Publications by authors named "Kazuaki Tanabe"

232 Publications

Assessment of organ congestion in patients with heart failure by ultrasonography.

J Echocardiogr 2021 Jul 27. Epub 2021 Jul 27.

Division of Cardiology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, 693-8501, Japan.

In recent years, there has been a growing interest in assessing congestion of organs (e.g., liver, kidneys, lungs, intestines) in patients with heart failure (HF). HF involves an increased risk of mortality, thereby making it important to evaluate organ congestion. Ultrasonography is a useful tool for noninvasive and repeatable evaluation of patients with HF. Noninvasive evaluation of organ congestion can also be used to assess hemodynamics. It may further be useful for elucidating organ cross-talk in patients with HF. This review discusses the clinical implications of evaluating organ congestion by ultrasonography.
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http://dx.doi.org/10.1007/s12574-021-00541-wDOI Listing
July 2021

Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance.

Gastric Cancer 2021 Jul 16. Epub 2021 Jul 16.

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish.

Methods: In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments.

Results: We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth.

Conclusions: Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases.
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http://dx.doi.org/10.1007/s10120-021-01206-4DOI Listing
July 2021

Accelerated Idioventricular Rhythm Following Transcatheter Self-Expandable Aortic Valve Implantation.

Circ Rep 2021 Jul 17;3(7):421-422. Epub 2021 Jun 17.

Division of Cardiology, Shimane University Faculty of Medicine Izumo Japan.

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http://dx.doi.org/10.1253/circrep.CR-21-0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258187PMC
July 2021

Therapeutic effects of sleeve gastrectomy for non-alcoholic steatohepatitis estimated by paired liver biopsy in morbidly obese Japanese patients.

Medicine (Baltimore) 2021 Jul;100(26):e26436

Department of Gastroenterology and Metabolism.

Abstract: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG.
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http://dx.doi.org/10.1097/MD.0000000000026436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257835PMC
July 2021

A case of Wolff-Parkinson-White syndrome in which two-dimensional speckle-tracking echocardiography was useful for identifying the location of the accessory atrioventricular pathway.

Eur Heart J Case Rep 2021 Mar 4;5(3):ytab078. Epub 2021 Mar 4.

Division of Cardiology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan.

Background: In Wolff-Parkinson-White (WPW) syndrome, accessory atrioventricular pathways (AP) result in abnormal pre-excitation around the atrioventricular annuli and produce a dyssynchronous contraction of cardiac chambers. Identification of the AP affects the outcome of catheter ablation.

Case Summary: We report a case of WPW syndrome and paroxysmal atrial fibrillation in a 65-year-old man. Wolff-Parkinson-White syndrome Type B was suspected from lead V1, but when two-dimensional speckle-tracking echocardiography (2D-STE) was performed, a decrease in regional strain was observed in the anterior basal wall of the left ventricle. We identified the earliest site of atrioventricular conduction, and improvement in the regional strain at the site of ablation was observed after successful AP ablation.

Discussion: Various echocardiographic techniques have been investigated as non-invasive alternatives for AP localization. Longitudinal 2D-STE accurately identified contractile abnormalities associated with the AP, allowing us to non-invasively estimate the localization of the AP in WPW syndrome.
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http://dx.doi.org/10.1093/ehjcr/ytab078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186928PMC
March 2021

Hydroxyzine-induced Torsade de Pointes in a Patient with Complete Atrioventricular Block.

Intern Med 2021 Apr 26. Epub 2021 Apr 26.

Division of Cardiology, Shimane University Faculty of Medicine, Japan.

An 82-year-old woman was admitted to our hospital because of dyspnea and bradycardia during exertion. Electrocardiography revealed complete atrioventricular block. During pacemaker implantation, a small dose (12.5 mg) of hydroxyzine was injected for sedation, and torsade de pointes (Tdp) occurred. The QT interval was prolonged after administration of hydroxyzine, and Tdp was observed after the R on T phenomenon occurred, indicating that hydroxyzine was capable of prolonging the QT interval and causing Tdp. Therefore, we must be cautious when administering hydroxyzine for sedation during surgery, especially in patients with bradycardia.
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http://dx.doi.org/10.2169/internalmedicine.7382-21DOI Listing
April 2021

Association Between Atrial High-Rate Episodes and Ischemic/Major Bleeding Events in Patients With a Cardiac Implantable Electronic Device - A 10-Year, Single-Center Historical Cohort Study.

Circ J 2021 Jul 16;85(8):1329-1337. Epub 2021 Apr 16.

Division of Cardiology, Shimane Prefectural Central Hospital.

Background: An association between atrial high-rate episode (AHRE) and stroke has been reported, although data for the Asian population are limited. This study aimed to investigate the role of AHRE in ischemic and major bleeding events in patients who underwent a cardiac implantable electronic device (CIED) procedure.Methods and Results:This single-center historical cohort study included 710 patients (age: 78±11 years, 374 women) who underwent a CIED-related procedure between October 2009 and September 2019 at Shimane Prefectural Central Hospital (median follow-up period: 4.5 [2.5, 7] years, 3439 person-years). Based on the maximum AHRE burden, patients were divided into: (1) <6 min; (2) ≥6 min to 24-h; and (3) ≥24-h groups. The cumulative incidence of ischemic (ischemic stroke, systemic embolism, and transient ischemic attack) and major bleeding (≥3 Bleeding Academic Research Consortium bleeding criteria) events after the procedure were compared. Uni- and multivariate analyses were performed to identify factors associated with these events. The incidence of both events increased with the rising AHRE burden, being significantly higher in the ≥24-h group than in the <6 min group. Multivariate analysis found age ≥85 years to be the only independent factor associated with both events.

Conclusions: Longer AHRE duration is associated with a high number of major bleeding and ischemic events. Monitoring these bleeding risks is mandatory when clinicians are considering anticoagulation therapy for such patients.
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http://dx.doi.org/10.1253/circj.CJ-20-1269DOI Listing
July 2021

String-Like Structure in the Left Atrium.

Circ Rep 2021 Mar 23;3(4):256-257. Epub 2021 Mar 23.

Division of Cardiology, Shimane University Faculty of Medicine Izumo Japan.

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http://dx.doi.org/10.1253/circrep.CR-21-0009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024010PMC
March 2021

Schlafen 11 predicts response to platinum-based chemotherapy in gastric cancers.

Br J Cancer 2021 Jul 30;125(1):65-77. Epub 2021 Mar 30.

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Background: Although unresectable or recurrent gastric cancers (GC) are frequently treated with platinum-based chemotherapy, response to treatment remains unpredictable. Because Schlafen 11 (SLFN11) is recently identified as a critical determinant of platinum sensitivity, we investigated the potential clinical utility of SLFN11 in the treatment of GC.

Methods: We analysed the correlation between SLFN11 expression and overall survival in 169 GC patients by our established immunohistochemical approach. The impact of SLFN11 expression on the response to platinum and transition of SLFN11 expression upon long-term treatment with platinum were examined using GC cell lines and organoids.

Results: GC patients with high-SLFN11 expression exhibited significantly better survival than those with low-SLFN11 expression, and the significance increased when we selected patients treated with platinum-based chemotherapy. Knockout of SLFN11 and reactivation of SLFN11 in GC cells conferred resistance and sensitivity to platinum, respectively. In GC cells and organoids, long-term treatment with oxaliplatin suppressed SLFN11 expression while imparting drug resistance. The acquired resistance to oxaliplatin was reversed by reactivation of SLFN11 with epigenetic modifying drugs.

Conclusions: This is the first report revealing definitive clinical implications of SLFN11 in the treatment of GC patients and providing novel strategies for the drug selection based on SLFN11 expression.
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http://dx.doi.org/10.1038/s41416-021-01364-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257722PMC
July 2021

Zebra Body Formation Due to Drug-Induced Phospholipidosis Observed on Electron Micrographs.

Circ Rep 2021 Jan 13;3(2):110-111. Epub 2021 Jan 13.

Division of Cardiology, Shimane University Faculty of Medicine Izumo Japan.

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http://dx.doi.org/10.1253/circrep.CR-20-0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939952PMC
January 2021

Incidence and Demographic Trends for Acute Coronary Syndrome in a Non-Epidemic Area During the Coronavirus Disease Pandemic in Japan - A 2-Institutional Observational Study.

Circ Rep 2021 Jan 20;3(2):95-99. Epub 2021 Jan 20.

Division of Cardiology, Shimane Prefectural Central Hospital Izumo Japan.

We investigated the incidence of acute coronary syndrome (ACS) in a non-epidemic area of coronavirus disease-2019 (COVID-19) in Japan. This observational study included consecutive patients admitted for ACS at 2 tertiary hospitals in Izumo City during the pandemic in Japan (n=42, March-July 2020). Although the monthly ACS incidence was comparable, the proportions of delayed admissions and high Killip class (III/IV) were significantly higher in this population than in historical cohorts (n=197, 2015-2019). Our findings stress the importance of encouraging patients with ACS-related symptoms to visit medical services promptly, especially in non-epidemic areas.
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http://dx.doi.org/10.1253/circrep.CR-20-0141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939951PMC
January 2021

Recurrent Granulocyte Colony-Stimulating Factor-Induced Aortitis After Pegfilgrastim Administration.

Circ Rep 2020 Oct 27;2(12):764-765. Epub 2020 Oct 27.

Division of Cardiology, Shimane University Faculty of Medicine Izumo Japan.

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http://dx.doi.org/10.1253/circrep.CR-20-0092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937525PMC
October 2020

Development of Alveolar Hemorrhage in a Patient with Acute Myocardial Infarction Complicated with Essential Thrombocythemia.

Am J Case Rep 2021 Feb 9;22:e928409. Epub 2021 Feb 9.

Division of Cardiology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.

BACKGROUND Essential thrombocythemia (ET) is a risk factor both for bleeding caused by abnormal platelet function and for thrombus formation caused by excessive platelet proliferation. We present a rare case of alveolar hemorrhage after dual antiplatelet therapy (DAPT), a serious bleeding complication of antithrombotic therapy, in a patient with an acute myocardial infarction complicated by ET. CASE REPORT A 75-year-old man was treated for ET. He experienced an acute myocardial infarction, and an emergent percutaneous coronary intervention was subsequently performed. DAPT was started just before stent implantation. Because a left ventricular thrombus was suspected in spite of DAPT, anticoagulant therapy with heparin was added. On day 7, a large amount of hemoptysis was observed, and alveolar hemorrhage was diagnosed. Although the antithrombotic treatment was de-escalated from DAPT to single antiplatelet therapy, no stent thrombosis or recurrence of alveolar hemorrhage was observed. CONCLUSIONS In ET patients, reduced platelet function due to thrombocytosis and strong antithrombotic therapy may cause an excessive bleeding risk. Switching from DAPT to antiplatelet monotherapy at the early stage of stent implantation is a treatment option in situations in which excessive bleeding risk is a concern.
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http://dx.doi.org/10.12659/AJCR.928409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883940PMC
February 2021

Clinical effectiveness and adverse events associated with tolvaptan in patients above 90 years of age with acute decompensated heart failure.

Heart Vessels 2021 Jun 2;36(6):836-843. Epub 2021 Feb 2.

Division of Cardiology, Shimane University Faculty of Medicine, Izumo, 693-8501, Japan.

With the aging society, the number of very-elderly (VE) patients with acute decompensated heart failure (ADHF) is increasing. Although tolvaptan is recommended for patients with ADHF in whom conventional diuretic therapy is ineffective, few reports exist on VE patients over 90 years of age. Therefore, we aimed to evaluate the clinical effectiveness and adverse events associated with tolvaptan in VE patients with ADHF. From January 2011 to December 2018, we retrospectively studied 180 patients with ADHF who were first administered tolvaptan during hospitalization. Patients were divided into two groups, namely, VE patients who were ≥ 90 years of age (n = 32) and not-VE patients (NVE) who were < 90 years of age (n = 148). The primary effective endpoints were the total urine volume and change in body weight. The safety endpoints evaluated were the incidence of hypernatremia (≥ 150 mEq/L) and worsening renal function (WRF) at any time during hospitalization. The median [interquartile range] patient age was 93 [91-94] years in the VE group and 80 [69-85] years in the NVE group. The mean dose of tolvaptan for the first week of administration was similar between groups (7.9 ± 5.0 mg, VE group; 7.3 ± 3.7 mg, NVE group; p = 0.52). There were no significant differences between the two groups in the total urine volume at 24 h (1901 ± 666 mL, VE group; 2101 ± 1167 mL, NVE group; p = 0.33) and that at 48 h (3707 ± 1274 mL, VE group; 4195 ± 1990 mL, NVE group; p = 0.19) and in the mean change in body weight (- 2.5 ± 2.0 kg, VE group; -2.7 ± 2.4 kg, NVE group; p = 0.70). The median duration of hospitalization was 24 [20-9] and 31 [20-42] days in the VE and NVE groups, respectively (p = 0.67). The incidence of hypernatremia (6.3% (2/32), VE group; 3.4% (5/148), NVE group; p = 0.61) and WRF (25.0% (8/32) VE group; 19.6% (29/148), NVE group; p = 0.31) was similar between the groups. In conclusion, tolvaptan has similar clinical effectiveness in increasing urine volume and decreasing body weight, without increased adverse events, in VE patients with ADHF who were ≥ 90 years of age compared to NVE patients with ADHF.
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http://dx.doi.org/10.1007/s00380-020-01753-3DOI Listing
June 2021

The Effectiveness of Target Low-Density Lipoprotein Cholesterol Achieved with Strict Management in Secondary Prevention of Long-Term Coronary Events in Japanese Patients.

Acta Cardiol Sin 2021 Jan;37(1):65-73

Division of Cardiology, Shimane University Faculty of Medicine, Izumo, Japan.

Background: In the secondary prevention of long-term coronary events, a target value of low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL is recommended as standard management in Japanese guidelines. However, the effectiveness of strict management on lowering LDL-C remains unclear.

Objectives: To clarify whether strict management of LDL-C < 70 mg/dL is more effective in preventing long-term coronary event recurrence than standard management.

Methods: We retrospectively investigated 344 patients with previous percutaneous coronary interventions who underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early restenosis period from January 2007 to August 2019. Patients were stratified into three groups according to achieved LDL-C value; LDL-C < 70 mg/dL (n = 53), 70 to < 100 mg/dL (n = 130), and ≥ 100 mg/dL (n = 161). Endpoints were acute coronary syndrome (recurrent-ACS) and late coronary revascularization.

Results: After follow-up (median 6.0 years), 200 patients (58%) underwent late coronary revascularization, including 94 recurrent-ACS. The incidence of recurrent-ACS was significantly lower in the patients who achieved LDL-C < 70 mg/dL than in those with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.009 and p = 0.001, respectively). There was no significant difference between the patients with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.140). There was also no significant difference in late revascularization between the patients with LDL-C < 70 mg/dL and LDL-C 70 to < 100 mg/dL. In patients with LDL-C < 100 mg/dL (n = 183), LDL-C [hazard ratio (HR) 1.035, p = 0.007] and HbA1c (HR 1.338, p = 0.001) were independently associated with recurrent-ACS.

Conclusions: In Japanese patients, LDL-C was a residual risk for recurrent-ACS even after recommended standard LDL-C lowering management target values had been achieved.
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http://dx.doi.org/10.6515/ACS.202101_37(1).20200716ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814327PMC
January 2021

Trends Over Time in the Incidences of ST-Segment Elevation Myocardial Infarction and Non-ST-Segment Elevation Myocardial Infarction During the Past Decade in a Rural Japanese High-Aged Population.

Circ J 2021 01 13;85(2):175-184. Epub 2021 Jan 13.

Division of Cardiology, Shimane Prefectural Central Hospital.

Background: In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated.Methods and Results:This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use.

Conclusions: This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.
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http://dx.doi.org/10.1253/circj.CJ-20-0955DOI Listing
January 2021

Tetany Exacerbating Heart Failure: A Case Report.

Cureus 2021 Jan 4;13(1):e12467. Epub 2021 Jan 4.

Cardiology, Shimane University Faculty of Medicine, Izumo, JPN.

Tetany is characterized by numbness and stiffness in the hands and feet caused by hypocalcemia, hypomagnesemia, and hyperventilatory alkalosis, primarily at peripheral neuromuscular junctions. Although hypocalcemia is common in critically ill patients, its diagnosis of hypocalcemia is complicated and sometimes overlooked. We encountered an 82-year-old woman with tetany that exacerbated heart failure. Pain and respiratory failure due to tetany are conditions that can lead to exacerbation of heart failure. Chronic renal failure is frequently associated with chronic heart failure, and regular follow-up of calcium, phosphorus, and magnesium levels is necessary for such patients.
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http://dx.doi.org/10.7759/cureus.12467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785505PMC
January 2021

Iatrogenic hepatic granuloma (suspected liver metastatic lesion on imaging) caused by liver retraction during laparoscopic gastrectomy: A case report.

Clin Case Rep 2020 Dec 15;8(12):2353-2357. Epub 2020 Jul 15.

Department of Gastroenterological and Transplant Surgery Applied Life Sciences Institute of Biomedical and Health Sciences Hiroshima University Hiroshima Japan.

There are no previous reports of hepatic granuloma secondary to intraoperative liver retraction. Using softer hepatic retraction instruments and keeping hepatic retraction time to a minimum are vital in preventing postoperative liver damage.
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http://dx.doi.org/10.1002/ccr3.3100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752566PMC
December 2020

Branching form of celiac artery to be aware of in laparoscopic surgery: A case report using MDCT angiography.

Radiol Case Rep 2021 Mar 17;16(3):476-479. Epub 2020 Dec 17.

Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

The anomalies of the celiac artery have been reported and reviewed in literature. Hence, it is not uncommon to clinically encounter its various types. This report presents the case of a 76-year-old male who underwent laparoscopic distal gastrectomy. Preoperative abdominal contrast-enhanced computed tomography showed an anomaly of the celiac artery, which was extremely rare, with various other anomalies of the artery.
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http://dx.doi.org/10.1016/j.radcr.2020.12.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753074PMC
March 2021

Delirium is associated with high mortality in older adult patients with acute decompensated heart failure.

BMC Geriatr 2020 12 3;20(1):524. Epub 2020 Dec 3.

Department of Cardiology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.

Background: Delirium is associated with high mortality after cardiac surgery. However, evidence on the epidemiology of delirium in patients with acute decompensated heart failure (ADHF) is limited. This study aimed to assess the incidence and prognostic impact of delirium in patients with ADHF.

Methods: This single-center prospective observational study enrolled 132 consecutive patients with ADHF. We utilized the Diagnostic and Statistical Manual of Mental Disorders, fifth edition and classified the patients into two groups according to the presence or absence of delirium. The primary endpoint was 90-day all-cause mortality. The prognostic impact and risk factors of delirium were evaluated using multivariable Cox and logistic regression analyses, respectively.

Results: The median patient age was 83 (interquartile range, 75-87) years. Approximately 51.5% were men. Delirium occurred in 36 (27.3%) patients, and hyperactive delirium was the most frequent type (86.1%). The 90-day all-cause mortality was higher in the patients with delirium than in those without (21.6% versus 3.9%, log-rank p = 0.002). Delirium was associated with higher mortality with an adjusted hazard ratio of 6.8 (95% confidence interval, 1.1-42.6, p = 0.042). The risk factors associated with delirium included advanced age, male sex, higher clinical frailty scale score, and dementia.

Conclusions: Delirium was associated with a higher 90-day all-cause mortality in the older adult patients with ADHF. Hyperactive delirium was the most common subtype.
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http://dx.doi.org/10.1186/s12877-020-01928-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713169PMC
December 2020

A Remarkable Elevation in the Procalcitonin Levels Due to Diabetic Ketoacidosis in a Hemodialysis Patient.

Intern Med 2021 Apr 23;60(8):1231-1235. Epub 2020 Nov 23.

Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan.

Procalcitonin (PCT), a marker of the inflammatory response during infections, can be elevated by diabetic ketoacidosis (DKA). A male patient in his 50s with diabetic nephropathy on hemodialysis presented with vomiting and a reduced level of consciousness and was diagnosed with DKA. His PCT level was markedly elevated, but bacterial cultures (blood, urine, and stool) were negative. The PCT level decreased after DKA improvement. In this patient, DKA probably enhanced the PCT levels. As DKA can increase the PCT levels, an elevation of the PCT levels in DKA patients may not be indicative of infectious diseases, and non-infectious causes of DKA should therefore be considered.
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http://dx.doi.org/10.2169/internalmedicine.5841-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112968PMC
April 2021

Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell.

Oncogene 2020 12 12;39(50):7265-7278. Epub 2020 Oct 12.

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

5-FU is one of the key drugs in the treatment of gastric cancer (GC). Much evidence has shown that cancer stem cells (CSCs) play a key role in the acquisition of drug resistance. The organoid is a novel 3D cell culture system technology that sustains stem-cell-driven formation of near-physiological, self-renewing tissues using specific niche factors in a dish. In this study, we established GC organoids (GCOs) and gradually treated them with higher concentrations of 5-FU. We successfully harvested four 5-FU-resistant GCOs, which were supported by significant changes in the expression of molecules related to 5-FU metabolism. We then performed microarray analysis using three normal gastric organoids and three pairs of 5-FU-resistant and parental GCOs. Through the comparison of expression profiles and further validation, we chose KHDRBS3 as a target gene. We found KHDRBS3 to be an independent prognostic factor in GC patients, especially in GC patients treated with 5-FU chemotherapy. We also determined that KHDRBS3 might play an important role in the acquisition of stem cell-like features, such as multi-drug resistance and organoid formation, by regulating CD44 variant expression. We found KHDRBS3, which is thought to play an important role in the acquisition of characteristics of CSCs in GC, to be a promising candidate marker for predicting therapeutic effect and prognosis in GC patients.
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http://dx.doi.org/10.1038/s41388-020-01492-9DOI Listing
December 2020

Asymptomatic Immune Checkpoint Inhibitor-associated Myocarditis.

Intern Med 2021 Feb 7;60(4):569-573. Epub 2020 Oct 7.

Division of Cardiology, Shimane University Faculty of Medicine, Japan.

We herein report the case of a 75-year-old man with asymptomatic immune checkpoint inhibitor (ICI)-associated myocarditis diagnosed on the basis of elevated levels of creatine kinase (CK), CK-myocardial band and troponin I (TNI). He was suspected of being complicated with myasthenia gravis (MG). High-dose prednisolone (PSL) is associated with a risk of MG exacerbation; therefore, PSL therapy was gradually increased from 5 mg/day to 20 mg/day, which resulted in the normalization of the TNI level, and no PSL-related side effects occurred. MG easily complicates myocarditis as an immune-related adverse event; thus, the treatment plan should be carefully considered.
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http://dx.doi.org/10.2169/internalmedicine.5412-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946516PMC
February 2021

A case of severe aortic stenosis caused by unicuspid unicommissural aortic valve.

J Cardiol Cases 2020 Oct 11;22(4):170-173. Epub 2020 Jun 11.

Division of Cardiology, Shimane University, Faculty of Medicine, Izumo, Japan.

Unicuspid aortic valve (UAV) is an extremely rare congenital malformation that frequently presents with valvular dysfunction or aortic aneurysm. Here we report the case of a 49-year-old man with severe aortic stenosis caused by UAV requiring the Bentall procedure. Two- and three-dimensional transesophageal echocardiography revealed an eccentric opening in an aortic valve and a lateral attachment to the aorta at the orifice level, suggestive of which is consistent with unicommissural UAV as confirmed by surgical findings. < We report a rare case of unicuspid aortic valve (UAV) requiring the Bentall procedure. This case demonstrates the utility of two- and three-dimensional transesophageal echocardiography in revealing the morphology of UAV, as confirmed by surgical findings.>.
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http://dx.doi.org/10.1016/j.jccase.2020.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520516PMC
October 2020

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for advanced gastric cancer.

Ann Gastroenterol Surg 2020 Sep 16;4(5):540-548. Epub 2020 Jul 16.

Hiroshima City Asa Hospital Hiroshima Japan.

Aim: Neoadjuvant chemotherapy (NAC) is promising to improve the survival of resectable gastric cancer. However, suitable regimen and treatment duration for NAC have not yet been established.

Methods: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and S-1/cisplatin/docetaxel(DCS) using a two-by-two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous-type cancer received two or four courses of SC or DCS. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 eligible patients.

Results: Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). The 3-year OS was 58.1% in CS and 60.0% in DCS with hazard ratio of 0.80 (95% CI, 0.48-1.34), while it was 53.1% in the two courses and 65.0% in the four courses with hazard ratio of 0.72 (95% CI, 0.43-1.22). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% for both two and four courses in CS, while it was 48.5% for two courses of DCS and 71.9% for four courses of DCS.

Conclusions: Considering high 3-year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer.
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http://dx.doi.org/10.1002/ags3.12352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511564PMC
September 2020

A case of prolonged atrial pacing latency.

Eur Heart J Case Rep 2020 Aug 28;4(4):1-2. Epub 2020 Jul 28.

Division of Cardiology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Japan.

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http://dx.doi.org/10.1093/ehjcr/ytaa215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501926PMC
August 2020

Papillary muscle rupture after transcatheter aortic valve implantation.

Catheter Cardiovasc Interv 2020 Sep 23. Epub 2020 Sep 23.

Division of Cardiology, Shimane University Faculty of Medicine, Izumo, Japan.

Catheter-induced mitral regurgitation (MR) caused by mitral papillary muscle rupture can be a fatal complication of transcatheter aortic valve implantation (TAVI). We report a case involving an 89-year-old man who presented with symptomatic severe aortic stenosis. In addition, preoperative echocardiography showed accessory mitral valve tissue. Although moderate MR developed immediately after TAVI, severe MR caused by anterolateral papillary muscle rupture occurred 3 months after TAVI. As only a few case series have been published, our case report adds to the evidence base for this treatment strategy.
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http://dx.doi.org/10.1002/ccd.29252DOI Listing
September 2020

Clarithromycin-induced Coronary Vasospasms Caused Acute Coronary Syndrome in a 19-year-old Male Patient.

Intern Med 2021 Jan 19;60(2):281-285. Epub 2020 Sep 19.

Division of Cardiology, Shimane University Faculty of Medicine, Japan.

A 19-year-old-man was admitted to our hospital with intermittent chest pain. The day before admission, he had been diagnosed with enteritis and prescribed clarithromycin. He had experienced severe chest pain three times after taking clarithromycin; thus, acute coronary syndrome (ACS) was suspected. Emergent coronary angiography showed normal coronary arteries; however, the result of a subsequent acetylcholine provocation test was positive. We diagnosed him to have ACS caused by coronary vasospasms and suspected clarithromycin-induced Kounis syndrome. Although more common in older patients, Kounis syndrome must be suspected and a thorough medication history should be taken whenever a patient complains of chest pain.
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http://dx.doi.org/10.2169/internalmedicine.5548-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872808PMC
January 2021

Complete atrioventricular block and torsade de pointes due to dose-dense epirubicin and cyclophosphamide therapy.

Int Cancer Conf J 2020 Oct 22;9(4):207-211. Epub 2020 Jun 22.

Division of Cardiology, Shimane University Faculty of Medicine, Hamada, Shimane Japan.

The dose-dense epirubicin and cyclophosphamide (EC) therapy for breast cancer decreases the risk of cancer recurrence and death. However, epirubicin and cyclophosphamide also cause cardiotoxicity, and cardiomyopathy is the most well-known related adverse effect. A 58-year-old woman presented to our hospital with palpitations 2 weeks after her final dose-dense EC therapy for breast cancer. Holter electrocardiogram (ECG) showed transitory complete atrioventricular block (CAVB) and torsade de pointes. A 12-lead ECG showed QT prolongation in addition to CAVB. Patients receiving dose-dense EC therapy should be monitored more carefully with ECG due to their risk of fatal arrhythmias.
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http://dx.doi.org/10.1007/s13691-020-00427-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450030PMC
October 2020
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