1.Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
Michihiro IWAKI ; Hideki FUJII ; Hideki HAYASHI ; Hidenori TOYODA ; Satoshi OEDA ; Hideyuki HYOGO ; Miwa KAWANAKA ; Asahiro MORISHITA ; Kensuke MUNEKAGE ; Kazuhito KAWATA ; Tsubasa TSUTSUMI ; Koji SAWADA ; Tatsuji MAESHIRO ; Hiroshi TOBITA ; Yuichi YOSHIDA ; Masafumi NAITO ; Asuka ARAKI ; Shingo ARAKAKI ; Takumi KAWAGUCHI ; Hidenao NORITAKE ; Masafumi ONO ; Tsutomu MASAKI ; Satoshi YASUDA ; Eiichi TOMITA ; Masato YONEDA ; Akihiro TOKUSHIGE ; Yoshihiro KAMADA ; Hirokazu TAKAHASHI ; Shinichiro UEDA ; Shinichi AISHIMA ; Yoshio SUMIDA ; Atsushi NAKAJIMA ; Takeshi OKANOUE ;
Clinical and Molecular Hepatology 2024;30(2):225-234
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study.
Methods:
This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD.
Results:
Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4).
Conclusions
Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.
2.Saikokaryukotsuboreito Could be Effective Even if Shakanzoto is Ineffective for Paroxysmal Atrial Fibrillation with Strong Palpitation after Cardiac Surgery
Koji KAWAGO ; Yukiyo YOSHIDA ; Satoru SHIRAIWA ; Yoshihiro HONDA ; Kenji SAKAKIBARA ; Shigeaki KAGA ; Hiroyuki NAKAJIMA
Kampo Medicine 2021;72(1):27-33
Paroxysmal atrial fibrillation (pAf) is an arrhythmia that often occurs in the elderly. The quality of life often declines due to severe palpitations caused by pAf. We present a case of recurrent pAf that occurred on postoperative day 2 of coronary artery bypass grafting and pulmonary vein isolation for unstable angina pectoris and pAf. The patient was a 62-year-old man who complained of palpitations, which was consistent with pAf on the monitor ECG. During hospitalization, the patient was constantly wearing an ECG monitor. During pAf, the heart rate was around 120 bpm, and pAf could continue for up to and beyond 24 hours. Paroxysmal atrial fibrillation with strong palpitations was observed every day, even after starting beta-blockers and anticoagulants. After discharge, a Japanese Kampo medicine called shakanzoto was taken for a month, but there was no improvement. After that, it was changed to another Japanese Kampo medicine called saikokaryukotsuboreito, because abdominal examination revealed kyokyokuman (hypochondriac discomfort and distension (resistance)) and saiboki (brisk pulsation in the para-umbilical region). Palpitations quickly improved dramatically. It was speculated that not only palpitations but also pAf had been improved.
3.A Case of Fungal Mycotic Abdominal Aortic Aneurysm with Candida albicans Sepsis
Yoshihiro HONDA ; Yukiyo YOSHIDA ; Koji KAWAGO ; Satoru SHIRAIWA ; Kenji SAKAKIBARA ; Shigeaki KAGA ; Hiroyuki NAKAJIMA
Japanese Journal of Cardiovascular Surgery 2020;49(6):375-379
Background : Fungal mycotic aneurysm is rare ; however, special care and treatment are required for the deep fungal infection itself. Case : The patient was a 69-year-old man with a history of sepsis due to Candida albicans. He suffered from back pain and moderate fever. CT revealed saccular-form aneurysm at the infrarenal abdominal aorta. After emergent in situ bifurcated graft replacement of the infected aneurysm, antifungal treatment was attempted in reference to the antifungal drug sensitivity of C. albicans from intraoperative cultures and findings of fungal endophthalmitis in an ophthalmic examination. After an uneventful acute course, follow up CT images after 12 months postoperatively revealed pseudoaneurysm formation proximal to the site of graft anastomosis. Reoperation was planned with a trans-thoracic and transabdominal approach because of concerns about thoracoabdominal aortic infection. However, the reoperation displayed only inflammatory tissue around the graft and aortic tissue. Removal of the previous graft and reconstruction of the bilateral renal artery, and the pararenal abdominal aorta to the bilateral common iliac artery was performed. Intraoperative tissue cultures revealed no evidence of microorganisms. He returned home with oral antifungal treatment and is doing well at 8 months after the reoperation. Conclusions : Management of fungal mycotic aneurysms requires both surgical treatment and antifungal treatment. Antifungal agents should be selected based on the results of a susceptibility test and after examinations for metastatic comorbidities.
4.Innate immune response of bovine mammary epithelial cells to Mycoplasma bovis
Satoshi GONDAIRA ; Hidetoshi HIGUCHI ; Hidetomo IWANO ; Koji NISHI ; Takanori NEBU ; Keiichi NAKAJIMA ; Hajime NAGAHATA
Journal of Veterinary Science 2018;19(1):79-87
Mycoplasma spp. are contagious bacteria, and mycoplasmal mastitis is a serious productivity problem on dairy farms. Bovine mammary epithelial cells (bMECs) have an important role in the elimination of pathogens, but the effect of Mycoplasma bovis on bMECs has not been fully described. To elucidate the immune response against intramammary infection by M. bovis, we undertook microarray analysis to examine and profile mRNA expression in bMECs after stimulation with M. bovis. We also compared the effects of M. bovis, Staphylococcus aureus, and Escherichia coli on immune-related mRNA expression in bMECs. Transcriptome analysis indicated a significant decrease in the level of mRNA-encoding lysine-specific demethylase 4D, suggesting that the immune response is suppressed by a decrease in histone demethylase activity. Interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, toll-like receptor (TLR) 2, and TLR4 mRNA expression levels were significantly increased in bMECs stimulated with heat-killed M. bovis, but the expression levels were lower than those following stimulation by heat-killed S. aureus or E. coli. Our results suggest that M. bovis weakly affects mRNA expression in bMECs compared to the effects of E. coli or S. aureus. Moreover, live M. bovis may induce suppression of the immune response in bMECs.
Agriculture
;
Bacteria
;
Cytokines
;
Efficiency
;
Epithelial Cells
;
Escherichia coli
;
Female
;
Gene Expression Profiling
;
Histones
;
Immunity, Innate
;
Interleukin-6
;
Interleukins
;
Mastitis
;
Microarray Analysis
;
Mycoplasma bovis
;
Mycoplasma
;
RNA, Messenger
;
Staphylococcus aureus
;
Toll-Like Receptors
;
Tumor Necrosis Factor-alpha
5.Impact of Serum Triglyceride and High Density Lipoprotein Cholesterol Levels on Early-Phase Insulin Secretion in Normoglycemic and Prediabetic Subjects.
Masanori SHIMODAIRA ; Tomohiro NIWA ; Koji NAKAJIMA ; Mutsuhiro KOBAYASHI ; Norinao HANYU ; Tomohiro NAKAYAMA
Diabetes & Metabolism Journal 2014;38(4):294-301
BACKGROUND: Increased triglycerides (TGs) and decreased high density lipoprotein cholesterol (HDL-C) levels are established as diabetic risks for nondiabetic subjects. The aim of this study was to investigate the relationship among TG, HDL-C, TG/HDL-C ratio, and early-phase insulin secretion in normoglycemic and prediabetic subjects. METHODS: We evaluated 663 Japanese subjects who underwent the 75-g oral glucose tolerance test. On the basis of these results, the subjects were divided into four groups: those with normal glucose tolerance (NGT; n=341), isolated impaired fasting glucose (i-IFG; n=211), isolated impaired glucose tolerance (i-IGT; n=71), and combined IFG and IGT (IFG+IGT; n=40). Insulin secretion was estimated by the insulinogenic index (IGI) (Deltainsulin/Deltaglucose [30 to 0 minutes]) and disposition index (DI) (IGI/homeostasis model assessment of insulin resistance). RESULTS: In prediabetic subjects (i-IFG, i-IGT, and IFG+IGT), linear regression analyses revealed that IGI and DI were positively correlated with HDL-C levels. Moreover, in subjects with i-IGT and (IFG+IGT), but not with i-IFG, the indices of insulin secretion were negatively correlated with the log-transformed TG and TG/HDL-C ratio. In both the subjects with i-IGT, multivariate linear regression analyses revealed that DI was positively correlated with HDL-C and negatively with log-transformed TG and TG/HDL-C ratio. On the other hand, in subjects with NGT, there was no association between insulin secretion and lipid profiles. CONCLUSION: These results revealed that serum TG and HDL-C levels have different impacts on early-phase insulin secretion on the basis of their glucose tolerance status.
Asian Continental Ancestry Group
;
Cholesterol, HDL*
;
Fasting
;
Glucose
;
Glucose Tolerance Test
;
Hand
;
Humans
;
Insulin*
;
Linear Models
;
Triglycerides*
6.Early Effect of Single-dose Sitagliptin Administration on Gastric Emptying: Crossover Study Using the 13C Breath Test.
Takashi NONAKA ; Yusuke SEKINO ; Hiroshi IIDA ; Eiji YAMADA ; Hidenori OHKUBO ; Eiji SAKAI ; Takuma HIGURASHI ; Kunihiro HOSONO ; Hiroki ENDO ; Tomoko KOIDE ; Hirokazu TAKAHASHI ; Koji FUJITA ; Masato YONEDA ; Ayumu GOTO ; Akihiko KUSAKABE ; Noritoshi KOBAYASHI ; Eiji GOTOH ; Shin MAEDA ; Atsushi NAKAJIMA ; Chihiro NOSAKA ; Masahiko INAMORI
Journal of Neurogastroenterology and Motility 2013;19(2):227-232
BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests
;
Cross-Over Studies
;
Eating
;
Gastric Emptying
;
Gastrointestinal Motility
;
Humans
;
Incretins
;
Male
;
Meals
;
Pyrazines
;
Triazoles
;
Sitagliptin Phosphate
7.Two advanced cancer patients in whom escitalopram was useful for depression
Shinichiro Nakajima ; Hitoshi Tanimukai ; Mika Baba ; Koji Amano ; Muneyoshi Kawasaki ; Hiroshi Wakayama
Palliative Care Research 2013;8(2):548-553
Purpose: Escitalopram has been inadequately evaluated in cancer patients. Here, we report two patients with advanced cancer who benefited from escitalopram for depression. Case 1: A man aged in his 50s had postoperative recurrence of rectal cancer. He was diagnosed with a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). The score of the Hamilton Rating Scale for Depression (HAMD-17) was 20 points. He began treatment with 10 mg/day of escitalopram. His symptoms began to improve at about 14 days, and the HAMD-17 score was 4 points at 23 days, suggesting a marked improvement. Case 2: A woman aged in her 50s had cancer of the external auditory canal. She was diagnosed with a major depressive episode according to DSM-IV-TR. The score of HAMD-17 was 26 points. She began treatment with 10 mg/day of escitalopram. Her symptoms began to improve at 15 days, and the HAMD-17 score at 28 days was 13 points, suggesting a marked improvement. In both cases, serious side effects, clear exacerbation of depression, and withdrawal syndrome due to acute drug deprivation associated with worsening of the symptoms were not noted. Conclusion: Escitalopram is considered a useful drug for depression in patients with advanced cancer.
8.A study of the significance of death conferences in the palliative care unit : through the experience of coping with the death of a liver cancer patient who died of necrotizing fasciitis resulted from bedsore
Koji Amano ; Mika Baba ; Takashi Sugiura ; Muneyoshi Kawasaki ; Shinichiro Nakajima ; Hiroshi Wakayama ; Akiko Watakabe ; Hiromi Kunimoto ; Miwako Uemori
Palliative Care Research 2012;7(2):568-574
When patients hospitalized in a palliative care unit die, particularly when their deaths were not peaceful ones, we, as health professionals, feel distressed, senses of helplessness and defeat, and even regret. However, busy daily clinical practice usually does not allow us to express these feelings. After going through such an experience repeatedly, your self-efficacy may be reduced and you could feel burned out. In this study, through the experience of coping with the death of a liver cancer patient who died of necrotizing fasciitis resulted from bedsore, a death conference was organized for us, health professionals who had been directly concerned with the patient, to discuss questions, conflicts, and dilemmas that arose when we provided care and express feelings that had been repressed. And other participants in the conference, who had not been directly concerned with the patient, gave their affirmative views. The conferences served to: (1) promote mutual understanding, trustful relationships, and teamwork among us, (2) increase our awareness of palliative care, and (3) allow us to cope with stress and prevent us from feeling burned out. These effects are considered to help implement improved health care. In the former part of the conference remarks were divided into three categories, (1) regret, (2) questions, conflicts, and dilemmas, and (3) senses of helplessness and defeat, and in the latter part affirmative views were mainly stated.
9.Effects of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors on the Rate of Gastric Emptying: A Crossover Study Using a Continuous Real-Time 13C Breath Test (BreathID System).
Takashi NONAKA ; Takaomi KESSOKU ; Yuji OGAWA ; Kento IMAJYO ; Shogo YANAGISAWA ; Tadahiko SHIBA ; Takashi SAKAGUCHI ; Kazuhiro ATSUKAWA ; Hisao TAKAHASHI ; Yusuke SEKINO ; Eiji SAKAI ; Takashi UCHIYAMA ; Hiroshi IIDA ; Kunihiro HOSONO ; Hiroki ENDO ; Yasunari SAKAMOTO ; Koji FUJITA ; Masato YONEDA ; Tomoko KOIDE ; Hirokazu TAKAHASHI ; Chikako TOKORO ; Yasunobu ABE ; Eiji GOTOH ; Shin MAEDA ; Atsushi NAKAJIMA ; Masahiko INAMORI
Journal of Neurogastroenterology and Motility 2011;17(3):287-293
BACKGROUND/AIMS: The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous 13C breath test (BreathID system, Exalenz Bioscience Ltd, Israel). METHODS: Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of 13C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the 13C-acetic acid breath test performed using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, the T1/2, Tlag, GEC, beta and kappa, were observed among the 3 test conditions. CONCLUSIONS: The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.
Acceleration
;
Administration, Intravenous
;
Breath Tests
;
Cross-Over Studies
;
Eating
;
Famotidine
;
Fasting
;
Gastric Acid
;
Gastric Emptying
;
Gastrointestinal Motility
;
Humans
;
Male
;
Meals
;
Mouth
;
Omeprazole
;
Peptic Ulcer
;
Proton Pump Inhibitors
;
Proton Pumps
;
Protons
;
Stress, Psychological
10.Mosapride Accelerates the Delayed Gastric Emptying of High-Viscosity Liquids: A Crossover Study Using Continuous Real-Time 13C Breath Test (BreathID System).
Yasunari SAKAMOTO ; Yusuke SEKINO ; Eiji YAMADA ; Hidenori OHKUBO ; Takuma HIGURASHI ; Eiji SAKAI ; Hiroshi IIDA ; Kunihiro HOSONO ; Hiroki ENDO ; Takashi NONAKA ; Tamon IKEDA ; Koji FUJITA ; Masato YONEDA ; Tomoko KOIDE ; Hirokazu TAKAHASHI ; Ayumu GOTO ; Yasunobu ABE ; Eiji GOTOH ; Shin MAEDA ; Atsushi NAKAJIMA ; Masahiko INAMORI
Journal of Neurogastroenterology and Motility 2011;17(4):395-401
BACKGROUND/AIMS: The administration of liquid nutrients to patients is often accompanied by complications such as gastroesophageal reflux. To prevent gastroesophageal reflux, high-viscosity liquid meals are used widely, however, it still remains controversial whether high-viscosity liquid meals have any effect on the rate of gastric emptying. The present study was conducted with the aim of determining whether high-viscosity liquid meals had any effect on the rate of gastric emptying and mosapride might accelerate the rate of gastric emptying of high-viscosity liquid meals. METHODS: Six healthy male volunteers underwent 3 tests at intervals of > 1 week. After fasting for > 8 hours, each subject received one of three test meals (liquid meal only, high-viscosity liquid meal [liquid meal plus pectin] only, or high-viscosity liquid meal 30 minutes after intake of mosapride). A 13C-acetic acid breath test was performed, which monitored the rate of gastric emptying for 4 hours. Using the Oridion Research Software (beta version), breath test parameters were calculated. The study parameters were examined for all the 3 test conditions and compared using the Freidman test. RESULTS: Gastric emptying was significantly delayed following intake of a high-viscosity liquid meal alone as compared with a liquid meal alone; however, intake of mosapride prior to a high-viscosity liquid meal was associated with a significantly accelerated rate of gastric emptying as compared with a high-viscosity liquid meal alone. CONCLUSIONS: This study showed that high-viscosity liquid meals delayed gastric emptying: however, mosapride recovered the delayed rate of gastric emptying by high-viscosity liquid meals.
Benzamides
;
Breath Tests
;
Cross-Over Studies
;
Fasting
;
Gastric Emptying
;
Gastroesophageal Reflux
;
Humans
;
Male
;
Meals
;
Morpholines
;
Pectins


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