Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy.

Background: The clinical course of esophagogastric varices (EGV) after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy has not been clearly elucidated. The predictors for the worsening/improvement of EGV after SVR with DAA therapy were investigated.

Methods: Of the cirrhosis patients who achieved SVR with DAA therapy, 328 patients who underwent endoscopic examinations both before and after DAA therapy were enrolled.

PKR associates with 4.1R to promote anchorage-independent growth of hepatocellular carcinoma and lead to poor prognosis.

RNA-dependent protein kinase (PKR) may have a positive regulatory role in controlling tumor growth and progression in hepatocellular carcinoma (HCC). However, the downstream substrates and the molecular mechanism of PKR in the growth and progression of HCC have not been clarified. In this study, mass spectrometry analysis was performed with immunoprecipitated samples, and 4.

Association between serum remnant cholesterol level and metabolic dysfunction-associated steatotic liver histology.

Context: Estimated remnant cholesterol (Rem-C) level, a risk factor for cardiovascular disease (CVD), is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosed via ultrasonography. However, the relationship between accurate serum Rem-C level measurements and histological findings of MASLD remains unclear.

Objective: We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD.

Novel mimetic tissue standards for precise quantitative mass spectrometry imaging of drug and neurotransmitter concentrations in rat brain tissues.

Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research.

Diagnostic accuracy of ultrasound-derived fat fraction for the detection and quantification of hepatic steatosis in patients with liver biopsy.

Purpose: This retrospective study was conducted to investigate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) for grading hepatic steatosis using liver histology as the reference standard.

Methods: Seventy-three patients with liver disease were assessed using UDFF and liver biopsy. Pearson's test and the Bland-Altman plot were used to assess the correlation between UDFF and histological fat content in liver sections.

Association of oral frailty with medical expenditure in older Japanese adults: The study of late-stage older adults in Tottori (START Tottori).

Objects: This study aimed to determine the association between annual medical expenses and oral frailty in later-stage older adults (aged ≥ 75 years). No studies have investigated the association between medical costs and oral frailty, which would elucidate the association between oral frailty and the deterioration of mental and overall physical function.

Materials And Methods: In this cross-sectional study, 2190 adults (860 men and 1330 women aged 75-94 years) covered by the Medical System for the Elderly and residing in Tottori Prefecture, Japan, between April 2016 and March 2019, were included.

Discovery and Model-Informed Drug Development of a Controlled-Release Formulation of Nonracemic Amisulpride that Reduces Plasma Exposure but Achieves Pharmacodynamic Bioequivalence in the Brain.

Nonracemic amisulpride (SEP-4199) is an investigational 85:15 ratio of aramisulpride to esamisulpride and currently in clinical trials for the treatment of bipolar depression. During testing of SEP-4199, a pharmacokinetic/pharmacodynamic (PK/PD) disconnect was discovered that prompted the development of a controlled-release (CR) formulation with improved therapeutic index for QT prolongation. Observations that supported the development of a CR formulation included (i) plasma concentrations of amisulpride enantiomers were cleared within 24-hours, but brain dopamine D2 receptor (D2R) occupancies, although achieving stable levels during this time, required 5 days to return to baseline; (ii) nonracemic amisulpride administered to non-human primates produced significantly greater D2R occupancies during a gradual 6-hour administration compared with a single bolus; (iii) concentration-occupancy curves were left-shifted in humans when nonracemic amisulpride was gradually administered over 3 and 6 hours compared with immediate delivery; (iv) CR solid oral dose formulations of nonracemic amisulpride were able to slow drug dissolution in vitro and reduce peak plasma exposures in vivo in human subjects.

Oral frailty, appetite and dietary variety in late-stage older adults: A cross-sectional study (the STudy of lAte-stage oldeR adulTs in Tottori; START Tottori).

Aim: Efforts to combat frailty and preserve good health in older adults have highlighted oral frailty as an early indicator of overall frailty. Individuals showing oral frailty are at an elevated risk of insufficient nutritional intake compared with those without oral frailty; however, underlying mechanisms remain poorly explored. In this cross-sectional study, we aimed to examine the link between oral frailty and undernutrition, especially regarding poor appetite and low dietary diversity.

Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

Aim: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events.

Methods: A total of 282 patients with liver biopsy-proven MASLD were included.

Incidence of venous thromboembolism after cardiovascular surgery.

Background: Among venous thromboembolism, pulmonary thromboembolism (PTE) is one of the most serious postoperative complications. Deep venous thrombosis (DVT) is the main cause. Considering the unknown prevalence of DVT and PTE in the postoperative period of cardiovascular surgery in Japan, we investigated the incidence in consecutive patients who underwent cardiovascular surgery.

The role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease: A scoping review protocol.

Introduction: The number of patients with chronic kidney disease is increasing worldwide; previous studies have suggested that advanced practice nurses, including nurse practitioners and clinical nurse specialists, with expert practice skills can provide high-quality care and solve complex healthcare problems. In general, nurse practitioners are generalist nurses who work as autonomous clinicians with whole personal care. Clinical nurse specialists, in contrast, are nurses with advanced nursing knowledge and skills for individuals or specific populations.

Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease.

Backgruound: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD.

Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy.

A case of hepatocellular carcinoma with pseudoaneurysm formation upon lenvatinib administration.

A 79-year-old man received treatment for multiple intrahepatic hepatocellular carcinoma with atezolizumab + bevacizumab. However, he developed lower back pain attributed to spinal metastases upon tumor enlargement; thus, he was admitted to our hospital for a change from atezolizumab + bevacizumab to lenvatinib and radiation therapy for the spinal metastases. On the 11th day after starting lenvatinib treatment, a pulsatile aneurysm appeared in the tumor, detected using abdominal ultrasonography Micro B-flow imaging, which visualized blood flow at a high frame rate; this was diagnosed as a pseudoaneurysm.

Clinical and Pathological Features of Immune Checkpoint Inhibitor-induced Liver Injury in Comparison with Drug-induced Liver Injury and Autoimmune Hepatitis.

Background And Aims: Immune checkpoint inhibitors may cause various types of organ damage as immune-related adverse events, of which, liver damage is the most common. Herein, we evaluated the clinicopathological features of immune checkpoint inhibitor-related liver injury and investigated the differences between immune checkpoint inhibitor-related liver injury and drug-induced liver injury or autoimmune hepatitis.

Methods: We selected patients with ≥ grade 3 liver injury who were diagnosed with immune checkpoint inhibitor-related liver injury (n=15).

Plasma Gel Made of Platelet-Poor Plasma: In Vitro Verification as a Carrier of Polyphosphate.

Plasma gel (PG) is a blood-derived biomaterial that can be prepared by heating or chemical cross-linking without the aid of intrinsic coagulation activity and has gradually been applied in the field of esthetic surgery. To explore the applicability of PG in regenerative therapy or tissue engineering, in this study, we focused on the advantages of the heating method and verified the retention capacity of the resulting PG for polyphosphate (polyP), a polyanion that contributes to hemostasis and bone regeneration. Pooled platelet-poor plasma (PPP) was prepared from four healthy male adult donors, mixed with synthetic polyP, and heated at 75 °C for 10 or 30 min to prepare PG in microtubes.

Survival Improvements in Advanced Hepatocellular Carcinoma with Sequential Therapy by Era.

Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022.

Metformin-suppressed platelet's function in vitro: Possible relation to delayed or failure of platelet-rich fibrin preparation.

Platelet-rich fibrin (PRF) is a popular autologous blood-derived biomaterial that is used in regenerative therapy. Owing to its simple preparation without additional factors, the PRF quality directly reflects the characteristics of individual blood samples. Antiplatelet or anticoagulant drugs can hamper the successful preparation of PRF.

Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.

Background: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression.

Methods: This was a prospective cross-sectional study that enrolled a total of 199 patients.

Estimation of contribution of CYP2D6 to tipepidine metabolism in humans and prolongation of the half-life of tipepidine by combination use with a CYP2D6 inhibitor in chimeric mice with humanised liver.

Recently, it has been reported that tipepidine has various central pharmacological effects and can be expected to be safely repositioned as a treatment for psychiatric disorders. Since tipepidine has a very short half-life and requires three doses per day, the development of a once-daily medication would be highly beneficial to improve adherence and quality of life in patients with chronic psychiatric disorders. The aim of this study was to identify the enzymes involved in tipepidine metabolism and to verify that combination use with an enzyme inhibitor prolongs the half-life of tipepidine.

Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals.

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients).

Hepatocellular Carcinoma Showing Tumor Shrinkage Due to an Abscopal Effect.

We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

Aim: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance.