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Abstract Aortic anomaly in which a right-sided aortic arch associated with Kommerell's diverticulum and aberrant left subclavian artery is rare. The present report describes a patient with type-B aortic dissection accompanying aortic anomalies consisting of right-sided aortic arch and the left common carotid and left subclavian artery arising from Kommerell's diverticulum. As dissecting aortic aneurysm diameter increased rapidly, Single-stage surgical repair of extensive thoracic aorta was performed through median sternotomy and right posterolateral fifth intercostal thoracotomy, yielding favorable results. Our surgical procedures are discussed.

Abstract We herein present a 60 years old woman with Takayasu arteritis and an extensive thoracic aortic aneurysm who initially underwent a total aortic arch replacement. Then, in the second stage, thoracic endovascular aortic repair was performed using the elephant trunk graft as the proximal landing zone at four weeks after aortic arch repair. The postoperative course was relatively uncomplicated, but a type II endoleak was noted. Currently, about 5 years postoperatively, the slight type II endoleak from intercostal artery persists, but aneurism dilatation has not been noted, so the patient is being followed up.

Background: The 3Rs (Reduction, Refinement, Replacement) principle is driving the need for alternative methods in animal testing. Despite advancements in in vitro testing, complex systemic toxicity tests still necessitate in vivo approaches. The aim of this study was to develop a developmental toxicity test protocol using the Iberian ribbed newt ( Pleurodeles waltl ) as a model organism, integrating AI image analysis for embryo selection to improve test accuracy and reproducibility., Methods: We established a developmental toxicity test protocol based on the zebrafish test. Gonadotropin was administered to induce ovulation, and in vitro fertilization was performed. Embryos were imaged at 5-6 and 6-7 h post-fertilization. AI image analysis was utilized to assess embryo viability. The test chemical was administered 24-48 h post-fertilization, and morphological changes were observed daily until day 8. Additionally, a time-lapse photography system was constructed to monitor embryonic development., Results: Out of 24 cultured embryos, 75% developed normally to the late tail bud stage or initial hatching stage, whereas 25% experienced developmental arrest or death. AI image analysis achieved high accuracy in classifying embryos, with overall accuracies of 92.0% and 92.9% for two learning models. The AI system demonstrated higher precision in the selection of viable embryos compared to visual inspection., Conclusion: The Iberian ribbed newt presents a viable alternative model for developmental toxicity testing, adhering to the 3Rs principles. The integration of AI image analysis substantially enhances the accuracy and reproducibility of embryo selection, providing a reliable method for evaluating developmental toxicity in pharmaceuticals., Competing Interests: The authors declare no conflict of interest., (©2024 Tottori University Medical Press.)

The induction of tissue-specific vessels in in vitro living tissue systems remains challenging. Here, we directly differentiated human pluripotent stem cells into CD32b + putative liver sinusoidal progenitors (iLSEP) by dictating developmental pathways. By devising an inverted multilayered air-liquid interface (IMALI) culture, hepatic endoderm, septum mesenchyme, arterial and sinusoidal quadruple progenitors self-organized to generate and sustain hepatocyte-like cells neighbored by divergent endothelial subsets composed of CD32b low CD31 high , LYVE1 + STAB1 + CD32b high CD31 low THBD - vWF - , and LYVE1 - THBD + vWF + cells. Wnt2 mediated sinusoidal-to-hepatic intercellular crosstalk potentiates hepatocyte differentiation and branched endothelial network formation. Intravital imaging revealed iLSEP developed fully patent human vessels with functional sinusoid-like features. Organoid-derived hepatocyte- and sinusoid-derived coagulation factors enabled correction of in vitro clotting time with Factor V, VIII, IX, and XI deficient patients' plasma and rescued the severe bleeding phenotype in hemophilia A mice upon transplantation. Advanced organoid vascularization technology allows for interrogating key insights governing organ-specific vessel development, paving the way for coagulation disorder therapeutics.

Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming., Competing Interests: Declaration of interests A.K. and K.F. are co-inventors on a patent describing the method for producing human iPSCs from somatic cells using H1FOO-DD. K.F. is a co-founder and CEO of Heartseed Inc., and S.T., S. Yuasa, and K.F. own equity in Heartseed Inc. S.T. is an advisor of Heartseed Inc. J.K. and H.H. are employees and K.K. is a board member of ID Pharma Co., Ltd., without compensation relating to this study. S. Yamanaka is a scientific advisor to iPS Academia Japan without salary., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Reticular dysgenesis (RD) is a rare genetic disease caused by gene mutations in the ATP:AMP phosphotransferase, adenylate kinase 2 (AK2). Patients with RD suffer from severe combined immunodeficiency with neutrophil maturation arrest. Although hematopoietic stem cell transplantation can be a curative option, it is invasive, and complications of agranulocytosis-induced infection worsen the prognosis. Here, we report that the use of UK-5099, an inhibitor of the mitochondrial pyruvate carrier (MPC), on hemo-angiogenic progenitor cells (HAPCs) derived from AK2-deficient induced pluripotent stem cells improved neutrophil maturation. Reactive oxygen species (ROS) levels in AK2-deficient HAPCs remained unchanged throughout all experiments, implying that UK-5099 improved the phenotype without affecting ROS levels. Overall, our results suggest that the MPC is a potential therapeutic target for the treatment of neutrophil maturation defects in RD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Megumu K. Saito reports financial support was provided by Japan Agency for Medical Research and Development. Megumu K. Saito reports financial support was provided by Terumo Life Science Foundation. Megumu K. Saito reports financial support was provided by iPS Cell Research Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

COVID-19 is linked to endotheliopathy and coagulopathy, which can result in multi-organ failure. The mechanisms causing endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain elusive. Here, we developed an infection-competent human vascular organoid from pluripotent stem cells for modeling endotheliopathy. Longitudinal serum proteome analysis identified aberrant complement signature in critically ill patients driven by the amplification cycle regulated by complement factor B and D (CFD). This deviant complement pattern initiates endothelial damage, neutrophil activation, and thrombosis specific to organoid-derived human blood vessels, as verified through intravital imaging. We examined a new long-acting, pH-sensitive (acid-switched) antibody targeting CFD. In both human and macaque COVID-19 models, this long-acting anti-CFD monoclonal antibody mitigated abnormal complement activation, protected endothelial cells, and curtailed the innate immune response post-viral exposure. Collectively, our findings suggest that the complement alternative pathway exacerbates endothelial injury and inflammation. This underscores the potential of CFD-targeted therapeutics against severe viral-induced inflammathrombotic outcomes., Competing Interests: Declaration of interests N.S. and T.T. are patent holders associated with the technology described in this project., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A drain is often placed in the abdominal cavity for postoperative monitoring and early detection of complications such as rebleeding and pancreatic or bile leaks. Since determining the color of the drainage fluid is subjective, an objective method of judging color is needed., Methods: The hemoglobin concentration of the drainage fluid after gastrointestinal surgery was measured using the Hemato Check Module, a newly developed instrument capable of absorbance analysis with an optical sensor. The correlation between the results and those measured by an existing blood count measuring device (XN3000) was investigated., Results: A total of 215 specimens were analyzed in 43 patients. For the correlation analysis, there was a strong positive correlation with a correlation coefficient of 0.884 ( P < 0.001). The Hemato Check Module showed a clear proportional error compared to the XN3000., Conclusion: The Hemato Check Module was a convenient and accurate instrument for measuring hemoglobin concentration in waste fluid to determine the presence of blood., Competing Interests: Conflict of interest: We received funding for this study from Ishida Medical Co., Ltd., (©2023 Tottori University Medical Press.)

The potential of extrapulmonary ventilation pathways remains largely unexplored. Here, we assessed the enteral ventilation approach in hypoxic porcine models under controlled mechanical ventilation. 20 mL/kg of oxygenated perfluorodecalin (O 2 -PFD) was intra-anally delivered by a rectal tube. We simultaneously monitored arterial and pulmonary arterial blood gases every 2 min up to 30 min to determine the gut-mediated systemic and venous oxygenation kinetics. Intrarectal O 2 -PFD administration significantly increased the partial pressure of oxygen in arterial blood from 54.5 ± 6.4 to 61.1 ± 6.2 mmHg (mean ± SD) and reduced the partial pressure of carbon dioxide from 38.0 ± 5.6 to 34.4 ± 5.9 mmHg. Early oxygen transfer dynamics inversely correlate with baseline oxygenation status. SvO 2 dynamic monitoring data indicated that oxygenation likely originated from the venous outflow of the broad segment of large intestine including the inferior mesenteric vein route. Enteral ventilation pathway offers an effective means for systemic oxygenation, thus warranting further clinical development., Competing Interests: Y.Y., T.F.C.-Y., and T.T. are inventors for enteral ventilation and founder of EVA Therapeutics, Inc. T.F. and Y.Y. are scientific advisors for EVA Therapeutics, Inc., (© 2023 The Authors.)

Key Message: Homologous genes for the peptidoglycan precursor flippase MurJ, and peptidoglycan hydrolases: lytic transglycosylase MltB, and DD-carboxypeptidase VanY are required for chloroplast division in the moss Physcomitrella patens. The moss Physcomitrella patens is used as a model plant to study plastid peptidoglycan biosynthesis. In bacteria, MurJ flippase transports peptidoglycan precursors from the cytoplasm to the periplasm. In this study, we identified a MurJ homolog (PpMurJ) in the P. patens genome. Bacteria employ peptidoglycan degradation and recycling pathways for cell division. We also searched the P. patens genome for genes homologous to bacterial peptidoglycan hydrolases and identified genes homologous for the lytic transglycosylase mltB, N-acetylglucosaminidase nagZ, and LD-carboxypeptidase ldcA in addition to a putative DD-carboxypeptidase vanY reported previously. Moreover, we found a ß-lactamase-like gene (Pplactamase). GFP fusion proteins with either PpMltB or PpVanY were detected in the chloroplasts, whereas fusion proteins with PpNagZ, PpLdcA, or Pplactamase localized in the cytoplasm. Experiments seeking PpMurJ-GFP fusion proteins failed. PpMurJ gene disruption in P. patens resulted in the appearance of macrochloroplasts in protonemal cells. Compared with the numbers of chloroplasts in wild-type plants (38.9 ± 4.9), PpMltB knockout and PpVanY knockout had lower numbers of chloroplasts (14.3 ± 6.7 and 28.1 ± 5.9, respectively). No differences in chloroplast numbers were observed after PpNagZ, PpLdcA, or Pplactamase single-knockout. Chloroplast numbers in PpMltB/PpVanY double-knockout cells were similar to those in PpMltB single-knockout cells. Zymogram analysis of the recombinant PpMltB protein revealed its peptidoglycan hydrolase activity. Our results imply that PpMurJ, PpMltB and PpVanY play a critical role in chloroplast division in the moss P. patens., (© 2020. Springer Nature B.V.)

Background & Aims: Preclinical identification of compounds at risk of causing drug induced liver injury (DILI) remains a significant challenge in drug development, highlighting a need for a predictive human system to study complicated DILI mechanism and susceptibility to individual drug. Here, we established a human liver organoid (HLO)-based screening model for analyzing DILI pathology at organoid resolution., Methods: We first developed a reproducible method to generate HLO from storable foregut progenitors from pluripotent stem cell (PSC) lines with reproducible bile transport function. The qRT-PCR and single cell RNA-seq determined hepatocyte transcriptomic state in cells of HLO relative to primary hepatocytes. Histological and ultrastructural analyses were performed to evaluate micro-anatomical architecture. HLO based drug-induced liver injury assays were transformed into a 384 well based high-speed live imaging platform., Results: HLO, generated from 10 different pluripotent stem cell lines, contain polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway. Single cell RNA-seq profiling identified diverse and zonal hepatocytic populations that in part emulate primary adult hepatocytes. The accumulation of fluorescent bile acid into organoid was impaired by CRISPR-Cas9-based gene editing and transporter inhibitor treatment with BSEP. Furthermore, we successfully developed an organoid based assay with multiplexed readouts measuring viability, cholestatic and/or mitochondrial toxicity with high predictive values for 238 marketed drugs at 4 different concentrations (Sensitivity: 88.7%, Specificity: 88.9%). LoT positively predicts genomic predisposition (CYP2C9∗2) for Bosentan-induced cholestasis., Conclusions: Liver organoid-based Toxicity screen (LoT) is a potential assay system for liver toxicology studies, facilitating compound optimization, mechanistic study, and precision medicine as well as drug screening applications., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Organogenesis is a complex and interconnected process that is orchestrated by multiple boundary tissue interactions 1-7 . However, it remains unclear how individual, neighbouring components coordinate to establish an integral multi-organ structure. Here we report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enables retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut-midgut boundary organoids in the absence of extrinsic factors. Whereas transplant-derived tissues are dominated by midgut derivatives, long-term-cultured microdissected hepato-biliary-pancreatic organoids develop into segregated multi-organ anlages, which then recapitulate early morphogenetic events including the invagination and branching of three different and interconnected organ structures, reminiscent of tissues derived from mouse explanted foregut-midgut culture. Mis-segregation of multi-organ domains caused by a genetic mutation in HES1 abolishes the biliary specification potential in culture, as seen in vivo 8,9 . In sum, we demonstrate that the experimental multi-organ integrated model can be established by the juxtapositioning of foregut and midgut tissues, and potentially serves as a tractable, manipulatable and easily accessible model for the study of complex human endoderm organogenesis.

Human organoid systems recapitulate in vivo organ architecture yet fail to capture complex pathologies such as inflammation and fibrosis. Here, using 11 different healthy and diseased pluripotent stem cell lines, we developed a reproducible method to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibit transcriptomic resemblance to in vivo-derived tissues. Under free fatty acid treatment, organoids, but not reaggregated cocultured spheroids, recapitulated key features of steatohepatitis, including steatosis, inflammation, and fibrosis phenotypes in a successive manner. Interestingly, an organoid-level biophysical readout with atomic force microscopy demonstrated that organoid stiffening reflects the fibrosis severity. Furthermore, organoids from patients with genetic dysfunction of lysosomal acid lipase phenocopied severe steatohepatitis, rescued by FXR agonism-mediated reactive oxygen species suppression. The presented key methodology and preliminary results offer a new approach for studying a personalized basis for inflammation and fibrosis in humans, thus facilitating the discovery of effective treatments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nakajo-Nishimura syndrome (NNS) is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of the PSMB8 gene. Although dysfunction of the immunoproteasome causes various cellular stresses attributed to the overproduction of inflammatory cytokines and chemokines in NNS, the underlying mechanisms of the autoinflammation are still largely unknown. To investigate and understand the mechanisms and signal pathways in NNS, we established a panel of isogenic pluripotent stem cell (PSC) lines with PSMB8 mutation. Activity of the immunoproteasome in PSMB8-mutant PSC-derived myeloid cell lines (MT-MLs) was reduced even without stimulation compared with non-mutant-MLs. In addition, MT-MLs showed an overproduction of inflammatory cytokines and chemokines, with elevated reactive oxygen species (ROS) and phosphorylated p38 MAPK levels. Treatment with p38 MAPK inhibitor and antioxidants decreased the abnormal production of cytokines and chemokines. The current PSC model revealed a specific ROS-mediated inflammatory pathway, providing a platform for the discovery of alternative therapeutic options for NNS and related immunoproteasome disorders., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for their clinical application. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrate that the directed switching of defined ECMs robustly yields highly-purified (>95%) endothelial progenitor cells (PSC-EPCs) without cell sorting from hPSCs in an integrin-laminin axis-dependent manner. Single-cell RNA-seq analysis revealed that LM411-E8 resolved intercellular transcriptional heterogeneity and escorted the progenitor cells to the appropriate differentiation pathway. The PSC-EPCs gave rise to functional endothelial cells both in vivo and in vitro. We therefore propose that sequential switching of defined matrices is an important concept for guiding cells towards desired fate.

We have elucidated the cooperative stabilization of proteins by sugars, amino acids, and other protein-stabilizing agents using a new and simple assay system. Our system determines the protein-stabilizing ability of various compounds by measuring their ability to protect hemoglobin from denaturation. Hemoglobin denaturation was readily measured by quantitative changes in its ultraviolet-visible absorption spectrum. The efficiency of our assay was confirmed using various sugars such as trehalose and sucrose that are known to be good protein stabilizers. We have also found that mixtures of two different types of protein stabilizers resulted in a cooperative stabilizing effect on protein.

Aim: The aim of this paper was to investigate the growth rate of abdominal aortic aneurysms (AAA) in Japanese patients., Methods: We retrospectively studied patients conservatively followed with infrarenal AAA in terms of AAA diameter measured using computed tomography (CT) in our hospital between 1999 and 2009. The AAA surgery criterion in our institute was a diameter ≥ 5.0 cm or a growth rate ≥5 mm/year. We estimated operation-free ratios by initial AAA diameter and changes in AAA growth rates. Patients with an initial AAA diameter < 5.0 cm were divided into 2 groups. Patients with AAA that met the criteria for surgery were classified into the expansion group, and those remaining into the non-expansion group. Their AAA growth rates were compared., Results: The group consisted of 124 patients (average age, 73.7±8.6 years (range 54-92)) who had at least 2 recorded AAA measurements. The average follow-up period was 3.0±2.2 years (range 0.3-10.2). There were no cases of rupture during follow-up. Twenty-six patients (21.0%) underwent surgery (open replacement [N.=20]; endovascular abdominal aneurysm repair [N.=6]). The growth rate determined from the initially measured diameter was significantly faster in AAAs measuring 5.0-5.4 cm than in AAAs measuring 4.5-4.9 cm (P=0.01). More than 90% of patients with an initial AAA diameter <5.0 cm were observed conservatively for 2 years or more. However, more than half of the patients with an initial AAA diameter ≥4.0 cm needed surgery within 5 years. The growth rates of AAAs for each size during growth were significantly faster when the AAA diameter was 4.5-4.9 cm than when it was 4.0-4.4 cm (P=0.006), and when the AAA diameter was 5.0-5.4 cm than when it was 4.5-4.9 cm (P = 0.009). The expansion and non-expansion groups consisted of 38 (34.2%) and 73 (75.8%) patients, respectively. The AAA growth rate in the expansion group was significantly faster than that in the non-expansion group (3.4±2.2 mm/year vs. 1.4±1.3 mm/year, P=0.0001)., Conclusion: It may be considered that the appropriate indication for AAA repair is defined by a diameter of 5.0 cm for Japanese patients. Patients with AAA that is growing continuously by ≥3 mm/year and who have low operative risk may undergo surgery even if their AAA is <5.0 cm.

Staged repair of extensive thoracic aortic aneurysms is complicated, with a high incidence of interval rupture between stages. We describe the systematic staged hybrid procedure of a previous endovascular repair of a descending aortic aneurysm and open surgical repair of an aortic arch aneurysm. In the second-stage arch repair, the stent graft was easily retracted and fixed, without dissection, around the aortic arch aneurysm distal side. Extensive thoracic aortic aneurysms were managed without interim rupture or neurologic deficits. This approach avoided the potential for interim rupture because recovery from the first-stage endovascular repair was shorter than that from open repair., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The surgical reconstruction of intrahilar renal artery aneurysms (RAAs) is a difficult surgery because of complex anatomy. We present a case of right intrahilar RAA diagnosed in a 67-year-old man. We performed ex vivo reconstruction using an organ preservation solution to prevent postoperative renal failure. We assessed graft patency and blood perfusion was assessed by laser-assisted indocyanine green angiography using the SPY system after autotransplantation. Postoperative renal insufficiency was not observed. The results demonstrate that ex vivo reconstruction of intrahilar RAAs using an organ preservation solution, and graft patency and blood perfusion evaluation using the SPY system are effective methods for preserving renal function., (Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To minimize surgical invasiveness for extensive aortic aneurysms and expand the indications for thoracic endovascular aortic repair (TEVAR), we evaluated outcomes of hybrid procedures combining conventional surgical aortic repair and TEVAR for thoracic aortic aneurysms., Methods: The following hybrid procedures were performed: second-stage TEVAR after total aortic arch replacement using the elephant trunk as the landing zone in 17 patients; and for multiple aortic aneurysms, vascular graft replacement and TEVAR in 13 patients, vascular graft replacement and TEVAR with bypass in 2 patients, and TEVAR with bypass in 23 patients., Results: There were three (5.3%) hospital deaths, from serious complications including stroke, paraplegia, paraparesis, and aspiration pneumonia; and eight late deaths. There was only one aneurysm-related death, of a patient who underwent emergency surgery for an esophageal fistula resulting from enlargement of a residual false lumen of a thoracoabdominal aorta after second-stage TEVAR., Conclusion: Hybrid procedures minimize surgical invasiveness in thoracic aortic aneurysm repair, but further evaluation of a larger number of patients is necessary.

Aim: To assess the utility of skin perfusion pressure (SPP) measurement in evaluating the outcome of vascular constructions for critical limb ischemia (CLI) patients., Methods: We retrospectively studied 19 lower limbs in 18 patients who underwent arterial reconstruction for CLI from whom SPP measurements had been obtained pre- and postoperatively between 2008 and 2010. Six limbs whose ulcers had healed postoperatively were classified into group H, 7 limbs whose ulcers had not healed into group U, and 6 limbs without ulcers into group N. SPP values were compared among these groups., Results: The preoperative SPP values in all groups were <30 mmHg, without significant differences among the groups. The SPP values in groups H and N significantly improved after operation, and those in group U were significantly lower than those in the other groups., Conclusions: SPP measurement before and after arterial reconstruction is useful to assess improvement in tissue circulation and to predict the likelihood of wound healing. An SPP value ≥30 mmHg was considered necessary for wound healing, supporting the findings of the few reports in the literature on the usefulness of SPP for assessing vascular reconstruction effects on ulcer wound healing.

Purpose: We investigated the surgical results of secondary thoracic endovascular aneurysm repair (TEVAR) using the elephant trunk graft after total aortic arch replacement (TAR) for extensive thoracic aortic lesions., Methods: The subjects comprised 16 patients who underwent TEVAR as a staged procedure following TAR at our institution between 1997 and 2007. Long-term results were retrospectively surveyed (mean observation period 68.4 months). We performed TEVAR with the elephant trunk graft as a proximal landing zone for the descending thoracic repair, the mean duration between TAR and TEVAR was 4.7 weeks for the staged operations and 18.3 months for the nonstaged operations., Results: Early results were good in all cases, with no deaths and no noteworthy complications. For the seven patients without dissection, long-term results were also good. Among the nine patients with dissection, the false lumen in the thoracoabdominal area enlarged in three during follow-up. We performed thoracoabdominal repair in two, but one died of an aneurysm-esophageal fistula. There was only one long-term aneurysm-related death., Conclusion: Second-stage TEVAR using the elephant trunk graft after TAR allows less invasive surgery for extensive aortic lesions and achieves good long-term results. However, enlargement of the false lumen was a long-term concern in patients with aortic dissection, and careful follow-up is essential.

Background: The bioactive lipid lysophosphatidylserine (LPS) is postulated to induce important biological responses and to be produced by phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)). To evaluate the functional roles of LPS in vivo, a facile assay method for PS-PLA(1) has been awaited., Methods: Recombinant human PS-PLA(1) was produced using a baculovirus system, and anti-human PS-PLA(1) monoclonal antibodies were generated. Two clones were then selected for a 2-site immunoassay. The resulting PS-PLA(1) assay reagent was applied to a commercial automated immunoassay analyzer., Results: Satisfactory results were obtained for the within-run and between-run precision, interference, detection limit, and linearity of this PS-PLA(1) assay. The mean+/-SD of the serum PS-PLA(1) antigen concentration in the 191 healthy subjects was 33.8+/-16.6microg/l, and the central 95th percentile reference interval for the serum PS-PLA(1) antigen concentration was 13.8-74.1microg/l. The concentration was significantly (p<0.001) higher among men (13.8-80.6microg/l) than among women (12.1-68.8microg/l). We did not find a correlation between PS-PLA(1) and existing laboratory tests., Conclusions: The present PS-PLA(1) assay method can be applied to clinical laboratory testing, and further studies are warranted to establish its clinical significance., (Copyright 2010 Elsevier B.V. All rights reserved.)

Aortic anomaly in which a right-sided aortic arch associated with Kommerell's diverticulum and aberrant left subclavian artery is rare. The present report describes a patient with type-B aortic dissection accompanying aortic anomalies consisting of right-sided aortic arch and the left common carotid and left subclavian artery arising from Kommerell's diverticulum. As dissecting aortic aneurysm diameter increased rapidly, Single-stage surgical repair of extensive thoracic aorta was performed through median sternotomy and right posterolateral fifth intercostal thoracotomy, yielding favorable results. Our surgical procedures are discussed.

We herein present a 60 years old woman with Takayasu arteritis and an extensive thoracic aortic aneurysm who initially underwent a total aortic arch replacement. Then, in the second stage, thoracic endovascular aortic repair was performed using the elephant trunk graft as the proximal landing zone at four weeks after aortic arch repair. The postoperative course was relatively uncomplicated, but a type II endoleak was noted. Currently, about 5 years postoperatively, the slight type II endoleak from intercostal artery persists, but aneurism dilatation has not been noted, so the patient is being followed up.

Objective: For the early diagnosis and therapy of peripheral thromboembolism (TE) as a complication of abdominal aortic repair (AAR), we developed and evaluated the usefulness of surgical drapes that permit observation of the lower extremities during AAR., Materials and Methods: Between January 2007 and June 2009, the handling, durability, and usefulness of new surgical drapes were evaluated during AAR in 157 patients with abdominal aortic aneurysms and 9 patients with peripheral arterial disease. The drapes are manufactured by Hogy Medical Co. Ltd. and made of a water-repellent, spun lace, non-woven fabric, including a transparent polyethylene film that covers the patients' legs. This transparent film enables inspection and palpation of the lower extremities during surgery for early diagnosis and therapy of peripheral TE., Results: As a peripheral complication, 1 patient had right lower extremity TE. This was diagnosed immediately after anastomosis, thrombectomy was performed, and the remaining clinical course was uneventful. In all patients, the drapes permitted observation of the lower extremities , and the dorsal arteries were palpable. There were no problems with durability., Conclusions: New surgical drapes permit observation of the lower extremities during AAR for early diagnosis and treatment of peripheral TE.

Purpose: We evaluated the operative results of our treatment for multiple aortic aneurysms by means of a hybrid procedure consisting of a combination of conventional surgical maneuvers and simultaneous or sequential endovascular aortic repair (EVAR)., Materials and Methods: From August 1998 to April 2007, a total of 15 patients, 11 men and 4 women, ranging in age from 62 to 78 years, were treated with hybrid procedures for multiple aortic aneurysms. The pathology of these patients were, atherosclerotic aneurysm in 12 patients, atherosclerotic aneurysm associated with chronic dissection in 2 and type III chronic dissection in 1 patient. The distribution of aneurysmal locations were as follows: 5 patients had aneurysms at the arch and descending aorta, 1 had at the arch and thoracoabdominal aorta, 6 at the descending and abdominal aorta. Two patients with chronic dissection had simultaneous abdominal aortic aneurysms. In all except 1 of the 7 patients who had abdominal aortic aneurysm, we performed abdominal aneurysmectomy and EVAR simultaneously. In 7 patients, EVAR was performed sequentially after graft replacement surgery. In 2 patients, EVAR was the initial procedure followed by conventional surgery. The mean interval between first and second stage procedures was approximately 4 months., Results: One patients died of methicillin resistant Staphylococcus aureus pneumonia 3 months after the simultaneous procedure, all others were discharged and survive. In particular, no major EVAR linked complication was observed in the follow-up period (range 3 to 91 months, mean 46 months)., Conclusion: The hybrid procedure for the treatment of multiple aortic aneurysmal disease is less invasive compared to conventional staged surgery and the outcome in terms of mortality and morbidity in hospital as well as long-term follow-up are satisfactory.

Phospholipase A1 (PLA1) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Mammals have several enzymes that exhibit PLA1 activity in vitro. The extracellular PLA1s include phosphatidylserine (PS)-specific PLA1 (PS-PLA1), membrane-associated phosphatidic acid (PA)-selective PLA1s (mPA-PLA1alpha and mPA-PLA1beta), hepatic lipase (HL), endothelial lipase (EL) and pancreatic lipase-related protein 2 (PLRP2), all of which belong to the pancreatic lipase gene family. The former three PLA1s differ from other members in their substrate specificities, structural features and gene organizations, and form a subfamily in the pancreatic lipase gene family. PS-PLA1, mPA-PLA1alpha and mPA-PLA1beta exhibit only PLA1 activity, while HL, EL and PLRP2 show triacylglycerol-hydrolyzing activity in addition to PLA1 activity. The tertiary structures of lipases have two surface loops, the lid and the beta9 loop. The lid and the beta9 loop cover the active site in its closed conformation. An alignment of amino acid sequences of the pancreatic lipase gene family members revealed two molecular characteristics of PLA1s in the two surface loops. First, lipase members exhibiting PLA1 activity (PS-PLA1, mPA-PLA1alpha and mPA-PLA1beta, EL, guinea pig PLRP2 and PLA1 from hornet venom (DolmI)) have short lids. Second, PS-PLA1, mPA-PLA1alpha, mPA-PLA1beta and DolmI, which exhibit only PLA(1) activity, have short beta9 loops. Thus, the two surface loops appear to be involved in the ligand recognition. PS-PLA1 and mPA-PLA1s specifically hydrolyze PS and PA, respectively, producing their corresponding lysophospholipids. Lysophosphatidylserine and lysophosphatidic acid have been defined as lipid mediators with multiple biological functions. Thus, these PLA1s have a role in the production of these lysophospholipid mediators.

Obstruction of the endograft limb by thrombosis has often been reported and may cause fatal complications such as leg necrosis or myonephropathic metabolic syndrome. The purpose of this study was to evaluate endograft antithrombogenicity by indium-111 platelet scintigraphy. Seventeen patients with abdominal aortic aneurysms were treated by endografting. Thirteen patients were treated with conventional open surgery using an artificial graft. The endograft was constructed from a self-expanding Z-shaped stent and woven polyester fabric. Autologous platelets labeled with indium-111 were injected at 2 weeks postoperatively. At 24 hours and 72 hours postinjection, the ratio of scintillation count of the endograft or graft to that of the native artery was calculated to assess platelet deposition. The normalization ratio was calculated as follows: (scintillation count per pixel of endograft or graft/circumference)/(scintillation count per pixel of the native femoral artery). Platelet factor 4 and beta-thromboglobulin were measured to evaluate the systemic platelets activity at 2 weeks postoperatively. There was no significant difference in platelet counts or labeling efficiency between the groups. The ratio was significantly higher in the endografting group than in the open surgery group at 72 hours postinjection (2.5-0.7 vs 3.9-1.1, P<.001). There was no significant difference in platelet factor 4 and beta-thromboglobulin between the groups. Although there was no difference in systemic platelet activity, endografting was associated with lower antithrombogenicity. It remains unclear whether lower antithrombogenicity causes thromboembolism as a complication of the procedure. The authors recommend the administration of antiplatelet drugs to prevent endograft obstruction in patients with very narrow iliac arteries.

Between October 1996 and June 2003, endovascular stent graft repair was performed in 87 patients with descending thoracic aortic aneurysms, graft replacement was performed in 24 patients with thoracoabdominal aortic aneurysms, and endovascular stent graft repair with concomitant surgical bypass of abdominal visceral arteries was performed in 3 patients with thoracoabdominal aortic aneurysms. The retrievable stent graft was inserted and evoked spinal cord potential were monitored in order to predict spinal cord ischemia for stent graft repair. There was no paraplegia or hospital death, although 3 patients had paraparesis in stent graft repair. Two of the 3 patients with paraparesis made a full neurologic recovery. There were no cases of paraplegia or paraparesis in surgical operations with thoracoabdominal aortic aneurysm. The concomitant surgical procedure was a good technique for patients in whom cardiopulmonary bypass could not be used. Our results of stent graft repair and surgical operation for descending thoracic or thoracoabdominal aortic aneurysms were acceptable. The retrievable stent graft was useful for prediction of spinal cord ischemia before endovascular stent graft repair of descending thoracic or thoracoabdominal aortic aneurysm.