Thoracic endovascular aneurysm repair in Japan: Experience with fenestrated stent grafts in the treatment of distal arch aneurysms

ObjectivesIn the West, stent grafts for endovascular repair of thoracic aortic aneurysms have been commercially available for several years, whereas in Japan, a manufactured stent graft was not approved for this application until March 2008. Nevertheless, endovascular thoracic intervention began to be performed in Japan in the early 1990s, with homemade devices used in most cases. Many researchers have continued to develop homemade devices. We have participated in joint design and assessment efforts with a stent graft manufacturer, focusing primarily on fenestrated stent grafts used in repairs at the distal arch, a site especially prone to aneurysm.MethodsFrom 1995 to February 2008, we performed about 1100 endovascular procedures to treat thoracic aortic aneurysms and 682 cases were performed at Tokyo Medical University. In 435 out of 682 the aneurysm was located in the area from the distal arch to the proximal descending aorta. Fenestrated stent grafts were inserted in 288 cases. Computed tomography scans were performed at 3, 6, and 12 months postoperatively and annually thereafter.ResultsThe initial success rate in the entire series was 95.2%. Complications included 26 cerebral infarctions (3.8%), six of which (0.9%) resulted in serious paralysis and changes in consciousness. Among patients who received fenestrated stent grafts, paraplegia occurred in 2.6%, aortic injury in 1.2%, and iliofemoral artery injury in 6.0%. No complications resulted from occlusion of aortic arch branches. At ≥2 years after intervention, aneurysm diameter was reduced in 62% of patients, 33% had no change, and 5% had a diameter enlargement. The stent graft complication rate during follow-up was 8.4%, the device fracture rate was 1.4%, and the device migration rate was 7%. The 5-year survival rate was 62.4%, with follow-up in 96.8% of the patients.ConclusionEndovascular repair has promising results in the descending thoracic aortic region, although some stent grafts and their delivery systems can still be improved. Additional commercial developments and available stent grafts designed for use in the distal arch are urgently needed

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

開殻系ヘキサフィリンの研究

京都大学0048新制・課程博士博士(理学)甲第16648号理博第3760号新制||理||1544(附属図書館)29323京都大学大学院理学研究科化学専攻(主査)教授 大須賀 篤弘, 教授 林 民生, 教授 丸岡 啓二学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDA

Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice

Background The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor‐kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteoprotegerin affects aortic structural integrity in angiotensin II (Ang II)‐induced hypertension. Methods and Results Mortality was higher (P<0.0001 by log‐rank test) in 8‐week‐old male homozygotes of osteoprotegerin gene‐knockout mice given subcutaneous administration of Ang II for 28 days, with an incidence of 21% fatal aortic rupture and 23% aortic dissection, than in age‐matched wild‐type mice. Ang II‐infused aorta of wild‐type mice showed that osteoprotegerin immunoreactivity was present with proteoglycan. The absence of osteoprotegerin was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with increased periostin expression and soluble receptor activator of nuclear factor‐kappa B ligand concentrations. PEGylated human recombinant osteoprotegerin administration decreased all‐cause mortality (P<0.001 by log‐rank test), the incidence of fatal aortic rupture (P=0.08), and aortic dissection (P<0.001) with decreasing numbers of elastin breaks, periostin expressions, and soluble receptor activator of nuclear factor‐kappa B ligand concentrations in Ang II‐infused osteoprotegerin gene‐knockout mice. Conclusions These data suggest that osteoprotegerin protects against aortic rupture and dissection in Ang II‐induced hypertension by inhibiting receptor activator of nuclear factor‐kappa B ligand activity and periostin expression

Cobalt–Carbon Bond Formation Reaction via Ligand Reduction of Porphycene–Cobalt(II) Complex and Its Noninnocent Reactivity

The interesting redox properties and reactivity of metalloporphycene have been studied for decades; however, the detailed experimental investigation on the reactivity and reaction mechanism under inert condition combined with theoretical calculations had not been performed so far. In this study, the novel reactivity of the reduced form of the cobalt porphycene with alkyl halides to form cobalt–carbon (Co–C) bonds was revealed. Under electrochemical reductive conditions, not the central cobalt, but the ligand was reduced and reacted with alkyl halides to afford the cobalt–alkyl complexes under N₂ atmosphere in a glovebox. The reaction mechanism was clarified by the combination of experimental and theoretical studies that the porphycene ligand works as a noninnocent ligand and allows the S_N2-type Co–C bond formation. This result provides us the possibility of the reaction triggered by the reduction of ligand with macrocyclic π-conjugated system, not by the reduction of metal

Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer

Although a therapeutic response to neoadjuvant chemoradiotherapy (NACRT) is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/β-catenin signal is known to be crucial for the tumorigenesis of colorectal cancer. This study aimed to investigate the association of Wnt/β-catenin signal activation with a pathological response to NACRT. The immunohistochemical expression of nuclear and membranous β-catenin was analyzed in biopsy samples obtained from 60 patients with locally advanced rectal cancer who received curative surgery following NACRT. The association of Wnt/β-catenin signal activation with their clinical outcomes was investigated. Notably, the body mass index of these patients was significantly higher in the low nuclear β-catenin expression group. Moreover, patients in the high nuclear β-catenin expression group tended to have more advanced disease and a higher rate of positive vascular invasion than those in the low expression group. Furthermore, the rate of good histological responses was significantly higher in the low nuclear β-catenin expression group (72% vs. 37.1%, p n = 9) than in other individuals (n = 51) (p = 0.093 and p = 0.214, respectively). Activation of the Wnt/β-catenin signal pathway represented by nuclear β-catenin accumulation was significantly associated with a poor response to NACRT in patients with rectal cancer. Analysis of nuclear β-catenin accumulation before starting treatment might help predict the therapeutic response to NACRT

Cobalt–Carbon Bond Formation Reaction via Ligand Reduction of Porphycene–Cobalt(II) Complex and Its Noninnocent Reactivity

The interesting redox properties and reactivity of metalloporphycene have been studied for decades; however, the detailed experimental investigation on the reactivity and reaction mechanism under inert condition combined with theoretical calculations had not been performed so far. In this study, the novel reactivity of the reduced form of the cobalt porphycene with alkyl halides to form cobalt–carbon (Co–C) bonds was revealed. Under electrochemical reductive conditions, not the central cobalt, but the ligand was reduced and reacted with alkyl halides to afford the cobalt–alkyl complexes under N₂ atmosphere in a glovebox. The reaction mechanism was clarified by the combination of experimental and theoretical studies that the porphycene ligand works as a noninnocent ligand and allows the S_N2-type Co–C bond formation. This result provides us the possibility of the reaction triggered by the reduction of ligand with macrocyclic π-conjugated system, not by the reduction of metal