galactosidation) of the unprotected bile acids with 2,3,4,6-tetra-O-benzyl-D-galactopyranose in the presence of 2-chloro-1,3,5-trinitrobenzene as a coupling agent and subsequent hydrogenolysis of the resulting benzyloxy-protected bile acid 24-beta-D-galactopyranosides over 10% palladium on charcoal under atmospheric pressure afforded the title compounds. The structures of the bile acid acyl galactosides were confirmed by measuring several (1)H-(1)H and (1)H-(13)C shift correlated 2D NMR.

Hirschsprung disease (HSCR) is sometimes associated with a set of characteristics including mental retardation, microcephaly, and distinct facial features, but the gene mutated in this condition has not yet been identified. Here we report that mutations in SIP1, encoding Smad interacting protein-1, cause disease in a series of cases. SIP1 is located in the deleted segment at 2q22 from a patient with a de novo t(2;13)(q22;q22) translocation. SIP1 seems to have crucial roles in normal embryonic neural and neural crest development.

Five patients with common variable immunodeficiency treated in our hospital between December 1979 and December 1990 were given six kinds of intravenous immunoglobulin preparations (pepsin treated, S-sulfonated, polyethylene glycol treated, pH4 treated, alkylated, and pH4.25 formulation preparation) for replacement therapy. Duration of the therapy ranged from 7.6 to 11 years. Incidences of fever and acute infections were variable among patients, but no significant differences were seen in the incidences among periods given each preparation. Three cases revealed abnormal pulmonary functions in tests. Adverse reactions were rarely seen in our study periods, and no severe reactions were observed. No significant differences were seen in incidences of adverse reactions. Postinfusion levels of serum complement slightly decreased from preinfusion levels. However, the decrease in complement was not related to any adverse reaction. No long-term complications such as transmission of hepatitis have been observed. Our data suggest that no obvious differences exist between the efficacy and safety of each IVIG preparation. Differences of efficacy of IVIG replacement therapy may be due to the variable pathophysiology of each patient.

Three patients with common variable immunodeficiency (CVID) were analyzed for translation from mu mRNA by the cell-free translation method and for expression of mu mRNA by northern blotting. In cases 1 and 2, the mu chain was not detected in the products by cell-free translation nor was mu mRNA detected by northern blotting. In case 3, mu mRNA was detected at a low level. This suggests that the disorders occur between rearrangement of the Ig genes and transcription of the C mu gene in cases 1 and 2, and that the functions of rearrangement and transcription are qualitatively preserved to a certain degree in case 3. Thus, the pathogeneses of CVID are variable and more research on regulatory mechanisms of B cell development is necessary to understand each case of CVID.

Spherical virus particles were purified from larval striped jack (Pseudocaranx dentex) with nervous necrosis. The virus consists of nonenveloped particles, about 25 nm in diameter, and contains two single-stranded, positive-sense RNA molecules with molecular weights of 1.01 x 10(6)Da (RNA 1) and 0.49 x 10(6)Da (RNA 2), respectively. The RNAs do not have poly(A) sequences at the 3' terminus. Virus structural proteins consist of two proteins with molecular weights of 42 and 40 kDa. When translated into cell-free extracts of rabbit reticulocytes, RNA 1 directed the synthesis of the 1a protein (100 kDa), whereas RNA 2 synthesized the 2a protein (42 kDa), which is probably the coat protein of the virus, and a polypeptide of 40 kDa which appears to be the processed form of the 42-kDa protein. Under electron microscopic observation, the virus particles were found in the tissues of the central nervous system of the affected larval striped jack. From morphological and biochemical properties of the virus, we identified this virus as a new member of the family of Nodaviridae and designated it striped jack nervous necrosis virus.

The proliferative responses and the immunoglobulin production of peripheral blood mononuclear cells to pokeweed mitogen were dose-dependently suppressed by sulfonated intravenous immunoglobulin (IVIG), polyethylene glycol-treated IVIG, pH 4-treated IVIG, or human gamma-globulin, but they were not or only slightly suppressed by human serum albumin or pepsin-treated IVIG. Moreover, the suppression of immunoglobulin production by sulfonated IVIG, polyethylene glycol-treated IVIG, or pH 4-treated IVIG was seen in the cases in which B cells preincubated with IVIGs were cocultured with T cells and monocytes preincubated with or without IVIGs and in the cases in which monocytes preincubated with IVIGs were cocultured with T cells and B cells preincubated with or without IVIGs. However, in the cases in which only T cells were preincubated with IVIGs, immunoglobulin production was not suppressed. The suppression of the monocyte function by IVIGs tended to be less than the suppression of the B-cell function by IVIGs. Moreover, the suppression by IVIGs was blocked by anti-human IgG Fc. Our results suggest that IVIGs suppress the immunoglobulin production of lymphocytes through suppression of the B-cell function and the antigen presenting-cell function by attachment of IVIGs to Fc receptors of B-cell membranes and antigen presenting-cell membranes.