Publications by authors named "Masashi Tanaka"

338 Publications

Potential Genetic Contributions of the Central Nervous System to a Predisposition to Elite Athletic Traits: State-of-the-Art and Future Perspectives.

Genes (Basel) 2021 Mar 5;12(3). Epub 2021 Mar 5.

Department of Physical Therapy, Health Science University, 7187 Kodachi, Fujikawaguchiko-machi, Minamitsuru-gun, Yamanashi 401-0380, Japan.

Recent remarkable advances in genetic technologies have allowed for the identification of genetic factors potentially related to a predisposition to elite athletic performance. Most of these genetic variants seem to be implicated in musculoskeletal and cardiopulmonary functions. Conversely, it remains unclear whether functions of the central nervous system (CNS) genetically contribute to elite athletic traits, although the CNS plays critical roles in exercise performance. Accumulating evidence has highlighted the emerging implications of CNS-related genes in the modulation of brain activities, including mental performance and motor-related traits, thereby potentially contributing to high levels of exercise performance. In this review, recent advances are summarized, and future research directions are discussed in regard to CNS-related genes with potential roles in a predisposition to elite athletic traits.
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http://dx.doi.org/10.3390/genes12030371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000928PMC
March 2021

Polymorphic SERPINA3 prolongs oligomeric state of amyloid beta.

PLoS One 2021 4;16(3):e0248027. Epub 2021 Mar 4.

Department of Life Sciences and Bioengineering, Laboratory of Molecular and Cellular Biology, Faculty of Engineering, University of Toyama, Toyama, Japan.

Molecular chaperon SERPINA3 colocalizes with accumulated amyloid peptide in Alzheimer's disease (AD) patient's brain. From the QTL analysis, we narrowed down Serpina3 with two SNPs in senescence-accelerated mouse prone (SAMP) 8 strain. Our study showed SAMP8 type Serpina3 prolonged retention of oligomeric Aβ 42 for longer duration (72 hr) while observing under transmission electron microscope (TEM). From Western blot results, we confirmed presence of Aβ 42 oligomeric forms (trimers, tetramers) were maintained for longer duration only in the presences of SAMP8 type Serpina3. Using SH-SY5Y neuroblastoma cell line, we observed until 36 hr preincubated Aβ 42 with SAMP8 type Serpina3 caused neuronal cell death compared to 12 hr preincubated Aβ 42 with SAMR1 or JF1 type Serpina3 proteins. Similar results were found by extending this study to analyze the effect of polymorphism of SERPINA3 gene of the Japanese SNP database for geriatric research (JG-SNP). We observed that polymorphic SERPINA3 I308T (rs142398813) prolonged toxic oligomeric Aβ 42 forms till 48 hr in comparison to the presence wild type SERPINA3 protein, resulting neuronal cell death. From this study, we first clarified pathogenic regulatory role of polymorphic SERPINA3 in neurodegeneration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248027PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932536PMC
March 2021

Taxifolin: A Potential Therapeutic Agent for Cerebral Amyloid Angiopathy.

Front Pharmacol 2021 12;12:643357. Epub 2021 Feb 12.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β-amyloid (Aβ) in the walls of cerebral vessels, leading to complications such as intracerebral hemorrhage, convexity subarachnoid hemorrhage and cerebral microinfarcts. Patients with CAA-related intracerebral hemorrhage are more likely to develop dementia and strokes. Several pathological investigations have demonstrated that more than 90% of Alzheimer's disease patients have concomitant CAA, suggesting common pathogenic mechanisms. Potential causes of CAA include impaired Aβ clearance from the brain through the intramural periarterial drainage (IPAD) system. Conversely, CAA causes restriction of IPAD, limiting clearance. Early intervention in CAA could thus prevent Alzheimer's disease progression. Growing evidence has suggested Taxifolin (dihydroquercetin) could be used as an effective therapy for CAA. Taxifolin is a plant flavonoid, widely available as a health supplement product, which has been demonstrated to exhibit anti-oxidative and anti-inflammatory effects, and provide protection against advanced glycation end products and mitochondrial damage. It has also been shown to facilitate disassembly, prevent oligomer formation and increase clearance of Aβ in a mouse model of CAA. Disturbed cerebrovascular reactivity and spatial reference memory impairment in CAA are completely prevented by Taxifolin treatment. These results highlight the need for clinical trials on the efficacy and safety of Taxifolin in patients with CAA.
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http://dx.doi.org/10.3389/fphar.2021.643357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907591PMC
February 2021

Evaluation of the mechanical properties and biocompatibility of gypsum-containing calcium silicate cements.

Dent Mater J 2021 Feb 27. Epub 2021 Feb 27.

Department of Dental Materials Science, Division of Oral Functional Science and Rehabilitation, Asahi University School of Dentistry.

Mineral trioxide aggregate (MTA) cement is widely used in the field of endodontic treatment. We herein synthesized calcium silicates from calcium carbonate and silicon dioxide, with the aim of reducing the cost associated with the MTA. Additionally, we prepared gypsum-containing calcium silicate cement to reduce the setting time while enhancing the mechanical strength. We evaluated the physical properties of this cement and investigated the response of human dental pulp stem cells (hDPSCs) grown in culture media containing cement eluate. Our results revealed that calcium silicates could be easily synthesized in lab-scale. Furthermore, we demonstrate that gypsum addition helps shorten the setting time while increasing the compressive strength of dental cements. The synthesized gypsum-containing calcium silicate cement showed minimal cytotoxicity and did not inhibit the proliferation of hDPSCs. These results suggested that the newly developed calcium silicate material could be a promising pulp capping material.
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http://dx.doi.org/10.4012/dmj.2020-086DOI Listing
February 2021

Native valve attachment to the prosthetic valve 2.5 years after the 3 tricuspid valve replacement.

Ann Thorac Surg 2021 Feb 16. Epub 2021 Feb 16.

The Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan. Electronic address:

The native tricuspid leaflets are sometimes preserved with tricuspid valve replacement to prevent atrioventricular block or maintain the right ventricular function. However, following a tricuspid valve replacement using bioprosthetic valve, a rare complication involving adhesion of the pannus formation to the prosthetic valve may occur. We report the case of a 48-year-old woman who underwent a third tricuspid valve replacement with a bioprosthetic valve for severe tricuspid regurgitation 2.5 years after the redo tricuspid valve replacement.
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http://dx.doi.org/10.1016/j.athoracsur.2021.02.004DOI Listing
February 2021

D-amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer.

Mol Clin Oncol 2021 Mar 24;14(3):58. Epub 2021 Jan 24.

Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.

Gastric cancer is prevalent in the Asian population. Genetic predisposition to gastric cancer is not fully understood. Recent studies have demonstrated that D-amino acid oxidase (DAO), a multifunctional enzyme, protects the mucosa of gastrointestinal (GI) tracts by generating hydrogen sulfide (HS) in the stomach of rodents. The present study surveyed rare germline variants in the human DAO gene with regard to the incidence of gastric cancer. The consecutive autopsy cases registered in the JG-SNP database (n=2,343; mean age, 80 years) were employed and genotyped with Exome Bead-Chips. There were three non-synonymous rare variants, p.R22H, p.P103L and p.R283Q, of which the minor allele frequencies were 0.09, 0.21 and 0.02%, respectively. Carriers of these variants were surveyed, the results of which revealed that 4 out of 10 patients with the p.P103L variant had gastric cancer (Fisher's exact test, P=0.018). All 4 patients were men with drinking and smoking habits. Among the other 6 women, there was one incidence of small intestine cancer and one of colon cancer. Neither p.R22H nor p.R283Q carriers had GI cancer. DAO p.P103L is reported to be a modifier of amyotrophic lateral sclerosis (ALS) and may potentially be a hypomorphic allele. Thus, it is hypothesized that this rare variant might have affected protection against gastric mucosal damage through HS signaling in the mucosa, which leads to high prevalence of gastric cancer. The role of rare variant DAO p.P103L warrants further investigation in larger cohorts.
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http://dx.doi.org/10.3892/mco.2021.2220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849068PMC
March 2021

Exophytic cavernous hemangioma arising from the right ventricle: Report of a rare case.

Pathol Int 2021 Apr 9;71(4):267-271. Epub 2021 Feb 9.

Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan.

Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.
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http://dx.doi.org/10.1111/pin.13075DOI Listing
April 2021

Grounds for surrogate decision-making in Japanese clinical practice: a qualitative survey.

BMC Med Ethics 2021 Jan 13;22(1). Epub 2021 Jan 13.

Department of Medical Ethics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: In the coming years, surrogate decision-making is expected to become highly prevalent in Japanese clinical practice. Further, there has been a recent increase in activities promoting advance care planning, which potentially affects the manner in which judgements are made by surrogate decision-makers. This study aims to clarify the grounds on which surrogate decision-makers in Japan base their judgements.

Methods: In this qualitative study, semi-structured interviews were conducted to examine the judgement grounds in surrogate decision-making for critical life-sustaining treatment choices in acute care hospitals.

Results: A total of 228 participants satisfied the inclusion criteria, and 15 were selected for interviews. We qualitatively analysed the content of 14 interview transcripts, excluding one that did not meet the inclusion criteria. Based on this analysis, we extracted 4 core categories, 17 categories, 35 subcategories, and 55 codes regarding judgement grounds in surrogate decision-making. The four core categories were as follows: patient preference-oriented factor (Type 1), patient interest-oriented factor (Type 2), family preference-oriented factor (Type 3), and balanced patient/family preference-oriented factor (Type 4). The Type 4 core category represented attempts to balance the preferences of the patient with those of the surrogate decision-maker.

Conclusions: Surrogate decision-makers based their decisions on important aspects related to a patient's life, and they considered not only the patient's preferences and best interests but also their own preferences. As the need for surrogate decisions will increase in the future, decision-makers will need to consider judgement grounds from a more diverse perspective.
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http://dx.doi.org/10.1186/s12910-020-00573-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805133PMC
January 2021

Differential roles of VPS and RAAS in water homeostasis and a risk for kidney dysfunction in rats undergoing rapid fasting/dehydration with regular exercise.

Physiol Rep 2021 01;9(1):e14670

Department of Physical Therapy, Health Science University, Minamitsuru-gun, Japan.

Purpose: We examined the effects of rapid restriction of food and fluid intake on the pathways of water homeostasis, the vasopressinergic system (VPS), and the renin-angiotensin-aldosterone system (RAAS), in rats with or without regular exercise.

Methods: Sprague Dawley rats were divided into the following groups: no intervention, rapid restriction, regular exercise, and rapid restriction combined with regular exercise. Rats in the exercise group performed climbing exercise for 4 weeks. All rats consumed food ad libitum, and those in the rapid restriction group fasted for the last 3 days with no water on the last 1 day.

Results: Despite no significant differences in body weight among the groups, the kidney weight was decreased when rapid restriction and regular exercise were combined. Rapid restriction reduced the urine volume and increased the urine osmolality, whereas regular exercise did not. Rapid restriction but not regular exercise increased the levels of circulating aldosterone and the renal expression levels of the ion channel SGK-1 compared to those without rapid restriction, indicating the stimulation of RAAS. Conversely, VPS showed no significant response to these interventions. Moreover, rapid restriction combined with regular exercise induced the renal expression levels of proinflammatory cytokines and increased the active forms of apoptotic effector caspase-3 compared with the no intervention group.

Conclusions: Functional significance may differ between VPS and RAAS in water homeostasis in response to rapid restriction. Moreover, the combination of rapid restriction and regular exercise has potentially deleterious effects on the kidney.
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http://dx.doi.org/10.14814/phy2.14670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785051PMC
January 2021

A Comparative Prospective Observational Study on the Use of Direct Oral Anticoagulants after Cardiac Surgery for the Management of Atrial Fibrillation.

Ann Thorac Cardiovasc Surg 2020 Nov 18. Epub 2020 Nov 18.

Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan.

Purpose: Recently, guidelines recommended the use of direct oral anticoagulants (DOACs) for the management of non-valvular atrial fibrillation (NVAF). Postoperative atrial fibrillation (POAF) is the most common post-surgical complication of cardiac surgery, but the efficacy and safety of DOAC for POAF have rarely been investigated. We conducted a prospective observational study to investigate the efficacy and safety of DOAC administered immediately after POAF.

Materials And Methods: In all, 135 patients that experienced POAF after cardiac surgery were treated with a DOAC. Primary endpoints were either bleeding or thromboembolic events. Secondary endpoints included changes in hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), serum creatinine (sCr), estimated glomerular filtration rate (eGFR), and pleural/pericardial effusion.

Results: Patients were treated with apixaban (n = 31), edoxaban (n = 87), and rivaroxaban (n = 17). Major bleeding (p = 0.011) and gastrointestinal (GI) bleeding (p = 0.047) were significantly more frequent in the rivaroxaban group. Stroke was observed in one rivaroxaban group patient and none in the other two groups.

Conclusion: DOAC as anticoagulation therapy for the early intervention of POAF following cardiac surgery is associated with a low incidence of major bleeding; a favorable safety profile and excellent efficacy were demonstrated for DOAC. Furthermore, our results indicate that the safety and efficacy of apixaban and edoxaban are better than rivaroxaban.
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http://dx.doi.org/10.5761/atcs.oa.20-00213DOI Listing
November 2020

Erosive polyarthritis caused by sepsis due to a novel species of .

Mod Rheumatol Case Rep 2020 01 5;4(1):95-98. Epub 2019 Sep 5.

Department of Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.

Rat-bite fever (RBF) is characterized by fever, rash and arthritis, mainly caused by . We present a case of inflammatory erosive polyarthritis with sepsis caused by , a novel species isolated from . A 67-year-old man presented with fever, purpura and peripheral arthritis. After blood cultures were performed, loxoprofen administration was initiated. Arthritis partially improved, but left first metatarsophalangeal (MTP) arthritis persisted. A gram-negative rod was detected in the blood culture, and meropenem administration was started that improved arthritis. Ultrasonography and computed tomography revealed bone erosion in the left first MTP joint, leading to the diagnosis of septic arthritis. 16S rRNA gene sequence analysis revealed that this strain was . Further questioning revealed the patient may have had contact with rats. It is essential to consider infection in the differential diagnosis of erosive polyarthritis.
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http://dx.doi.org/10.1080/24725625.2019.1655246DOI Listing
January 2020

Iatrogenic acute aortic dissection caused by intervention for spontaneous coronary artery dissection: a surgical case report.

J Cardiothorac Surg 2020 Sep 29;15(1):280. Epub 2020 Sep 29.

Department of Cardiovascular Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

Background: Iatrogenic acute aortic dissection (AAD) caused by cardiovascular intervention is rare. Also rare is spontaneous coronary artery dissection (SCAD), a form of acute coronary syndrome, which develops in relatively young women without coronary risk factors. We encountered type A iatrogenic AAD caused by an intervention for SCAD.

Case Presentation: A 53-year-old woman was brought to our hospital after cardiopulmonary resuscitation. She was diagnosed with acute coronary syndrome caused by SCAD, and percutaneous coronary intervention was carried out on her distal left anterior descending artery. The dissection proceeded to the proximal left anterior descending artery and left main coronary artery trunk, so additional percutaneous coronary intervention was performed on the left circumflex artery. After the intervention, type A AAD occurred with a primary entry tear from the left main coronary artery trunk, and computed tomography showed a type A AAD of the aortic arch. We performed emergency ascending aorta replacement and coronary artery bypass grafting to the left anterior descending artery and left circumflex artery. The patient had an uneventful recovery after the operation and was discharged on postoperative day 25.

Conclusion: To our knowledge, this is the first report of an iatrogenic AAD caused by percutaneous coronary intervention for SCAD.
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http://dx.doi.org/10.1186/s13019-020-01333-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526354PMC
September 2020

Soft x-ray irradiation induced metallization of layered TiNCl.

J Phys Condens Matter 2020 Sep 25. Epub 2020 Sep 25.

Research Institute for Interdisciplinary Science , Okayama University, Okayama, Okayama, JAPAN.

We have performed soft x-ray spectroscopy in order to study the photoirradiation time dependence of the valence band structure and chemical states of layered transition metal nitride chloride TiNCl. Under the soft x-ray irradiation, the intensities of the states near the Fermi level () and the Ticomponent were increased, while the Cl 2intensity was decreased. Ti 2-3resonance photoemission spectroscopy confirmed a distinctive Fermi edge with Ti 3character. These results indicate the photo-induced metallization originates from deintercalation due to Cl desorption, and thus provide a new carrier doping method that controls the conducting properties of TiNCl.
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http://dx.doi.org/10.1088/1361-648X/abbbc3DOI Listing
September 2020

Suturing Fenestration of the Left Subclavian Artery Orifice in Frozen Elephant Trunk Procedure.

Thorac Cardiovasc Surg 2020 Sep 8. Epub 2020 Sep 8.

Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan.

The frozen elephant trunk (FET) procedure enables easier replacement of the entire aortic arch because it does not require reaching the distal part of the left subclavian artery (LSCA). However, it requires additional management for reconstruction of the LSCA, which is associated with bleeding events. However, the fenestrated FET technique confers a risk of endoleakage from the fenestration site. We report our unique novel technique in which the proximal side of the hybrid stent graft is cut into V-shape around the subclavian artery and sutured continuously around the orifice of the subclavian artery during aortic stump fixation.
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http://dx.doi.org/10.1055/s-0040-1715434DOI Listing
September 2020

Serum growth differentiation factor 15 level is associated with muscle strength and lower extremity function in older patients with cardiometabolic disease.

Geriatr Gerontol Int 2020 Oct 4;20(10):980-987. Epub 2020 Sep 4.

Departments of Diabetes, Metabolism, and Endocrinology, Tokyo, Japan.

Aims: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease.

Methods: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function.

Results: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models.

Conclusions: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.
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http://dx.doi.org/10.1111/ggi.14021DOI Listing
October 2020

Differential effects of sodium-glucose cotransporter 2 inhibitor and low-carbohydrate diet on body composition and metabolic profile in obese diabetic mice.

BMJ Open Diabetes Res Care 2020 09;8(1)

Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organisation Kyoto Medical Center, Kyoto, Japan.

Introduction: Treatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the effects of SGLT2 inhibitor and LCD on body composition and metabolic profile using the mouse model for obesity and type 2 diabetes.

Research Design And Methods: Eight-week-old male mice were divided into four groups: mice receiving normal diet and vehicle or canagliflozin (Cana) administration and mice receiving LCD and vehicle or Cana administration for 8 weeks. Consumed calories were adjusted to be equal among the groups.

Results: Both Cana administration and LCD feeding resulted in significant weight gain. Cana administration significantly decreased plasma glucose levels and increased plasma insulin levels with preservation of pancreatic β cells. However, LCD feeding did not improve plasma glucose levels but deteriorated insulin sensitivity. LCD feeding significantly reduced liver weight and hepatic triglyceride content; these effects were not observed with Cana administration. Combined treatment with LCD did not lead to an additive increase in blood β-ketone levels.

Conclusions: SGLT2 inhibitors and LCD exert differential effects on the body. Their combined use may achieve better metabolic improvements in obesity and type 2 diabetes.
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http://dx.doi.org/10.1136/bmjdrc-2020-001303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473664PMC
September 2020

Factors associated with follow-up difficulty in longitudinal studies involving community-dwelling older adults.

PLoS One 2020 3;15(8):e0237166. Epub 2020 Aug 3.

Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

This study aims to clarify the factors associated with the gradual withdrawal from society in older adults. We defined the stages of follow-up difficulty based on four follow-up surveys on non-respondents of longitudinal mail surveys in community-dwelling older adults to examine the main factors associated with the stages of follow-up difficulty. We conducted a follow-up mail survey (FL1) with respondents of a baseline survey, and three more follow-up surveys with the non-respondents of each previous survey: simplified mail (FL2), postcard (FL3), and home visit surveys (FL4). The respondents of each follow-up survey were defined as a stage of follow-up difficulty; their characteristics concerning social participation and interaction at baseline in each stage were analyzed. The number of respondents in the FL1, FL2, FL3, and FL4 stages and non-respondents (NR) were as follows: 2,361; 462; 234; 84; and 101, respectively. Participation in hobby groups in FL2 and FL3, sports groups in FL4, and neighborhood association and social isolation in NR were significantly associated with the stage of follow-up difficulty. Based on these results, we conclude that the following factors are associated with each stage of follow-up difficulty: 1) a decline in instrumental activities of daily living in the FL2 and FL3 stages, 2) dislike for participating in physical activity such as sports in the FL4 stage, and 3) social isolation, not even belonging to a neighborhood association due to low social interaction in the NR group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237166PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398506PMC
October 2020

Ventricular Septal Rupture After Recent Myocardial Infarction in the Very Elderly.

Int Heart J 2020 ;61(4):831-837

Department of Cardiovascular Surgery, Nihon University School of Medicine.

Ventricular septal rupture (VSR) is one of the fatal complications of myocardial infarction in the percutaneous coronary intervention era. A rapid diagnosis, medical and mechanical support, and surgical intervention are required for recovery and survival. In such a situation, the risk of complications associated with surgery is very high, especially in very elderly patients, in which any therapeutic strategy should be carefully discussed by the heart team. Herein, we describe two cases of VSRs after recent myocardial infarction (RMI) in very elderly patients that required debate regarding whether to perform surgery. The patients included a 93-year-old man and 89-year-old man, both of which were not highly frail before the RMI occurred. In the former case, a conservative strategy was adopted because the risk of surgery was considered, but he did not survive. On the other hand, the latter patient underwent surgery and his life was ultimately saved. Based on these two cases, we concluded that even if the patients are very old, if possible, surgical intervention should be fully considered.
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http://dx.doi.org/10.1536/ihj.20-003DOI Listing
August 2020

Mitochondrial research in Asia: A step for the mito-global conference.

Biochim Biophys Acta Gen Subj 2020 09 29;1864(9):129638. Epub 2020 May 29.

Department of Neurology, Juntendo University Graduate School of Medicine, Bunkyo, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.bbagen.2020.129638DOI Listing
September 2020

The role of ultrasound imaging in operative treatment for a rare case of inferior vena cava tumor.

J Med Ultrason (2001) 2020 07 27;47(3):485-486. Epub 2020 May 27.

Division of Cardiovascular Surgery, Department of Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

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http://dx.doi.org/10.1007/s10396-020-01028-4DOI Listing
July 2020

Pulpal Disease Arising from Medication-related Osteonecrosis of the Jaw: A Case Report.

J Endod 2020 Aug 8;46(8):1149-1154. Epub 2020 May 8.

Department of Endodontics, Division of Oral Functional Science and Rehabilitation, Asahi University School of Dentistry, Mizuho City, Gifu, Japan.

Although bisphosphonates are widely used to treat conditions such as osteoporosis, they may cause osteonecrosis of the jaw. We treated a patient with no history of tooth extraction or other surgical treatment who developed medication-related osteonecrosis of the jaw (MRONJ) with secondary pulpal disease. A 79-year-old woman presented with purulent discharge from the gum at the incisor region. She had been using bisphosphonates for 9 years. Tooth #6 had undertaken root canal treatment at a general practice. All teeth other than tooth #6 reacted to electric pulp testing. Computed tomographic imaging revealed signs suggestive of necrotic bone, and MRONJ was diagnosed. Teeth #7 and #8, which had initially exhibited vital reactions, also subsequently ceased to react to thermal and electric pulp testing. Root canal treatment was performed on teeth #6-8, and their condition was monitored. Computed tomographic imaging at 9 months after the first presentation revealed that the bone defect had greatly enlarged with separation of the necrotic bone; therefore, excision of the necrotic bone and curettage were performed in the department of oral and maxillofacial surgery. The loss of pulp reaction in teeth that had exhibited a vital reaction at the first presentation was considered to indicate that teeth #6-8 had developed dental pulp pathosis as a result of MRONJ.
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http://dx.doi.org/10.1016/j.joen.2020.04.010DOI Listing
August 2020

Clinical Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Infective Endocarditis.

Int Heart J 2020 May 15;61(3):531-538. Epub 2020 May 15.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine.

Risk stratification of patients with infective endocarditis (IE) is difficult. The Controlling Nutritional Status (CONUT) score is an index of immune function and nutritional status. We investigated the prognostic value of the CONUT score in IE and whether its prognostic value differed between IE patients with and without indications for surgery.Clinical records were retrospectively evaluated for 92 patients with IE treated at Nihon University Itabashi Hospital and Nihon University Hospital between January 2014 and May 2019. The CONUT score was determined upon admission, and patients were divided into two groups at the median score (≤ 7 [n = 50] and ≥ 8 [n = 42]). The primary outcome was all-cause mortality at 90 days after admission.The high CONUT group had significantly higher C-reactive protein and N-terminal pro-brain natriuretic peptide levels, as well as a significantly lower hemoglobin and estimated glomerular filtration rate (all P < 0.05), and considerably more valve perforation (26% versus 8%, P < 0.05). Kaplan-Meier analysis revealed that mortality was significantly higher in the high CONUT group (P < 0.001). Even after adjusting for the propensity score based on IE risk factors, a higher CONUT score was still associated with mortality. A receiver-operating characteristic analysis revealed that a CONUT score ≥ 8 had a sensitivity of 86% and specificity of 76% for predicting all-cause mortality. A CONUT score ≥ 8 was most strongly associated with mortality in patients with surgical indications (P < 0.001).In patients with IE, a higher CONUT score was significantly associated with inflammation, heart failure, renal dysfunction, anemia, valve dysfunction, and short-term mortality, especially in patients with surgical indications.
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http://dx.doi.org/10.1536/ihj.19-500DOI Listing
May 2020

Surviving Case of a Blowout-Type Left Ventricular Free Wall Rupture During Percutaneous Coronary Intervention for a Lateral Acute Myocardial Infarction.

Int Heart J 2020 May 15;61(3):606-610. Epub 2020 May 15.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine.

A 76-year-old man suffering from chest pain was admitted to our hospital with a suspected acute myocardial infarction (AMI). Emergent coronary angiography revealed a totally occluded proximal left circumflex artery (LCX). During primary percutaneous coronary intervention, his blood pressure suddenly fell within seconds, and he developed pulseless electrical activity (PEA). Surprisingly, the 12-lead electrocardiogram (ECG) findings including the heart rate remained unchanged before and after the PEA, but a heart rate reduction and asystole occurred a few minutes after developing PEA. After tracheal intubation and mechanical assistance by venoarterial extracorporeal membrane oxygenation (VA-ECMO), the sudden onset of PEA appeared to be caused by cardiac tamponade due to a blowout-type left ventricular free wall rupture (BO-LVFWR) diagnosed by transthoracic echocardiography. While pericardiocentesis was performed and the drained blood was directly continuously perfused intravenously to keep the VA-ECMO flow, the patient was moved to the operation room. The surgical findings revealed a solitary BO-LVFWR due to a lateral AMI, and a direct closure was performed. Successful perioperative management, oral medication administration, and rehabilitation lead to the patient being transferred to a rehabilitation hospital without any serious cerebral damage. This case report suggested the detailed onset pattern of a BO-LVFWR followed by a rapid diagnosis by echocardiography and lifesaving treatment.
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http://dx.doi.org/10.1536/ihj.19-495DOI Listing
May 2020

New Treatment for Driveline Infection Following Implantation of a Ventricular Assist Device.

Heart Surg Forum 2020 03 13;23(2):E132-E134. Epub 2020 Mar 13.

The Department of Cardiovascular Surgery, the Department of Cardiology, Nihon University School of Medicine, Tokyo, Japan.

In patients with an implantable ventricular assist device (VAD), driveline infection (DLI) is a challenging complication. Once DLI occurs, it may lead to pump contamination and/or septicemia, which means that early treatment is essential. We hereby report our initial experiences of a mechanically-powered portable negative pressure wound therapy system (Smart Negative Pressure: SNaPTM) to treat DLI at an outpatient clinic.
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http://dx.doi.org/10.1532/hsf.2899DOI Listing
March 2020

Sport and exercise genomics: the FIMS 2019 consensus statement update.

Br J Sports Med 2020 Aug 22;54(16):969-975. Epub 2020 Mar 22.

Collaborating Centre of Sports Medicine, University of Brighton, Eastbourne, UK

Rapid advances in technologies in the field of genomics such as high throughput DNA sequencing, big data processing by machine learning algorithms and gene-editing techniques are expected to make precision medicine and gene-therapy a greater reality. However, this development will raise many important new issues, including ethical, moral, social and privacy issues. The field of exercise genomics has also advanced by incorporating these innovative technologies. There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. Here, we update a previous consensus and develop a guiding reference for sport and exercise genomics based on a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis. This SWOT analysis and the developed guiding reference highlight the need for scientists/clinicians to be well-versed in ethics and data protection policy to advance sport and exercise genomics without compromising the privacy of athletes and the efforts of international sports federations. Conducting research based on the present guiding reference will mitigate to a great extent the risks brought about by inappropriate use of genomic information and allow further development of sport and exercise genomics in accordance with best ethical standards and international data protection principles and policies. This guiding reference should regularly be updated on the basis of new information emerging from the area of sport and exercise medicine as well as from the developments and challenges in genomics of health and disease in general in order to best protect the athletes, patients and all other relevant stakeholders.
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http://dx.doi.org/10.1136/bjsports-2019-101532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418627PMC
August 2020

Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer's Disease.

Int J Mol Sci 2020 Mar 14;21(6). Epub 2020 Mar 14.

Department of Neurology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease directly implicated in Alzheimer's disease (AD) pathogenesis through amyloid-β (Aβ) deposition, which may cause the development and progression of dementia. Despite extensive studies to explore drugs targeting Aβ, clinical benefits have not been reported in large clinical trials in AD patients or presymptomatic individuals at a risk for AD. However, recent studies on CAA and AD have provided novel insights regarding CAA- and AD-related pathogenesis. This work has revealed potential therapeutic targets, including Aβ drainage pathways, Aβ aggregation, oxidative stress, and neuroinflammation. The functional significance and therapeutic potential of bioactive molecules such as cilostazol and taxifolin have also become increasingly evident. Furthermore, recent epidemiological studies have demonstrated that serum levels of a soluble form of triggering receptor expressed on myeloid cells 2 (TREM2) may have clinical significance as a potential novel predictive biomarker for dementia incidence. This review summarizes recent advances in CAA and AD research with a focus on discussing future research directions regarding novel therapeutic approaches and predictive biomarkers for CAA and AD.
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http://dx.doi.org/10.3390/ijms21061992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139812PMC
March 2020

Desmin-related myopathy characterized by non-compaction cardiomyopathy, cardiac conduction defect, and coronary artery dissection.

ESC Heart Fail 2020 06 6;7(3):1338-1343. Epub 2020 Mar 6.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

Desmin-related myopathy (DRM) is a rare heritable cardiac and skeletal muscle disease caused by mutations in the desmin gene (DES). DRM is generally characterized by skeletal muscle weakness, conduction disturbance, and dilated cardiomyopathy. However, the clinical cardiac phenotypes of DRM are not yet fully understood. Herein, we report the first case of DRM with the de novo missense DES mutation, R454W, that is characterized by left ventricular non-compaction cardiomyopathy, progressive cardiac conduction defect, spontaneous coronary artery dissection, and no skeletal muscle weakness. Our case findings suggest that clinicians should genetically test patients who have cardiomyopathy, progressive cardiac conduction defect, and coronary artery dissection, even if the patient has neither family history of DRM nor skeletal muscle symptoms.
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http://dx.doi.org/10.1002/ehf2.12667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261580PMC
June 2020

Beneficial Effects of Ipragliflozin on the Renal Function and Serum Uric Acid Levels in Japanese Patients with Type 2 Diabetes: A Randomized, 12-week, Open-label, Active-controlled Trial.

Intern Med 2020 1;59(5):601-609. Epub 2020 Mar 1.

Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Japan.

Objective To examine the add-on effects, compared to the existing antidiabetes treatment, of the sodium-glucose cotransporter 2 inhibitor ipragliflozin on glycemic control and the risk factors of cardiovascular disease (CVD) and chronic kidney disease (CKD) in patients with inadequately controlled type 2 diabetes. Methods This 12-week, randomized, open-label, active-controlled trial included 30 patients with type 2 diabetes who were randomized 1:1 to ipragliflozin and control groups (n=15 each). The ipragliflozin group received 50 mg of ipragliflozin once daily in addition to conventional therapy. The primary outcome was the change in hemoglobin A1c (HbA1c) from the baseline. Secondary outcomes were changes from the baseline in indices of glycemic control, uric acid (UA), renal function, and arterial stiffness. Results The patients' diminished estimated glomerular filtration rate (eGFR) was alleviated in the ipragliflozin group compared to the control group [difference between groups (Δ) =4.6 (95% confidence interval (CI): 1.5-7.7) mL/min/1.73 m, p=0.006] prior to significant improvements in HbA1c and other parameters, including anthropometric indices and arterial stiffness. Furthermore, ipragliflozin add-on therapy resulted in a greater reduction in serum UA levels than control therapy [Δ=-52.3 (95% CI: -85.5-19.1) μmol/L, p=0.003]. The changes in the eGFR with ipragliflozin treatment were associated with ipragliflozin-mediated changes in the UA, even after adjusting for the age, sex, baseline HbA1c, baseline UA, and baseline eGFR (standardized regression coefficient=-0.535, p=0.010). Conclusion Ipragliflozin add-on therapy was associated with beneficial renal effects in parallel with reducing serum UA levels.
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http://dx.doi.org/10.2169/internalmedicine.3473-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086326PMC
August 2020

Factors related to white blood cell elevation in acute type A aortic dissection.

PLoS One 2020 6;15(2):e0228954. Epub 2020 Feb 6.

Department of Cardiovascular Surgery, Nihon University, Itabashi-ku, Tokyo, Japan.

Aortic dissection may induce a systemic inflammatory reaction. The etiological backgrounds for elevation of the white blood cell count remain to be clarified. In 466 patients with acute type A aortic dissection treated surgically within 48 hours of symptom onset, the etiologic background of an elevated admission white blood cell count and the effect of such elevation on outcomes were assessed retrospectively. Patients' white blood cell count differed significantly in relation to the extent of dissection, with a median (25th, 75th percentile) white blood cell count of 10.4 (8.1, 13.9) x 103/μL for dissection confined to the ascending aorta, 10.5 (8.2,13.) 103/μL for dissection extending to the aortic arch/descending aorta, 11.1 (8.2, 13.7) x 103/μL for extension to the abdominal aorta, and 13.3 (9.8, 15.9) x 103/μL for extension to the iliac artery (p<0.001). With 11.0 x 103/μL used as the cut-off value for white blood cell count elevation, multivariable analysis showed current smoking (p<0.001; odds ratio, 2.79), dissection extending to the iliac artery (p = 0.006; odds ratio, 1.79), age (p = 0.007, odds ratio, 0.98), and no coronary ischemia (p = 0.027, odds ratio, 2.22) to be factors related to the elevated white blood cell count. Mean age differed significantly between patients with and without an elevated white blood cell count (62.3 vs. 68.3 years, p <0.001). Although in-hospital mortality was similar (7.5% vs.10.9%, p = 0.19), 5-year survival was lower in patients without an elevated count (85.7% vs. 78.6%, p = 0.019), reflecting their more advanced age. In conclusion, our data suggest that dissection morphology and patient age influence the acute phase systemic inflammatory response associated with an elevated white blood cell count in patients with ATAAD. A better understanding of this relation may help optimize diagnosis and perioperative care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228954PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004339PMC
May 2020

The controversy on HPV vaccination in Japan: Criticism of the ethical validity of the arguments for the suspension of the proactive recommendation.

Health Policy 2020 02 26;124(2):199-204. Epub 2019 Dec 26.

Department of Medical Ethics, Tohoku University Graduate School of Medicine, Sendai, Japan.

The Human Papillomavirus (HPV) vaccine was integrated into Japan's national immunization program (NIP) in April 2013. However, numerous instances of serious adverse reactions were widely reported in the media, resulting in the Ministry of Health, Labor, and Welfare (MHLW) suspending the official recommendation of the HPV vaccine on June 14, 2013. Investigating the reported incidents, the Vaccine Adverse Reactions Review Committee (VARRC)-an MHLW advisory committee-found no high-quality evidence supporting a causal relationship between the reported events and the HPV vaccination. However, rather than lifting the suspension, they have opted to maintain a "pseudo informed consent" confirming the perceptions of Japanese citizens regarding the vaccine. Accordingly, there appears to be a fundamental difference in the approach to vaccine policymaking between Japan (MHLW/VARRC) and other countries and the World Health Organization, which base policy decisions on the effectiveness and safety of the vaccine. Consequently, the arguments for the suspension of the HPV vaccine recommendation are not ethically appropriate. Relevant bodies must make a clear decision regarding the HPV vaccine and its status in the NIP: the proactive recommendation must either be reinstated or the HPV vaccine legal framework altered to rely entirely on voluntary individual decisions.
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http://dx.doi.org/10.1016/j.healthpol.2019.12.011DOI Listing
February 2020