The GORE EXCLUDER Iliac Branch Endoprosthesis (IBE; W. L. Gore and Associates, Flagstaff, AZ, USA) applicability is limited by the aorto-iliac length (AOL). The shortage may be a major exclusion ...criterion. An 85-year-old male presented with an abdominal aortic and left common iliac arterial aneurysm. The left-side AOL was 146-mm, which was deemed 19-mm too short for IBE usage. To increase implantation length, the contra-lateral connection stent graft was deployed along the implantation line, wound half-circumferentially around the ipsilateral limb. Any form of endoleak, limb occlusion, and device migration has not been observed for twelve months.
The medical uses of three-dimensional (3D) printing are evolving at a rapid pace. The current roles and the future outlooks of this technology for physician-modified endovascular graft (PMEG) in ...patients with juxtarenal aneurysm are discussed. Fenestrations of PMEG are designed taking into account the geometry of the stent graft. Designing of such stent grafts is extremely complicated, especially when PMEG is planned for the angulated portion of the aorta. A 3D model enables the designing of branch fenestrations, with consideration for the geometrical adaptation of the stent graft in a complex aortic anatomy. With the aid of 3D-printing technology, patients with juxtarenal aortic pathologies can be treated using fenestrated stent grafts, preserving the vital organ circulation and securing a robust length of proximal sealing zone.
We previously found that genetic polymorphism in cytochrome P450 2A6 (CYP2A6) is one of the potential determinants of tobacco-related lung cancer risk. It has been reported that the plasma ...concentration of cotinine, a major metabolite of nicotine, in carriers of wild-type alleles of CYP2A6 is considerably higher than that in carriers of null or reduced-function alleles of CYP2A6, raising the possibility that cotinine plays an important role in the development of lung cancer. As a novel mechanism of lung tumorigenesis mediated by CYP2A6, we investigated the effects of cotinine on the suppression of apoptosis and promotion of lung tumor growth. In human lung adenocarcinoma A549 cells, cotinine inhibited doxorubicin-induced cell death by suppressing caspase-mediated apoptosis. Enhanced phosphorylation of Akt, a key factor responsible for cell survival and inhibition of apoptosis, was detected after cotinine treatment. These data suggest that cotinine suppresses caspase-mediated apoptosis induced by doxorubicin through activation of the PI3K/Akt pathway. Furthermore, we clarified that cotinine significantly facilitated tumor growth in the Lewis lung cancer model and accelerated development of lung adenomas induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mice. We herein propose that cotinine induces tumor promotion by inhibiting apoptosis and enhancing cellular proliferation, thus underlining the importance of CYP2A6 in tobacco-related lung tumorigenesis.
Background:Very limited data exist on the outcomes of transcatheter aortic valve implantation (TAVI) since Japanese marketing approval of the first TAVI device.Methods and Results:The Kyoto ...University-related hospital Transcatheter Aortic Valve Implantation (K-TAVI) registry includes prospectively collected data from 6 participating hospitals in Japan. We included 302 patients with severe aortic stenosis who underwent TAVI using the SAPIEN XT balloon-expandable valve via transfemoral (TF; n=203, 67%) or transapical (TA; n=99, 33%) approach between October 2013 and September 2015. Device success rate, based on the Valve Academic Research Consortium-2 criteria, was very high in the TF (97.0%) and TA (99.0%) groups. The 30-day mortality rates were 1.5% and 1.0% in the TF and TA groups, respectively. Major complications included stroke (transient or persistent: 2.3%), annulus rupture (1.0%), coronary intervention (1.0%), major vascular complications (1.7%), and permanent pacemaker implantation (5.4%). The procedure times of the post-proctoring period (n=210) were decreased compared with those of the proctoring period (n=89) without affecting the clinical outcomes. The survival rates at 6 and 12 months were 96.9% and 92.5% in the TF group, and 93.9% and 91.8% in the TA group, respectively.Conclusions:The K-TAVI registry data revealed that the early outcomes of TAVI using the SAPIEN XT were favorable in real-world Japanese patients.
Injury to the right coronary artery (RCA) is a rare complication of tricuspid annuloplasty. We report a patient who developed right ventricular (RV) infarction, because of tricuspid annuloplasty, and ...review management options.
Purpose
Although the outcomes of aortic arch surgery have improved, stroke remains one of the most devastating complications. Therefore, identification of true risk factors and understanding the ...pathogenesis of intraoperative stroke are necessary to decrease its occurrence.
Methods
From January 2002 to December 2010, a total of 251 consecutive patients underwent aortic arch surgery under deep hypothermic circulatory arrest and antegrade selective cerebral perfusion in our hospital. Hemiarch replacement cases were excluded. Of the remaining patients, 190 elective cases that could be reviewed with full perioperative clinical data were analyzed. Strokes were classified into three subtypes according to their distribution on imaging studies: multiple-embolism type, hypoperfusion type, and solitary-embolism type.
Results
Operative death occurred in 1.1% of patients (2/190), and aortic arch surgery-related in-hospital death occurred in 5.3%. Among the 188 survivors, intraoperative strokes occurred in 5.9%. Multiple-embolism, hypoperfusion type, and solitary-embolism stroke occurred in 2.7%, 2.1%, and 1.6%, respectively. Multivariate analysis revealed that the risk factor for multiple-embolism stroke was high-grade atheroma in the ascending aorta
P
< 0.001, odds ratio (OR) 118.0, and that for hypoperfusion type stroke was prolonged brain ischemia time over 120 min (
P
= 0.004, OR 31.5). No significant risk factor was found for solitary-embolism stroke.
Conclusion
Intraoperative strokes during elective aortic arch surgery under deep hypothermic circulatory arrest and antegrade selective cerebral perfusion are strongly influenced by the presence of a high-grade atheroma in the ascending aorta and prolonged brain ischemia time. The results suggest that these are key issues to reduce stroke in aortic arch surgery.
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•We developed a simple pharmacokinetic (PBPK) model of molinate.•Rat or mouse PBPK model of molinate was scaled to human model to predict in humans.•Molinate elimination in humans was ...estimated to be slow compared with those in rats.•Concentrations of molinate were evaluated by chimeric mice with humanized liver.•The simplified human PBPK modeling is useful for risk evaluation of molinate.
To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.
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