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.

A premature boy was born after 35 weeks gestation (1,561 g in weight) with a diagnosis of anomalous origin of the right pulmonary artery from the ascending aorta (AORPA) and perimembranous ventricular septal defect (VSD). The fourteenth day after birth, banding of the right pulmonary artery was performed as a palliative operation. At the age of 5 months (3.9 kg in weight), the right pulmonary artery branched from the ascending aorta, and was anastomosed to a flap made by the lateral wall of the main pulmonary artery with pericardial patch augmentation. VSD patch closure was performed concomitantly. Severe stenosis of the right pulmonary artery compressed by the ascending aorta and left pulmonary hypertension were revealed 3 weeks after the repair. At the age of 11 months, a surgical relief of the right pulmonary artery stenosis was performed. Transection of the ascending aorta provided an excellent exposure of the right posterior pulmonary artery. After patch plasty of the stenotic pulmonary artery, the divided ascending aorta was restored using a strip form patch on 4/5 circle of its posterior wall to extend the aorta and widen the space for the right pulmonary artery. This technique preserves growth potential of the ascending aorta. There are few reports of surgical repair of AORPA with VSD in low birth weight infants. We presented here a case with surgical relief of post-operative right pulmonary artery stenosis. Long term observation of repaired right pulmonary artery, and requiring residual slight hypertension of the left pulmonary artery.

A 48-year old man consulted a doctor at a nearby medical clinic due to dyspnea and increased body mass which he began to experience in October, 2011. Further evaluation revealed the presence of three-vessel severe coronary artery disease, poor left ventricular function, and mitral valve regurgitation. Transthoracic echocardiography showed anterior wall asynergy and left ventricular enlargement. Reconstruction of the left ventricle was contemplated during the preoperative evaluation. The patient underwent hemodialysis for chronic renal failure prior to admission. Generally, delayed gadolinium-enhanced MRI is used for cardiac viability assessment. However, gadolinium is contraindicated in a patient with chronic renal failure owing to the risk of development of nephrogenic systemic fibrosis. Thus, gadolinium-enhanced MRI is contraindicated in the patient. Instead, we used fluorodeoxyglucose-positron emission tomography (FDG-PET) computed tomography (CT) to assess myocardial viability. Consequently, viability was assessed except for a part of the apical electrode in the left anterior descending artery territory. Subsequently, revascularization and mitral valve annuloplasty with coronary artery bypass grafting of five vessels were performed in January, 2012 without left ventricular reconstruction. A left ventricular assist device was used postoperatively, from which he was later weaned. The outcome was good because post-operative left ventriculography revealed improvement in left ventricular wall motion. This case is presented including bibliographical comments on the effectiveness of FDG PET-CT for assessment of myocardial viability.

In Mongolian gerbils, bilateral common carotid artery occlusion (BCCAO) for several minutes induces ischemia, due to an incomplete circle of Willis, resulting in delayed neuronal cell death in the Cornet d'Ammon 1 (CA1) region of the hippocampus. Neuronal cell death in the hippocampus and changes in behavior were examined after BCCAO was performed for 5 min in the gerbils. One day after BCCAO, the pyramidal neurons of the CA1 region of the hippocampus showed degenerative changes (clumped chromatin in nuclei). At 5 and 10 days after BCCAO, extensive neuronal cell death was observed in the hippocampal CA1 region. Cognitive performance was evaluated by using the radial maze and passive avoidance tests. In the radial maze test, which examines win-stay performance, the number of errors was significantly higher in ischemic gerbils than in sham-operated gerbils on days 1 and 2 post-operation. In the passive avoidance test, the latency and freezing times were significantly shorter in ischemic gerbils than in sham-operated gerbils on the days 1, 2, and 4–6 post-operation. These results indicate that transient forebrain ischemia impairs cognitive performance, even immediately after the ischemic insult when there are only subtle signs of neuronal cell death.
CA1 Region, Hippocampal ; Carotid Artery, Common ; Cell Death ; Chromatin ; Circle of Willis ; Freezing ; Gerbillinae ; Hippocampus ; Ischemia ; Neurons ; Prosencephalon ; Pyramidal Cells

A 66-year-old man with an unknown medical history developed chest pain and a diagnosis of acute myocardial infarction (AMI) was given by his physician. Percutaneous coronary intervention was performed in the left anterior descending artery. Echocardiography revealed ventricular septal perforation (VSP) ; therefore, the patient was transferred to our hospital. After admission, his platelet count dropped rapidly during heparin administration, and left ventricular thrombosis and deep vein thrombosis were noted, raising a suspicion of heparin-induced thrombocytopenia (HIT). To establish cardiopulmonary bypass, argatroban alone was insufficient to prolong the Powered by Editorial Manager^® and ProduXion Manager^® from the Aries Systems Corporation activated clotting time (ACT) ; thus, nafamostat mesilate was also used for coronary artery bypass grafting and surgical repair of VSP. It took many hours to normalize the ACT, requiring re-exploration for excessive bleeding. On the 37th postoperative day, the patient was transferred to another hospital. We performed cardiac surgical procedures using argatroban in a patient who developed HIT during the course of VSP following AMI ; however, we had difficulty in controlling the ACT. Since, to the best of our knowledge, there are no previous studies reporting surgical case of VSP complicated by HIT, we present this case with a review of the relevant literature.

Extracts of 16 natural medicine powders (Galla chinensis, Malloti cortex, Cassiae semen, Sophorae radix, Myricae cortex, Crataegi fructus, Gambir, Mume fructus, Geranii herba, Phellodendri cortex, Coptidis rhizoma, Swertiae herba, and Cinnamomi cortex) were assayed for reactive oxygen concentrations using the per-oxyoxalate chemiluminescent detection system. High luminescence intensity was observed in Galla chinensis, Geranii herba, Malloti cortex, Myricae cortex, and Cinnamomi cortex. Additional experiments identified the reactive oxygen species as hydrogen peroxide. Galla chinensis generated 2.4 ? 10 ? 4 mol/L hydrogen peroxide from a 1 mg/mL solution. In bacterial growth tests, Galla chinensis extract had antibacterial activity against Escherichia coli, Staphylococcus aureus, Bacteroides thetaiotaomicron, Campylobacter sputorum biovar sputorum, Streptococcus salivarius thermophilus, Lactobacillus casei, and Bifidobacterium longum infantis. This antibacterial activity was de-creased by the addition of catalase. It revealed that hydrogen peroxide which Galla chinensis produced participated in antibacterial activity.

A Task Force team consisting of members from pharmaceutical companies --a central player to develop and implement RMP (Risk Management Plan)-- as well as health care professionals and members from academia was established in JSPE. The Task Force developed guidance for scientific approach to practical and ICH-E2E-compliant Pharmacovigilance Plan (PVP) stated in Japanese Risk Management Plan issued in April 2012 by the Ministry of Health, Labour and Welfare. The guidance contains the following topics.
1．Introduction: JSPE's activities and this task force's objectives for pharmacovigilance activities
2．How to select Safety Specification (SS) and describe its characteristics
・Selection of SS
・Characterization of SS
・Association with Research Questions (RQ)
3．How to define and describe RQ
・What is RQ ?
・RQ interpretation in other relevant guidelines
・Methodology to develop RQ for PVP with examples
・Best approach to integrating PVP for whole aspects of safety concern
4．How to optimize PVP for specific RQ
・Routine PVP or additional PVP ?
・Additional PVP design (RQ and study design, RQ structured with PICO or GPP's research objectives, specific aims, and rationale)
・Checklist to help develop PVP
5．Epilogue:
・What can/should be “Drug use investigation” in the context of ICH-E2E-compliant PVP.
・Significance of background incidence rate and needs for comparator group
・Infrastructure for the future PVP activities
6．Appendix: Checklist to help develop PVP activities in RMP
The task force team is hoping that this guidance help develop and conduct SS and PVP in accordance with ICH E2E, as stated in Japanese Risk Management Plan Guideline.