Experimental and Computational Insights into the Catalytic Mechanism of Y1-xBaxCoO3-δ Perovskite Oxides with a Controlled Crystal Structure.

The crystal structure of Co-based perovskite oxides (ACoO3) can be controlled by adjusting the A-site elements. In this study, we synthesized Y1-xBaxCoO3-δ (x = 0, 0.5, and 1.0) via a coprecipitation method and investigated their CO oxidation performances. YCoO3 (x = 0; cubic perovskite oxide; Pbnm) shows a higher catalytic performance than Y0.5Ba0.5CoO2.72 (x = 0.5; A-site-ordered double perovskite oxide; P4/nmm), which exhibits high oxygen nonstoichiometric properties, and BaCoO3 (x = 1.0; hexagonal perovskite oxide; P63/mmc), which contains high-valent Co4+ species. To elucidate the reaction mechanism, we conducted isotopic experiments with CO and 18O2. The CO oxidation reaction on YCoO3 proceeds via the Langmuir-Hinshelwood mechanism, which is a surface reaction of CO and O2 gas that does not utilize lattice oxygen. Because of the significantly smaller specific surface area of YCoO3 compared with that of the reference Pt/Al2O3, the bulk features of the crystal structures affect the catalytic reaction. When density functional theory is applied, YCoO3 clearly exhibits semiconducting properties in the ground state with the diamagnetic t2g6eg0 states, which can translate to a magnetic t2g5eg1 configuration upon excitation by a relatively low energy of 0.64 eV. We propose that the unique nature of YCoO3 activates oxygen in the gas phase, thereby enabling the smooth oxidation of CO. This study demonstrates that the bulk properties originating from the crystal structure contribute to the catalytic activity and reaction mechanism.

The Association of Bohler's Angle With Postoperative Pain and Gender for Displaced Intra-Articular Calcaneal Fracture, Multicenter Retrospective Study-TRON Study.

A relationship between Böhler angle (BA) before or after surgery and clinical outcomes remains unclear. This retrospective multicenter cohort study aimed to compare pain and functional outcomes between a group in which the reduction angle was preserved and a group in which the reduction angle was lost during follow-up, and to clarify the risk factors leading to loss of last follow-up BA. From 2014 to 2018, 271 cases of calcaneal fractures were surgically treated at ten facilities. We divided patients into Group L (lost reduction of fracture) and Group P (preserved reduction of fracture). We matched subjects between the 2 groups according to age, sex and BA before surgery and compared American Orthopedic Foot and Ankle Society (AOFAS) score between the groups. We investigated the correlation between the amount of BA loss and postoperative pain. The factors leading to loss of last follow-up BA were examined by logistic regression analysis. Ultimately, 112 patients were eligible. After matching, each group included 38 patients. There was no difference between the 2 groups in total AOFAS score. However, the pain component of AOFAS score at 6 months and 12 months were worse in group L than in group P (p = .011, p = .031, respectively). We also showed a weak correlation between the amount of BA loss and postoperative pain. Logistic regression analysis revealed that female and BA before surgery independently predicted loss of reduction (odds ratios: 4.66, 95% CI: 1.15-18.9 and odds ratios: 0.90, 95% CI: 0.82-0.99, respectively). We clarified that reduction and preservation of BA within its normal range should lead to decrease postoperative pain. Female and lower pre-BA were risk factors leading to loss of reduction of BA in operative treatment of calcaneal fractures.

Plate fixation through the lateral extensile approach versus cannulated screw fixation through the sinus tarsi approach for calcaneal fracture: a multicenter, propensity score-matched TRON study.

PURPOSE: For calcaneal fracture, plate fixation through lateral extensive approach (LEP) is the most common procedure performed to achieve anatomic reduction. However, wound complications sometimes occur after LEP. To reduce complications, minimally invasive operative methods with cannulated screw fixation through sinus tarsi approach (STS) were developed. The aim of this multicenter propensity-matched study was to compare the clinical and radiographic outcomes of LEP to those of STS for calcaneal fracture and to evaluate the incidence of postoperative complications including surgical site infection (SSI). METHODS: We extracted 271 patients with calcaneal fracture undergoing surgery between January 2014 and March 2019 from our multicenter TRON database. We assessed the American Orthopedic Foot and Ankle Society (AOFAS) score at the final follow-up as the clinical outcome. We obtained the Bohler and Preis angles as radiographic parameters and also recorded the complications. We divided the subjects into two groups: LEP group and STS group. To adjust for baseline differences between the groups, a propensity score matching algorithm was used in a 1:1 ratio. RESULTS: After matching, there were 32 fractures in each group. There was no significant difference between the LEP versus STS group in AOFAS score at final follow-up (90 vs 90 points, p = 0.98) and in the Bohler and Pries angles (19.2 vs. 18.0 degrees, p = 0.74 and 16.0 vs. 17.5 degrees, p = 0.47). The rate of SSI in the LEP group was higher than that in the STS group (21.9% vs. 0.0%, p = 0.01). CONCLUSION: For calcaneal fracture, STS provides similar fixation effectiveness and functional outcomes as LEP while reducing the likelihood of infection.

Serum copeptin level is a biomarker associated with ascites retention and the formation of a portosystemic shunt in chronic liver disease.

BACKGROUND AND AIM: Copeptin is a stable cleavage product of the arginine vasopressin precursor and is equimolarly secreted with arginine vasopressin. We aimed to assess whether copeptin is the surrogate marker for complications related chronic liver disease (CLD) such as ascites, hepatic encephalopathy (HE), portosystemic shunts (PSSs), and all causes of mortality in CLD. METHODS: Serum copeptin was measured in 170 CLD patients upon hospital admission. The association of copeptin levels with liver enzymes, liver functional reserve, and clinical parameters was investigated. Cox proportional hazard regression, logistic regression, and Kaplan-Meier analyses were performed to evaluate the associations of copeptin and ascites, HE and PSS formation, and prognostic factors with short-term (1 year) and long-term (4 years) mortality. RESULTS: Serum copeptin levels were significantly correlated with liver and renal function, elevated in parallel with liver disease progression, and also associated with HE. Serum copeptin, albumin-bilirubin score and hepatocellular carcinoma were independent predictors of PSS formation and decreased rate of survival. Serum copeptin and albumin-bilirubin scores were independent predictors of ascites retention. The short-term and long-term cumulative mortality rate was significantly decreased in patients with serum copeptin >5.5 or >4.8 pmol/mL compared with patients in whom serum copeptin levels were <5.5 or <4.8 pmol/mL (P < 0.0001; P < 0.0001). CONCLUSIONS: Serum copeptin level is a predictor for ascites retention and HE and PSS formation associated with portal hypertension. Moreover, serum copeptin level may be useful in predicting the rate of survival in patients with CLD.

Ratio between estimated glomerular filtration rates of creatinine and cystatin C predicts overall survival in patients with hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) patients with sarcopenia have a poor survival, but there are no predictive markers for survival relating to muscle mass and liver function. Therefore, we investigated whether the ratio between estimated glomerular filtration rates of serum creatinine (Scre) and serum cystatin C (Scys) (eGFRcre/eGFRcys) can be used as a predictive marker of survival in HCC patients. METHODS: First, the correlation between Scre/Scys ratio and muscle mass was examined in 50 patients with chronic liver disease. Second, a change in Scre/Scys ratio relating to liver function was investigated in cirrhotic rats. Finally, the relationship between the eGFRcre/eGFRcys ratio and survival was assessed in 86 HCC patients. RESULTS: The Scre/Scys ratio was correlated with skeletal muscle mass index (r = 0.331, P = 0.019) and psoas muscle area index (r = 0.397, P = 0.004) in chronic liver disease patients. In cirrhotic rats, Scre and Scre/Scys ratio were decreased corresponding with liver function. Thirty-five of 86 HCC patients died within the average follow-up period of 35 months. The patients with an eGFRcre/eGFRcys ratio <1.26 had significantly longer rates of survival compared to patients with an eGFRcre/eGFRcys ratio ≥1.26 (28.8 vs. 18.5 months, P = 0.001). Using multivariate Cox regression analyses, the patient-related eGFRcre/eGFRcys ratio (hazard ratio [HR], 4.178; P = 0.007), as well as the tumor-related factors α-fetoprotein (HR, 1.000; P < 0.001) and Barcelona Clinic Liver Cancer stage (HR, 2.589; P < 0.001), were independent predictors of survival. CONCLUSION: The Scre/Scys ratio is associated with muscle mass and liver function. Furthermore, the eGFRcre/eGFRcys ratio could serve as a useful predictive marker for survival of HCC.

Changes in liver function and body composition by direct-acting antiviral therapy for hepatitis C virus infection.

AIM: Management of low skeletal muscle mass (LSM) is a very important topic as LSM affects patient mortality in liver diseases. Changes in body composition are unexplored in chronic hepatitis C virus (HCV) patients, including those with liver cirrhosis, who receive direct-acting antiviral (DAA) therapy. Body composition measurements and liver function tests were carried out before and after DAA therapy. METHODS: Blood examination, visceral fat area (VFA) and extremity skeletal muscle mass were measured using the multifrequency bioelectrical impedance analysis method: (i) at 24 weeks before DAA therapy; (ii) at the start of DAA therapy; (iii) at the end of DAA therapy; (iv) at 24 weeks after DAA therapy; and (v) at 48 weeks after DAA therapy. RESULTS: Serum albumin (Alb) levels were significantly increased at 48 weeks post DAA therapy, especially in patients with LSM. Skeletal muscle mass index (SMI) was significantly increased after DAA therapy (at 24 weeks and 48 weeks post DAA therapy) in patients with LSM (P < 0.05). An increase in SMI was associated with an increase in body weight or a decrease in VFA. CONCLUSIONS: We continuously measured body composition in HCV-infected patients who received DAA therapy and found that skeletal muscle mass was significantly increased, associated with an elevation of serum Alb levels and/or body weight or reduction in VFA, but only in patients who presented with LSM before DAA therapy.

Factors contributing to the development of overt encephalopathy in liver cirrhosis patients.

The aim of this study was to clarify the relationships among psychometric testing results, blood ammonia (NH3) levels, electrolyte abnormalities, and degree of inflammation, and their associations with the development of overt hepatic encephalopathy (HE) in liver cirrhosis (LC) patients. The relationships between covert HE and blood NH3, sodium (Na), and C-reactive protein (CRP) were examined in 40 LC patients. The effects of elevated NH3, hyponatremia, and elevated CRP on the development of overt HE were also investigated. The covert HE group had significantly lower serum Na levels and significantly higher serum CRP levels. During the median observation period of 11 months, 10 patients developed overt HE, and the results of multivariate analysis showed that covert HE and elevated blood NH3 were factors contributing to the development of overt HE. Electrolyte abnormalities and mild inflammation are involved in the pathogenesis of HE. Abnormal psychometric testing results and hyperammonemia are linked to subsequent development of overt HE.

A case of a solitary Mycobacterium avium complex lesion of the liver.

A 70-year-old woman was admitted to our hospital on suspicion of liver tumor on regular abdominal ultrasonography. The abdominal ultrasonography identified a solitary, low-echoic lesion measuring 17mm in diameter in S7. This lesion was not enhanced in any phase of contrast-enhanced computed tomography (CT), and thus we performed a liver biopsy. Histopathological examination revealed a caseating granuloma. The chest CT showed pulmonary nodules, and Mycobacterium intracellulare was cultured from the bronchoalveolar lavage fluid. We diagnosed the individual with a Mycobacterium avium complex infection, and suspected that this was the cause of the solitary liver lesion.

Serum Zinc-α2-glycoprotein Levels Are Associated with the Hepatorenal Function and Predict the Survival in Cases of Chronic Liver Disease.

Objective Zinc-α2-glycoprotein (ZAG) is secreted by various organs, such as liver, kidney and adipose tissue, is involved in lipolysis, and may contribute to the pathogenesis of chronic liver disease (CLD). We therefore assessed whether or not ZAG is a surrogate marker for the hepatorenal function, body composition and all causes of mortality, as well as complications, including ascites, hepatic encephalopathy (HE) and portosystemic shunts (PSS) in CLD. Methods Serum ZAG levels were measured in 180 CLD patients upon hospital admission. The associations of ZAG levels with the liver functional reserve and clinical parameters were investigated using a multiple regression analysis. Kaplan-Meier analyses were performed to evaluate the associations of the ZAG/creatinine ratio (ZAG/Cr) and prognostic factors with mortality. Results High serum ZAG levels were associated with preserving the liver function and renal insufficiency. A multiple regression analysis showed that the estimated glomerular filtration rate (p<0.0001), albumin-bilirubin (ALBI) score (p=0.0018) and subcutaneous fat area (p=0.0023) had a significant independent correlation with serum ZAG levels. Serum ZAG levels were elevated in the absence of HE (p=0.0023) and PSS (p=0.0003). In all patients and those without hepatocellular carcinoma (HCC), the cumulative mortality rate was significantly decreased in patients with a high ZAG/Cr compared with those with a low ZAG/Cr (p=0.0018 and p=0.0002, respectively). The ZAG/Cr, presence of HCC, ALBI score and psoas muscle index were independent predictors of the prognosis in CLD patients. Conclusion Serum ZAG levels are associated with the hepatorenal function and can be used to predict the survival in CLD patients.

Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption.

BACKGROUND/AIMS: Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. We previously reported that pemafibrate significantly improves liver function, serum triglyceride (TG) levels and liver stiffness in non-alcoholic fatty liver disease patients, however the influence of alcohol consumption was not considered. Therefore, we explored pemafibrate efficacy in patients with steatotic liver disease (SLD) and alcohol-associated liver disease (ALD). METHODS: We retrospectively evaluated pemafibrate efficacy on liver enzymes and lipids in metabolic dysfunction-associated SLD (MASLD) (n = 93), MASLD plus increased alcohol intake (MetALD; n = 23) and ALD (n = 22) patients who had taken pemafibrate for at least 48 weeks. Liver shear wave velocity (SWV, n = 75) was also evaluated. RESULTS: In MASLD group, ALT, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and TG values were significantly decreased from baseline to week 24 and week 48 ( P  < 0.0001). ALT and TG values in MetALD group and ALT and AST values in ALD group were also significantly decreased from baseline to week 24 and week 48. Study participant SWV values decreased from baseline to week 48. We observed no significant difference in changes to ALT, AST, γ-GTP and TG (value at week 24 or week 48 minus value at baseline) among the three groups. CONCLUSION: Pemafibrate improves liver function and liver stiffness thus making it a promising therapeutic agent for SLD, even in patients with excess alcohol consumption (MetALD and ALD groups).

Iron overload and glucose abnormalities in chronic hepatitis C virus infection: phlebotomy lowers risk of new-onset diabetes.

BACKGROUND/AIMS: Iron overload and hyperglycemia are common findings in patients with chronic hepatitis C (CHC). The aim of this study was to determine the relation of serum ferritin and hepatic hepcidin expression with glucose metabolic parameters and to evaluate whether long term phlebotomy lowers the risk of new-onset diabetes in CHC patients. METHODOLOGY: Hepatic hepcidin mRNA expression was measured in 28 CHC patients and their relation with clinical parameters and histological findings was evaluated. Ninety-two patients without type 2 diabetes were divided into two groups: a phlebotomy group underwent an initial period of phlebotomy and maintenance phlebotomy was performed; data obtained in CHC patients that declined to receive phlebotomy were used as control. RESULTS: Hepatic hepcidin expression was positively correlated with body mass index and glucose metabolic parameters. A total number of five patients had onset of type 2 diabetes over 38.9 months of follow-up. Long-term phlebotomy tended to lower the risk of new-onset diabetes compared with control CHC patients. In addition, high ferritin levels predicted further episodes of diabetes in control patients. CONCLUSIONS: Iron overload is a risk for the development of diabetes in patients with CHC and that reduction of body iron stores lowers this risk.

Effect of pemafibrate on liver enzymes and shear wave velocity in non-alcoholic fatty liver disease patients.

Background/Aims: Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. Pemafibrate was reported to reduce ALT in non-alcoholic fatty liver disease (NAFLD) patients, but efficacy was not clearly elucidated due to the small size of previous study populations. Therefore, we explored pemafibrate efficacy in NAFLD patients. Methods: We retrospectively evaluated pemafibrate efficacy on liver enzymes (n = 132) and liver shear wave velocity (SWV, n = 51) in NAFLD patients who had taken pemafibrate for at least 24 weeks. Results: Patient ALT levels were decreased from 81.0 IU/L at baseline to 48.0 IU/L at week 24 (P < 0.0001). Serum levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and triglyceride (TG) were significantly decreased, and high-density lipoprotein cholesterol and platelet count were significantly increased, with no change in body weight being observed. Study participant SWV values decreased from 1.45 m/s at baseline to 1.32 m/s at week 48 (P < 0.001). Older age (P = 0.035) and serum TG levels (P = 0.048) were significantly associated with normalized ALT. Changes in AST, ALT, γ-GTP and body weight were significantly correlated with change in SWV. Conclusion: Pemafibrate significantly improves liver function, serum TG and liver stiffness in NAFLD patients. Pemafibrate is a promising therapeutic agent for NAFLD and may be a candidate for NAFLD patients with elevated TG.

Role of Extracellular Vesicles in Absorption and Functional Mechanisms of Quercetin.

SCOPE: Quercetin (QUE), a phytochemical found in various plant foods, has been shown to have a variety of physiological activities in vivo, though biological sites where it has activities and the mechanisms of transport have not been fully elucidated. METHODS AND RESULTS: In the present study, intracellular uptake of QUE into HT-29 human colon adenocarcinoma cells is found to result in spontaneous release of extracellular vesicles (EVs), which are subsequently embedded with QUE. In addition, QUE-embedded EVs are detected in serum of QUE-administered Sprague-Dawley rats. Interestingly, the rate of cellular uptake of QUE-encapsulated EVs (EV-QUE) into RAW264.7 macrophages is markedly higher than that of free QUE. Moreover, EV-QUE suppresses lipopolysaccharide (LPS)-induced nitric oxide at a lower concentration than free QUE. CONCLUSION: The present findings suggest that QUE may be embedded in EVs in the gastrointestinal tract, then become absorbed and enter the bloodstream to exhibit biological activities.

Shoulder function after neck dissection with level IIb preservation: a prospective observational study.

BACKGROUND: Shoulder syndrome can be reduced by preserving the spinal accessory nerve (SAN). However, it is unclear whether performing level IIb preservation will decrease the risk of SAN injury and shoulder syndrome. AIMS/OBJECTIVES: We investigated whether neck dissection with level IIb preservation can reduce shoulder dysfunction and postoperative quality of life (QOL) in head and neck cancer patients. MATERIAL AND METHODS: This prospective observational study enrolled patients who underwent neck dissection from 2011 to 2014. Patients were divided into three groups (level IIb preservation group [group 1], IIb dissection group [group 2], and IIb and V dissection group [group 3]). Postoperative shoulder function and QOL were evaluated among the three groups. RESULTS: There were a total of 35 neck sides in three groups, with nine neck sides in group 1, 16 neck sides in group 2, and 10 neck sides in group 3. Although the results showed less shoulder dysfunction in group 1 at early postoperative period. The QOL in group 1 was preserved in the early postoperative period. CONCLUSIONS AND SIGNIFICANCE: Neck dissection with level IIb preservation may help reduce shoulder syndrome and maintain QOL in the early postoperative period.

Hepatocellular Carcinoma Pseudoprogression Involving the Main Portal Vein, Right Ventricular Invasion, and Exacerbation of Lung Metastases in a Patient on Atezolizumab Plus Bevacizumab.

A 70-year-old man was diagnosed with hepatocellular carcinoma (HCC) with portal vein invasion and lung metastases, for which atezolizumab plus bevacizumab (ATZ/BEV) was initiated. After two months, computed tomography revealed tumor growth accompanied by ascites, right ventricular invasion, exacerbation of the lung metastases, and main portal vein invasion. However, continuation of ATZ/BEV caused remarkable size reductions in all lesions, finally resulting in the disappearance of the vascular invasion and lung metastases after nine cycles of treatment. The tumor growth was considered to reflect pseudoprogression, which is difficult to distinguish from hyperprogression. We herein report a remarkable HCC case of pseudoprogression on ATZ/BEV.

Recurrent hepatocellular carcinoma with osteoclast-like giant cells: a case report.

BACKGROUND: Hepatocellular carcinoma with osteoclast-like giant cells is very rare and has an extremely poor prognosis. Here, we report a case of hepatocellular carcinoma with osteoclast-like giant cells that had a relatively better prognosis. CASE PRESENTATION: A 70-year-old Japanese man with hepatitis B virus-related liver cirrhosis was admitted to our hospital for the treatment of recurrent hepatocellular carcinoma. At the age of 60 years, he was first diagnosed as having hepatocellular carcinoma in the right lobe (9 cm in diameter), and liver resection of segment 7/8 was performed. Histological findings showed well-differentiated hepatocellular carcinoma. Since then, imaging studies have been performed every 3 or 4 months. One year later, hepatocellular carcinoma recurred in the lateral segment, and radiofrequency ablation was performed. Nine years after the first presentation, hepatocellular carcinoma recurrences were detected in the caudate lobe and segment 5 by imaging studies. Surgical resection of the caudate lobe was performed, and ultrasonography-guided radiofrequency ablation was subsequently performed for the segment 5 tumor. The resected tumor was simple nodular, well-differentiated HCC; it measured 21 × 21 mm and contained many osteoclast-like giant cells. As neither vascular nor bile duct invasion was found, we believe that radical resection was achieved. Since then, the hepatocellular carcinoma has not recurred for over a year and a half. CONCLUSION: Hepatocellular carcinoma with osteoclast-like giant cells is very rare and the prognosis is extremely poor, but early detection can lead to a better clinical course.

Complement complex 1 subunit q-mediated hepatic stellate cell activation with connective tissue growth factor elevation is a prognostic factor for survival in rat and human chronic liver diseases.

Complement complex 1 subunit q (C1q) has multiple functions, including cell migration, in addition to its traditional complement-activating effect. Research shows C1q is a ligand for frizzled receptors (FZDs). FZD-induced yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) alternate Wnt signaling activation induces connective tissue growth factor (CTGF) production and hepatic stellate cell (HSC) activation. However, no study exists in which C1q directly induces CTGF in HSCs. Here, we investigated the role of C1q in HSC activation. Human HSCs (LX2) were incubated with C1q to assess HSC activation. C1q and fibrotic markers were assessed using immunohistochemistry, immunoblotting, and quantitative reverse-transcription polymerase chain reaction in cirrhotic rats administered CCl4 for 21 weeks. Serum C1q, liver function, and fibrosis score were measured in 91 patients with chronic liver disease. The correlations between serum C1q and liver function, fibrosis score, and survival prognosis were examined. C1q-activated LX2s showed morphologic changes, up-regulation of CTGF, tissue inhibitors of metalloproteinases (TIMP-1), and alternate Wnt signal genes FZD2, TAZ, and cysteine-rich angiogenic inducer 61 (Cyr61). Cirrhotic rat liver C1q expression correlated with the Azan-positive area and expression of CTGF, TIMP-1, hyaluronan synthase (HAS)1, HAS3, and CD44. Expression of C1q protein and C1q, CTGF, and TIMP-1 genes were higher in deceased cirrhotic rat livers compared to surviving rats. Human serum C1q levels increased in liver cirrhosis compared to chronic hepatitis and correlated with liver fibrosis and functional markers. Ten patients suffered liver-related death over a 66-month observation period. The C1q cut-off value (11 mg/dl) showed patients with serum values < 11 mg/dl had longer rates of survival compared to C1q ≥ 11 mg/dl. Conclusion: C1q-mediated HSC activation in liver fibrosis is associated with CTGF elevation. Additionally, serum C1q may be diagnostic for survival in human chronic liver diseases.

Association of lithocholic acid with skeletal muscle hypertrophy through TGR5-IGF-1 and skeletal muscle mass in cultured mouse myotubes, chronic liver disease rats and humans.

Background: Hepatic sarcopenia is one of many complications associated with chronic liver disease (CLD) and has a high mortality rate; however, the liver-muscle axis is not fully understood. Therefore, few effective treatments exist for hepatic sarcopenia, the best of which being branched-chain amino acid (BCAA) supplementation to help increase muscle mass. Our aim was to investigate the molecular mechanism(s) of hepatic sarcopenia focused on bile acid (BA) composition. Methods: The correlation between serum BA levels and psoas muscle mass index (PMI) was examined in 73 CLD patients. Gastrocnemius muscle phenotype and serum BA levels were assessed in CLD rats treated with BCAA. Mouse skeletal muscle cells (C2C12) were incubated with lithocholic acid (LCA), G-protein-coupled receptor 5 (TGR5) agonist or TGR5 antagonist to assess skeletal muscle hypertrophy. Results: In human CLD, serum LCA levels were the sole factor positively correlated with PMI and were significantly decreased in both the low muscle mass group and the deceased group. Serum LCA levels were also shown to predict patient survival. Gastrocnemius muscle weight significantly increased in CLD rats treated with BCAA via suppression of protein degradation pathways, coupled with a significant increase in serum LCA levels. LCA treated C2C12 hypertrophy occurred in a concentration-dependent manner linked with TGR5-Akt pathways based upon inhibition results via a TGR5 antagonist. Conclusions: Our results indicate LCA-mediated skeletal muscle hypertrophy via activation of TGR5-IGF1-Akt signaling pathways. In addition, serum LCA levels were associated with skeletal muscle mass in cirrhotic rats, as well as CLD patients, and predicted overall patient survival. Funding: This research was supported by JSPS KAKENHI Grant Number 22K08011 and 21H02892, and AMED under Grant Number JP21fk0210090 and JP22fk0210115. Maintaining cirrhotic rats were partially supported by Otsuka Pharmaceutical Company.

The prognostic role of controlling nutritional status and skeletal muscle mass in patients with hepatocellular carcinoma after curative treatment.

BACKGROUND: Nutritional status and skeletal muscle mass affect the prognosis of hepatocellular carcinoma (HCC). Nutritional status is closely associated with skeletal muscle mass. Here, we investigate the effect of controlling preoperative nutritional status and skeletal muscle mass on the prognosis of HCC after curative treatment. METHODS: This retrospective analysis contained 181 patients who received curative treatment of HCC including liver resection or radiofrequency ablation (RFA) therapy. Nutritional status and skeletal muscle mass were evaluated prior to therapy using the controlling nutritional status (CONUT) score and psoas muscle mass index (PMI), respectively. Associations of predictor variables with overall survival (OS) and progression-free survival (PFS) were determined using Cox proportional hazards regression and CHAID decision tree algorithm analysis. RESULTS: A total of 111 patients (61.3%) were determined to be of poor nutritional status and 100 patients (55.2%) had muscle mass depletion. Patients with PS 0, Barcelona clinic liver cancer (BCLC) stage 0, low CONUT score, and high PMI showed significantly better OS than those with PS 1, BCLC stage A, high CONUT score, and low PMI. Multivariate analysis indicated that a high CONUT score [hazard ratio (HR) 4.130; 95% confidence interval (CI), 1.713-9.958; P < 0.01) and low PMI (HR 4.625; 95% CI, 1.704-12.549; P < 0.01) found to be useful for predicting OS in patients after curative treatment of HCC. Regarding PFS, a significant predictor was only tumor numbers in univariate analysis (HR 2.147; 95% CI, 1.350-3.414; P = 0.001). In decision tree analysis, the mortality rate was 28.8%, 12.5%, and 1.9% in patients with a high CONUT score, with a low CONUT score-low PMI, or with a low CONUT score-high PMI, respectively. CONCLUSION: The combined CONUT score and PMI were found to be independent predictors of OS in HCC patients after liver resection or RFA.

Do heel-unloading orthoses improve clinical outcomes in patients after surgical treatment of calcaneal fracture? A propensity-matched, multicenter analysis of the TRON database.

BACKGROUND: Postoperative protocols after surgical treatment of calcaneal fracture have not been standardized to date. There are only a few reports on the efficacy of heel-unloading orthoses (HUOs; Mars shoe, Graffin orthosis), and thier efficacy is uncertain. OBJECTIVES: The purpose of this study was to compare postoperative radiologic and clinical outcomes in patients with calcaneal fractures who used Graffin orthosis. STUDY DESIGN: Multicenter retrospective study. METHODS: We finally extracted 182 patients from a database of the Trauma Research Group of Nagoya and divided them into two groups: group C (underwent casting or splinting only) and group O (Graffin orthosis was used). A propensity score algorithm was used to match group C to group O in a 1:1 ratio. We evaluated American Orthopaedic Foot and Ankle Society (AOFAS) score at three and six months after surgery and at final follow-up. Differences in reduction of the Böhler angle between the two groups were evaluated radiographically. All data were analyzed with a t-test or Fisher's exact test. P < .05 was considered statistically significant. RESULTS: The AOFAS score 3 months after surgery in group O was significantly higher than that in group C (69.57 vs. 77.22; P = .004). However, there were no statistically significant differences between group C vs. group O in AOFAS scores at 6 months after surgery and at final follow-up (81.92 vs. 85.67 and 89.18 vs. 88.13; P = .087 and 0.597, respectively). There was no significant statistical difference in the reduction of the Böhler angle (5.07 vs. 5.89; P = .529). CONCLUSIONS: At 3 months postoperatively, the orthosis group showed predominantly better functional results. We believe that heel-unloading orthoses are useful for patients who require an early return to work and to daily life.