Publications by authors named "Chisato Sato"

20 Publications

  • Page 1 of 1

Incomplete Recovery From Takotsubo Syndrome Is a Major Determinant of Cardiovascular Mortality.

Circ J 2021 Apr 6. Epub 2021 Apr 6.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire.

Background: Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P<0.001) and C-reactive protein levels (OR: 1.11; 95% CI: 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001).

Conclusions: This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.
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http://dx.doi.org/10.1253/circj.CJ-20-1116DOI Listing
April 2021

D-Dimers Level as a Possible Marker of Extravascular Fibrinolysis in COVID-19 Patients.

J Clin Med 2020 Dec 24;10(1). Epub 2020 Dec 24.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 67000 Strasbourg, France.

Background And Objective: Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events.

Methods: This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU).

Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 ( = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50-4.86); < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 ( < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27-4.93); = 0.008).

Conclusions: In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
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http://dx.doi.org/10.3390/jcm10010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795726PMC
December 2020

Risk and Severity of COVID-19 and ABO Blood Group in Transcatheter Aortic Valve Patients.

J Clin Med 2020 Nov 22;9(11). Epub 2020 Nov 22.

Division of Cardiovascular Medicine, Strasbourg University Hospital, 67000 Strasbourg, France.

While cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have described its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Numerous observational studies have reported an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection. Our objective was to investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The occurrence and severity (hospitalization and/or death) of COVID-19 and their associations with the ABO blood group served as the main outcome measures. Of the 1125 patients who had undergone TAVR, 403 (36%) died before 1 January 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Of them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariable analysis identified the A blood group (vs. others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio (OR) = 6.32; 95% confidence interval (CI) = 2.11-18.92; = 0.001). The A blood group (vs. others; OR = 8.27; 95% CI = 1.83-37.43, = 0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64-15.27, = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). We conclude that patients who have undergone TAVR frequently have a number of cardiovascular comorbidities that may work to increase the risk of COVID-19. The subgroup with the A blood group was especially prone to developing the disease and showed unfavorable outcomes.
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http://dx.doi.org/10.3390/jcm9113769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700222PMC
November 2020

Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients.

ESC Heart Fail 2021 Feb 18;8(1):259-269. Epub 2020 Nov 18.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France.

Aims: Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS.

Methods And Results: Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty-five patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025).

Conclusions: Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.
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http://dx.doi.org/10.1002/ehf2.12945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835625PMC
February 2021

Clinical features of patients with acute coronary syndrome during the COVID-19 pandemic.

J Thromb Thrombolysis 2020 Nov 16. Epub 2020 Nov 16.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg cedex, France.

Although a reduction in hospital admissions of acute coronary syndromes (ACS) patients has been observed globally during the coronavirus disease 2019 (COVID-19) pandemic, clinical features of those patients have not been fully investigated. The aim of the present analysis is to investigate the incidence, clinical presentation, and outcomes of patients with ACS during the COVID-19 pandemic. We performed a retrospective analysis of consecutive patients who were admitted for ACS at our institution between March 1 and April 20, 2020 and compared with the equivalent period in 2019. Admissions for acute myocardial infarction (AMI) reduced by 39.5% in 2020 compared with the equivalent period in 2019. Owing to the emergency medical services (EMS) of our region, all time components of ST-elevated myocardial infarction care were similar during the COVID-19 outbreak as compared with the previous year's dataset. Among the 106 ACS patients in 2020, 7 patients tested positive for COVID-19. Higher incidence of type 2 myocardial infarction (29% vs. 4%, p = 0.0497) and elevated D-dimer levels (5650 μg/l [interquartile range (IQR) 1905-13,625 μg/l] vs. 400 μg/l [IQR 270-1050 μg/l], p = 0.02) were observed in COVID-19 patients. In sum, a significant reduction in admission for AMI was observed during the COVID-19 pandemic. COVID-19 patients were characterized by elevated D-dimer levels on admission, reflecting enhanced COVID-19 related thrombogenicity. The prehospital evaluation by EMS may have played an important role for the timely revascularization for STEMI patients.
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http://dx.doi.org/10.1007/s11239-020-02340-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668406PMC
November 2020

Role of arthroconidia in biofilm formation by Trichosporon asahii.

Mycoses 2021 Jan 23;64(1):42-47. Epub 2020 Sep 23.

Department of Microbiology, Meiji Pharmaceutical University, Tokyo, Japan.

Background: Trichosporon asahii is the major causative agent of disseminated and deep-seated trichosporonosis. It is capable of forming biofilms on surfaces, leading to medical device-related infection.Trichosporon asahii may be present as yeast form, hyphae and/or arthroconidia; however, the relationship between its biofilm-forming ability and its morphological transition is unclear.

Objectives: We investigated whether the T. asahii morphological transition contributes to its biofilm formation. We also determined the conditions required to induce each of the morphologies.

Methods: Three high- and three low-biofilm-producing strains (HBS and LBS, respectively) were selected using a biofilm formation assay, and the cell surface hydrophobicity of these six strains was measured. For each strain, the morphology was observed and the number of each morphological form (yeast form, hypha and arthroconidium) was counted to calculate the ratio. Finally, the ability of cells each morphological type to adhere to the polystyrene substrate was evaluated.

Results: The HBS exhibited abundant arthroconidia and hyphae; in contrast, the LBS produced mainly hyphae with few or no arthroconidia. The production of hyphae was increased by nitrogen-containing medium, and the production of arthroconidia was increased by nitrogen-deficient medium. Cells incubated under nitrogen-deficient conditions showed higher adherence to a polystyrene surface than those incubated in the presence of nitrogen.

Conclusion: Arthroconidia of T. asahii play a key role in biofilm formation by promoting cellular adhesion.
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http://dx.doi.org/10.1111/myc.13181DOI Listing
January 2021

Staging Severity of COVID-19 according to Hemostatic Abnormalities (CAHA Score).

Thromb Haemost 2020 Dec 30;120(12):1716-1719. Epub 2020 Aug 30.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.

This is the first study to show a stepwise increase in venous thrombotic events according to COVID-19 coagulopathy (COVID-19-associated hemostatic abnormalities [CAHA]) staging and lung injuries assessed by chest computed tomography. Excess mortality and/or transfer to intensive care unit according to CAHA staging.
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http://dx.doi.org/10.1055/s-0040-1715836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869051PMC
December 2020

Paradoxical Increase of Stroke in Patients with Defect of High Molecular Weight Multimers of the von Willebrand Factors following Transcatheter Aortic Valve Replacement.

Thromb Haemost 2020 Sep 29;120(9):1330-1338. Epub 2020 Jul 29.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, Strasbourg, France.

Background:  Stroke is a major cause of disability after transcatheter aortic valve replacement (TAVR) and stroke prediction models and data are crucially needed. Following TAVR, high molecular weight (HMW) multimers defect of von Willebrand factor (VWF) as assessed by closure time of adenosine diphosphate (CT-ADP) value > 180 seconds is an independent predictor of bleeding events. This study sought to identify predictors of ischemic neurological events in patients who underwent TAVR and the specific impact of HMW multimers defect of VWF.

Methods:  Patients were prospectively enrolled between November 2012 and May 2018 at our institution. The CT-ADP, a point-of-care measure of hemostasis, was assessed the day before and 24 hours after the procedures. The rate of ischemic stroke and transient ischemic attack (TIA) was recorded up to 30 days after the procedures.

Results:  Of 565 TAVR patients, ischemic stroke/TIA was observed in 21 (3.7%) patients within 30 days. Ischemic stroke/TIA was associated with major/life-threatening bleeding complications (MLBCs) (9 [43%] vs. 88 [16%],  = 0.002) and postprocedure CT-ADP > 180 seconds (10 [48%] vs. 116 [21%],  = 0.01). By multivariate analysis, MLBCs (odds ratio [OR]: 3.58; 95% confidence interval [CI]: 1.45-8.84;  = 0.006) and postprocedure CT-ADP > 180 seconds (OR: 3.38; 95% CI: 1.38-8.25;  = 0.008) were evidenced as independent predictors of ischemic stroke/TIA.

Conclusion:  MLBCs and CT-ADP > 180 seconds were identified as predictors for ischemic stroke or TIA. The present study suggests that the defects of HMW multimers of the VWFs may contribute not only to bleeding events but also to thrombotic events.
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http://dx.doi.org/10.1055/s-0040-1713424DOI Listing
September 2020

Venous thromboembolism in non-critically ill patients with COVID-19 infection.

Thromb Res 2020 09 17;193:166-169. Epub 2020 Jul 17.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France; INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367026PMC
September 2020

Influence of sex on the incidence of potential coronary artery disease and long-term outcomes in asymptomatic patients with diabetes mellitus.

Int J Cardiol Heart Vasc 2020 Apr 26;27:100504. Epub 2020 Mar 26.

Division of Cardiology, Cardiovascular Center, Showa University Koto-Toyosu Hospital, 5-1-38, Toyosu, Koto-ku, Tokyo, Japan.

Background: Diabetic patients often have coronary artery disease (CAD) without symptoms. It is known that females tend to have silent or less chest pain and worse prognoses when they develop acute coronary syndrome. Thus, sex differences may impact long-term outcomes in diabetes mellitus (DM) patients with silent myocardial ischemia (SMI). The present study aimed to assess the influence of sex on long-term outcomes in DM patients with SMI.

Methods: A total of 461 consecutive asymptomatic and self-sufficient DM patients seen at our hospital from 2011 to 2017 were prospectively reviewed. Patients underwent an ergometer exercise test. When the exercise test was positive or the patient could not achieve 90% of their target heart rate, coronary angiography was performed. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), including death, non-fatal myocardial infarction, and stroke.

Results: SMI was diagnosed in 81 patients. The median follow-up duration from diagnosis was 35 (15-57) months. The incidence of SMI was similar in females and males [34/170 (20%) vs. 47/291 (16.2%),  = 0.36]. Enrolled patients were divided into four groups according to sex and the presence/absence of SMI. Female patients with SMI showed worse clinical outcomes. After adjustment for age and coronary risk factors, female SMI was independently associated with MACCEs [hazard ratio 2.59, 95% confidence interval 1.07-5.68,  = 0.024], while male SMI was not.

Conclusions: Female SMI was associated with worse long-term outcomes in DM patients. Early diagnosis of potential SMI and appropriate care are required in female DM patients. (UMIN000038340).
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http://dx.doi.org/10.1016/j.ijcha.2020.100504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109624PMC
April 2020

N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, a zinc chelator, inhibits biofilm and hyphal formation in Trichosporon asahii.

BMC Res Notes 2020 Mar 10;13(1):142. Epub 2020 Mar 10.

Department of Microbiology, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan.

Objective: Trichosporon asahii is the major causative fungus of disseminated or deep-seated trichosporonosis and forms a biofilm on medical devices. Biofilm formation leads to antifungal drug resistance, so biofilm-related infections are relatively difficult to treat and infected devices often require surgical removal. Therefore, prevention of biofilm formation is important in clinical settings. In this study, to identify metal cations that affect biofilm formation, we evaluated the effects of cation chelators on biofilm formation in T. asahii.

Results: We evaluated the effect of cation chelators on biofilm formation, since microorganisms must assimilate essential nutrients from their hosts to form and maintain biofilms. The inhibition by N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) was greater than those by other cation chelators, such as deferoxamine, triethylenetetramine, and ethylenediaminetetraacetic acid. The inhibitory effect of TPEN was suppressed by the addition of zinc. TPEN also inhibited T. asahii hyphal formation, which is related to biofilm formation, and the inhibition was suppressed by the addition of zinc. These results suggest that zinc is essential for biofilm formation and hyphal formation. Thus, zinc chelators have the potential to be developed into a new treatment for biofilm-related infection caused by T. asahii.
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http://dx.doi.org/10.1186/s13104-020-04990-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063706PMC
March 2020

Systemic Inflammatory Response Syndrome Is a Major Determinant of Cardiovascular Outcome in Takotsubo Syndrome.

Circ J 2020 03 7;84(4):592-600. Epub 2020 Mar 7.

Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg.

Background: Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS.Methods and Results:The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death.

Conclusions: SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.
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http://dx.doi.org/10.1253/circj.CJ-19-1088DOI Listing
March 2020

Atrial Fibrillation Progression Is Associated with Cell Senescence Burden as Determined by p53 and p16 Expression.

J Clin Med 2019 Dec 23;9(1). Epub 2019 Dec 23.

INSERM UMR 1260-Regenerative Nanomedecine, FMTS, Université de Strasbourg-Faculté de Pharmacie, 67401 Illkirch-Graffenstaden, France.

Background: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear.

Aims: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR).

Methods: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis.

Results: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.
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http://dx.doi.org/10.3390/jcm9010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019631PMC
December 2019

Worsening renal failure due to renal steal by aortoiliac bypass.

BMJ Case Rep 2019 Mar 31;12(3). Epub 2019 Mar 31.

Department of Cardiovascular Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan.

Aortoiliac bypass surgery is the gold standard strategy for removing persistent ischaemia resulting from bilateral aortoiliac occlusive disease, a condition known as Leriche syndrome. However, the impact of aortoiliac bypass surgery on the blood flow of the renal artery is not fully understood. Here, we report a case of worsening renal failure caused by renal steal immediately after aortoiliac bypass for Leriche syndrome. The revascularisation of bilateral renal arteries dramatically improved the patient's renal function and allowed us to discontinue both haemodialysis and diuretics. This case demonstrates that in rare instances, haemodynamic change induced by aortoiliac bypass surgery affects the arteries feeding other organs. Careful preoperative evaluation for the corresponding branches of the aorta is indispensable. Optimal revascularisation should be performed to avoid serious complications after aortoiliac bypass if the patient is at risk of developing critical ischaemia.
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http://dx.doi.org/10.1136/bcr-2018-227775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453277PMC
March 2019

Clinical impact of undersized- versus oversized-stenting approaches in ST-elevation myocardial infarction.

Cardiovasc Revasc Med 2016 Sep 15;17(6):362-8. Epub 2016 Apr 15.

Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba district, Yokohama city, Kanagawa prefecture, Japan, 227-8501.

Background: Primary percutaneous coronary intervention (PCI) is the standard treatment in patients with ST-elevation myocardial infarction (STEMI). However, some patients still develop ST re-elevation during PCI, resulting in further myocardial damage and a poor outcome. An undersized-stenting approach may prevent ST re-elevation. We aimed to determine the association between final stent area and ST re-elevation during primary PCI for STEMI.

Methods: Overall, 102 consecutive STEMI patients who underwent primary PCI under integrated backscatter intravascular ultrasound guidance were enrolled. The stent-reference (SR) ratio was defined as the stent cross-sectional area (CSA) divided by the average CSA of the 5-mm proximal and distal reference lumens. The patients were divided into two groups according to the SR ratio: undersize group (SR<1.0, n=62) and oversize group (SR≥1.0, n=40). The incidences of ST re-elevation and total ST resolution (STR) were compared.

Results: The oversize group showed a higher incidence of ST re-elevation (32.5 vs. 9.7%, p=0.004) and a lower total STR (22.4±62.7 vs. 43.4±38.6%, p=0.04). After adjustment, the oversized-stenting approach was independently associated with ST re-elevation [odds ratio: 3.74, 95% confidence interval (CI) 1.27-12.1, p=0.02]. The peak creatine kinase-MB level was higher in the oversize group (341±259 vs. 242±208IU/l, p=0.04). The incidences of stent thrombosis and restenosis were similar between the two groups.

Conclusions: An oversized-stenting approach in patients with STEMI was associated with a higher incidence of ST re-elevation and a lower total STR, resulting in increased myocardial damage.
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http://dx.doi.org/10.1016/j.carrev.2016.04.004DOI Listing
September 2016

Priming with erythropoietin enhances cell survival and angiogenic effect of mesenchymal stem cell implantation in rat limb ischemia.

Regen Ther 2016 Jun 13;4:1-8. Epub 2016 Feb 13.

Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan.

Introduction: Bone marrow mesenchymal stem cells (BMMSCs) ameliorate tissue damage after ischemic injury. Erythropoietin (Epo) has pleiotropic effects in addition to hematopoietic activity. The aim of this study was to investigate whether Epo enhanced cell survival and angiogenic effect of BMMSC implantation in rat limb ischemia model.

Methods And Results: MSCs were isolated from BM in GFP-transgenic rats. In a culture study, Epo promoted BMMSC proliferation in normoxia and enhanced cell survival under the culture condition mimicking ischemia (1% oxygen and nutrient deprivation). BMMSCs with and without 48 h of pretreatment by Epo (80 IU/ml) were locally administered to rat hindlimb ischemia models . At 3 days after implantation, BMMSC engraftment in the perivascular area of the injured muscle was significantly higher in the cells preconditioned with Epo than in the cells without preconditioning. Stromal derived factor-1α and fibroblast growth factor-2 expressions were detected in the engrafted BMMSCs. At 14 days after implantation, the Epo-preconditioned BMMSCs significantly promoted blood perfusion and capillary growth compared to the controls in laser Doppler and histological studies. In addition to promoting neovascularization, the Epo-preconditioned BMMSCs significantly inhibited macrophage infiltration in the perivascular area.

Conclusion: Epo elicited pro-survival potential in the BMMSCs. Pharmacological cell modification with Epo before implantation may become a feasible and promising strategy for improving current therapeutic angiogenesis with BMMSCs.
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http://dx.doi.org/10.1016/j.reth.2016.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581814PMC
June 2016

Fibroblast growth factor-23 induces cellular senescence in human mesenchymal stem cells from skeletal muscle.

Biochem Biophys Res Commun 2016 Feb 18;470(3):657-662. Epub 2016 Jan 18.

Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan.

Although muscle wasting and/or degeneration are prevalent in patients with chronic kidney disease, it remains unknown whether FGF-23 influences muscle homeostasis and regeneration. Mesenchymal stem cells (MSCs) in skeletal muscle are distinct from satellite cells and have a known association with muscle degeneration. In this study we sought to investigate the effects of FGF-23 on MSCs isolated from human skeletal muscle in vitro. The MSCs expressed FGF receptors (1 through 4) and angiotensin-II type 1 receptor, but no traces of the Klotho gene were detected. MSCs and satellite cells were treated with FGF-23 and angiotensin-II for 48 h. Treatment with FGF-23 significantly decreased the number of MSCs compared to controls, while treatment with angiotensin-II did not. FGF-23 and angiotensin-II both left the cell counts of the satellite cells unchanged. The FGF-23-treated MSCs exhibited the senescent phenotype, as judged by senescence-associated β-galactosidase assay, cell morphology, and increased expression of p53 and p21 in western blot analysis. FGF-23 also significantly altered the gene expression of oxidative stress regulators in the cells. In conclusion, FGF-23 induced premature senescence in MSCs from skeletal muscle via the p53/p21/oxidative-stress pathway. The interaction between the MSCs and FGF-23 may play a key role in the impaired muscle reparative mechanisms of chronic kidney disease.
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http://dx.doi.org/10.1016/j.bbrc.2016.01.086DOI Listing
February 2016

Natural course of isolated spontaneous coronary artery dissection in Marfan syndrome.

Int J Cardiol 2014 Nov 28;177(1):20-2. Epub 2014 Sep 28.

Division of Cardiology, Showa University Fujigaoka Hospital, 1-30, Fujigaoka, Aoba-ku, Yokohama, Japan.

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http://dx.doi.org/10.1016/j.ijcard.2014.09.061DOI Listing
November 2014

Syntheses and pharmacokinetic studies of prodrug esters for the development of oral carbapenem, L-084.

J Antibiot (Tokyo) 2006 Apr;59(4):241-7

Medical Research Laboratories, Wyeth K.K., 1-6-34 Kashiwa-cho, Shiki-shi, Saitama 353-8511, Japan.

We discovered an orally active carbapenem, L-084, through pharmacokinetic studies on various prodrug esters of (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-l-methyl-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-em-3-carboxylic acid (LJC11,036). L-084 showed a strong antimicrobial activity against Gram-positive and Gram-negative bacteria and exhibited the highest intestinal absorption among synthesized prodrugs of LJC11,036.
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http://dx.doi.org/10.1038/ja.2006.34DOI Listing
April 2006

A novel, mild, and facile method to prepare 6-methylidene penem derivatives.

J Org Chem 2004 Sep;69(18):5850-60

Medical Research Laboratories, Wyeth Lederle Japan, Ltd., 1-6-34 Kashiwa-cho, Shiki-shi, Saitama 353-8511, Japan.

A novel and mild method was established to synthesize 6-methylidene penem compounds. This method entails a MgBr(2)/Et(3)N-promoted aldol-type condensation on 6-bromopenem 12 with an appropriately substituted aldehyde to yield the intermediate acetylated bromohydrin, which was smoothly converted to the final product with simultaneous deprotection of C3 carboxylic acid ester using activated zinc dust and phosphate buffer at pH 6.5. This process provides a useful variation of C-C bond formation method for penem derivatives and also serves as a practical synthetic method to prepare 6-exomethylenepenem derivatives without racemization at the C5 position.
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http://dx.doi.org/10.1021/jo049880gDOI Listing
September 2004