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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.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.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 lt; 0.01) and low PMI (HR 4.625; 95% CI, 1.704-12.549; P lt; 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.The combined CONUT score and PMI were found to be independent predictors of OS in HCC patients after liver resection or RFA.

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.The purpose of this study was to compare postoperative radiologic and clinical outcomes in patients with calcaneal fractures who used Graffin orthosis.Multicenter retrospective study.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.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).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.

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.

We investigated the IgE reactivity to crude and purified milk antigens in the sera of 112 dogs with cutaneous adverse food reactions (CAFRs). Of the 112 dogs, 33 (29%) had specific IgE for crude milk antigens. In the dogs with milk-specific IgE, IgE reactivity to casein, bovine serum albumin (BSA), α-lactalbumin, β-lactoglobulin, and bovine IgG were 81%, 85%, 39%, 27%, and 35%, respectively. Casein and BSA may be important allergens in dogs with CAFRs. Some canine vaccines contain casein hydrolysate as a stabilizer and the pooled serum with anti-casein IgE showed IgE reactivity to the vaccines containing it. Information about IgE reactivity to casein in dogs with CAFRs could be useful for predicting adverse reactions to the vaccines including casein hydrolysate.

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.

[Background & aims] 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-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] 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. The correlation between serum BA levels and psoas muscle area index (PMI) was examined in 73 CLD patients. [Results] 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. 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. [Conclusion] 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.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease that causes a decline of kidney function that progresses in relation to the enlargement of kidney cysts.1 Tolvaptan, a selective vasopressin V2-receptor antagonist, suppresses the production of cAMP, which is expected to be beneficial for suppressing the growth of renal cysts in patients with ADPKD.2 The effectiveness of tolvaptan was demonstrated in a phase III international clinical trial (TEMPO 3:4 trial)3 and its use is recommended in the guidelines.4 Elevation of liver enzymes was reported in 4.9% of patients who received tolvaptan in the TEMPO 3:4 trial.3 Eight of 135 Japanese patients in the TEMPO 3:4 trial had a more than 3-fold increase above the upper limit of normal (ULN) in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels; however, these levels recovered after the discontinuation of tolvaptan.5 Thus far, tolvaptan-associated liver enzyme elevation has recovered after cessation or dose reduction, and no cases of tolvaptan-associated severe liver failure have been reported. We herein report a patient with ADPKD who underwent liver transplantation for tolvaptan-associated acute liver failure.

Manipulation of the omni-directional mobile robot is more complicated when compared with the manipulation of a general mobile robot which is controlled by two degrees of freedom. By the reason that the manipulation of the omni-directional mobile robot is required three degrees of freedom controlling, we have developed a new control device for this mobile robot which can be operated by a human’s foot via the spherical pedal control device, not by hands. Through operating the spherical pedal or a new control device, operators can use their hands for another task. At this point, by rotating the spherical pedal control device in each axis direction is possible to control the robot’s three degrees of freedom motion, the velocity vector, and the angular velocity around its body.

Diagnosing sarcopenia is challenging. This multicenter cross-sectional study aimed to evaluate the utility of the SARC-F score system for identifying sarcopenia in patients with chronic liver disease (CLD). We enrolled 717 patients from five participating centers who completed the SARC-F between November 2019 and March 2021. Sarcopenia was diagnosed based on the Japan Society of Hepatology Working Group on Sarcopenia in Liver Disease Consensus. Muscle strength was estimated using a grip dynamometer, and muscle mass was assessed using computed tomography or bioelectrical impedance analysis. The association between SARC-F and sarcopenia was analyzed using a logistic regression model. The optimal SARC-F cutoff value for identifying sarcopenia was determined using receiver operating characteristic (ROC) curve analysis. Of the 676 eligible patients, 15% were diagnosed with sarcopenia. The SARC-F distribution was 0 points in 63% of patients, 1 point in 17%, 2 points in 7%, 3 points in 4%, and ≥4 points in 8%. The SARC-F items of “Strength” (odds ratio (OR), 1.98, 95% confidence interval (CI), 1.03–3.80) and “Falls” (OR, 2.44, 95% CI, 1.48–4.03) were significantly associated with sarcopenia. The SARC-F value of 1 point showed a higher discriminative ability for identifying sarcopenia than the 4 points that are conventionally used (p &lt, 0.001), with an area under the ROC curve of 0.68, sensitivity of 0.65, specificity of 0.68, positive predictive value of 0.27, and negative predictive value of 0.92. SARC-F is useful for identifying patients with CLD who are at risk of sarcopenia.

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). 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. 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). For calcaneal fracture, STS provides similar fixation effectiveness and functional outcomes as LEP while reducing the likelihood of infection.

The first twenty years of operation of gravitational-wave interferometers have shown that these detectors are affected by physical disturbances from the surrounding environment. These are seismic, acoustic, or electromagnetic disturbances that are mainly produced by the experiment infrastructure itself. Ambient noise can limit the interferometer sensitivity or potentially generate transients of non-astrophysical origin. Between 1 April 2019 and 27 March 2020, the network of second generation interferometers&mdash, LIGO, Virgo and GEO&mdash, performed the third joined observing run, named O3, searching for gravitational signals from the deep universe. A thorough investigation has been done on each detector before and during data taking in order to optimize its sensitivity and duty cycle. In this paper, we first revisit typical sources of environmental noise and their coupling paths, and we then describe investigation methods and tools. Finally, we illustrate applications of these methods in the hunt for environmental noise at the Virgo interferometer during the O3 run and its preparation phase. In particular, we highlight investigation techniques that might be useful for the next observing runs and the future generation of terrestrial interferometers.

Membrane vesicles (MVs) play biologically important roles in Gram-positive bacteria, and purification is essential for their study. Although high-performance flow cytometry has the capability to quantify and isolate specific small particles, it has not been examined for MV isolation. In this study, we used high-performance flow cytometry to analyze MV from Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, prepared by iodixanol density-gradient ultracentrifugation. Analysis of the quality of MV samples before and after sorting showed that the flow cytometric sorting provided higher purity and uniformity compared to gradient isolation alone. The MV purification method using flow cytometry should prove useful for applications requiring a very high purity of MV samples such as proteomic, metagenomic or lipidomic studies.

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

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

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

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end-stage liver disease and Child-Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase-associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme-linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real-time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll-like receptor 4, and interleukin-6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow-up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946-956).

To introduce phage therapy against multidrug-resistant Staphylococcus aureus in Western medicine, the establishment of phage manufacturing, particularly phage propagation, is indispensable. For the propagation of S. aureus phages, knowledge of the effects of phage types, process parameters, and analytical methodologies should be investigated. In this study, S. aureus phage propagations were studied in a flask with a new class of design of experiments, definitive screening design, using S. aureus phages S13' and S25-3 in different taxonomies. Four process parameters, namely, multiplicity of infection, bacterial density at infection, time of harvest, and temperature, were evaluated with the regression models based on the phage concentration data measured using plaque assay and quantitative polymerase chain reaction. As a result, phage propagations measured using plaque assay and quantitative polymerase chain reaction were overall similar to each other in the case of phage S13', while they differed in the case of phage S25-3. These results suggest that the propagation processes need to be developed according to phage type, and the choice of methodologies for phage concentration measurements should be carefully considered.

Objective Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, dyslipidemia and type-2 diabetes mellitus. Bile acids (BAs) bind to the farnesoid X receptor (FXR) and G protein-coupled receptor 5 (TGR5), which are involved in lipid and glucose metabolism and energy expenditure. The present study aimed to determine associations between the circulating BAs and the skeletal muscle volume (SMV), and lipid and glucose metabolism in patients with NAFLD. Methods Serum BAs and metabolic parameters were measured in 55 patients with NAFLD (median age, 55 years). The changes (Δ) in serum BA (ΔBA) and metabolic parameters were determined in 17 patients (male, n=10; female, n=7) who received nutritional counseling for 12 months. Results Spearman's test revealed that the levels of 12α-hydroxysterol (12α-OH) BAs, including deoxycholic acid (DCA), were inversely correlated with the SMV of the upper and lower limbs and the total SMV. A multivariate analysis revealed that the level of DCA was correlated with a reduced total SMV, whereas non-12α-OH BAs, including chenodeoxycholic acid (CDCA), were correlated with an increased SMV of the lower limbs. Changes in CDCA were positively correlated with the ΔSMV of the lower limbs, and inversely correlated with the Δwaist-hip ratio and Δtotal cholesterol. Changes in the total non-12α-OH BA level were positively correlated with the ΔSMV of the lower limbs. Conclusion Circulating BAs were associated with SMV. The 12α-OH BAs, including DCA were associated with reduced SMV levels, whereas non-12α-OH BAs including CDCA were associated with increased SMV levels. The molecular mechanisms underlying the association between the BA levels and the SMV remain to be explored.

Background Denosumab (DMB) is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, increasing bone density and reducing fracture risk. Also DMB is a useful therapeutic agent for both rheumatoid arthritis (RA-OP) and primary osteoporosis (P-OP). However there is still few comparative study of clinical efficacy of DMB between RA-OP and P-OP. Objectives To compare the clinical efficacy of DMB in patients with osteoporosis between rheumatoid arthritis and primary osteoporosis for 24 months. Methods RA patients diagnosed according to the 2010 ACR/EULAR criteria. RA-OP and P-OP patients met at least one of the following criteria were eligible; a bone mineral density T score of -2,5 or less at the lumber spine or total hip and either one or more moderate or severe vertebral fractures or two or more mild vertebral fractures. All patients were initiated DMB from between October, 2013 and August, 2016. The final study cohort of 61 RA- OP and 50 P-OP patients received continuous DMB therapy more than 24 months. The DMB dose was 60mg at once every 6 months. In all cases native or activated vitamin D has been used. We reviewed the results for 24 months about the increase and decrease of bone mineral density(BMD) of lumbar spine(LS) and total hip(TH) by DEXA and bone turnover markers, intact n-terminal propeptide type I procollagen(PINP) and tartrate-resistant acid phopshatate form 5b(TRACP-5b). Results In the patients of RA-OP (n=61) and P-OP (n=50), the number of female was each 56(92%) and 45(90%) cases(p=0.741). The mean age was 72.7 ± 7.5 and 76.8 ± 7.8 years old (p=0.006); disease duration of RA-OP patients was 12.6 ± 12.9 years; the body mass index was 20.4 ± 2.7 and 20.3± 3.0 (p=0.687) and the FRAX was 27.2 ± 15.7 and 24.6 ± 11.1 (p=0.745). Clinical findings related to RA-OP at baseline were as follows; CRP 0.8 ± 1.1; DAS-CRP 3.28 ± 1.36; HAQ 1.16 ± 1.04 in RA-OP patients and in the patients of RA-OP and P-OP, bone turnover markers and bone mineral density at baseline were as follows; P1NP 57.7 ± 32.2 and 64.0 ± 32.7 μg/l(p=0.151); TRACP-5b 563 ± 237 and 570 ± 217 mU/dL (p=0.674); LS-BMD 0.85 ± 0.16 and 0.74 ± 0.13 g/cm2(p Conclusion DMB was effective for both RA-OP and P-OP, and the clinical efficacy was almost similar between the two groups. Disclosure of Interests None declared

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.

Background:Romosozumab (ROM), a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. And although it is a novel therapeutic agent for osteoporosis, which has shown high effects of increasing bone density and inhibiting fragile fracture in overseas clinical trials. However the clinical efficacy in daily clinical practice is unknown.Objectives:To evaluate the early clinical efficacy of ROM in patients with osteoporosis between rheumatoid arthritis (RA-OP) and primary osteoporosis (P-OP) for 6 months.Methods:RA patients diagnosed according to the 2010 ACR/EULAR criteria. RA-OP and P-OP patients met at least one of the following criteria were eligible; a bone mineral density T score of -2,5 or less at the lumber spine or total hip and either one or more moderate or severe vertebral fractures or two or more mild vertebral fractures. All patients were initiated ROM from between March and June, 2019. The total number of patients was 15 cases, including 8 RA-OP and 7 P-OP. All patients received continuous ROM therapy more than 6 months. The DMB dose was 210mg at once every 1 months. In all cases native or activated vitamin D has been used. We reviewed the results for 6 months about the increase and decrease of bone mineral density (BMD) of lumbar spine(LS) and total hip(TH) by DEXA and bone turnover markers, intact n-terminal propeptide type I procollagen(PINP) and tartrate-resistant acid phopshatate form 5b(TRACP-5b).Results:The gender was all female. The mean age was 71.8 ± 8.7; disease duration of RA-OP patients was 23.0 ± 15.1 years; the body mass index was 19.9 ± 3.2 and the FRAX was 32.5 ± 14.9. Clinical findings related to RA-OP at baseline were as follows; CRP 0.97 ± 0.77; DAS-CRP 3.22 ± 0.41; HAQ 1.41 ± 0.94 in RA-OP patients and in the all patients, bone turnover markers and bone mineral density at baseline were as follows; P1NP 72.2 ± 39.8; TRACP-5b 539 ± 212; LS-BMD and T-score 0.80 ± 0.20 g/cm2and -2.75 ± 1.36 and TH-BMD 0.55 ± 0.07 g/cm2and -3.18 ± 0.55 g/cm2. The rate of increased P1NP from baseline to 1, 3 and 6 months were each -96.8 ± 80.8% at 1 month, 106.8 ± 115.6% at 3 month and 90.7 ± 115.7% at 6 month and decreased TRAC-5b were -20.4 ± 20.6% at 1 month, -80.8 ± 19.6% at 3 month and -1.8 ± 50.8% at 6 month. The rate of increased LS-BMD from baseline to 6 months were 11.0 ± 8.0% and TH-BMD were 5.3 ± 3.8% (Fig. 1, 2).Conclusion:Early clinical efficacy of ROM for RA-OP and P-OP was extremely effective and has the high potential to be an important option in the treatment of osteoporosis.Disclosure of Interests:None declared

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.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.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.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.

Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (L-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine+BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine+BCAA and BCAA-alone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb.

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.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.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.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.

Aims: Chronic hepatitis C virus (HCV) infection is often associated with glucose metabolic disorders and iron overload. It has recently been shown that reactive oxygen species (ROS) increase gluconeogenesis in hepatocytes through the forkhead box-containing protein O subfamily-1 (FOXO1)-dependent pathway. The aim of this study is proving a cause-and-effect relationship between iron-mediated ROS production and insulin resistance (IR) in chronic hepatitis C (CH-C) patients. Methods: The study included 42 patients with CH-C (22 males and 20 females, median age 53 years). Homeostasis model assessment of insulin resistance (HOMA-IR) value was assessed for each patient at entry. Gene expression levels in the biopsied liver tissues were determined by quantitative reverse transcription-polymerase chain reaction (RT- PCR). In addition, the effect of ROS on gluconeogenesis was assessed using HepG2 cells treated with a well-known ROS generator, diethylmaleate (DEM). Results: The serum ferritin levels were significantly correlated with the serum aspartate aminotransferase level, alanine aminotransferase level, HOMA-IR value, grade of fatty accumulation, total hepatic iron score, and 8-OH-deoxy-2’-guanosine (8-OHdG)-positive cell count. FOXO1 expression was correlated with 8-OHdG-positive cell count, phosphoenolpyruvate carboxykinase (PEPCK) expression, and HOMA-IR. In HepG2 cells, the gene transcription of FOXO1 and PEPCK was increased by DEM treatment, which was associated with an increase in non-phosphorylated FOXO1 protein in the nuclear fraction. Conclusions: Iron-mediated ROS production enhances gluconeogenesis through the FOXO1-mediated pathway and is an affecting factor to IR in patients with CH-C.

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.

Objective Although the prognosis is known to be poor in cirrhosis patients associated with sarcopenia, the relationships among skeletal muscle, visceral fat, and the liver have not yet been thoroughly investigated. Therefore, the prognosis and its associations with body composition and the severity of liver disease were examined in patients with cirrhosis. Methods The skeletal muscle mass and visceral fat area were measured in 161 patients with cirrhosis, the effects of body composition on the prognosis were analyzed, and any factors that contribute to changes in body composition were assessed. Results During the mean observation period of 1,005 days, 73 patients died. Patients with sarcopenia or sarcopenic obesity had a poor prognosis, and this difference was pronounced in the subset of patients classified as Child-Pugh class A. A decreased skeletal muscle mass was strongly correlated with decreased serum albumin levels. Sarcopenia is a common feature of advanced cirrhosis, and transitions were observed from normal body composition to sarcopenia and from obese to sarcopenic obesity. Conclusion The body composition is a prognostic factor for cirrhosis, and a better body composition may be advantageous for obtaining a long-term survival in patients with cirrhosis.

はじめに：中咽頭癌は亜部位により異なる放射線感受性を示すことが知られており，腫瘍の存在部位により異なる治療指針が求められるが，本邦ではその治療指針について厳密には規定されていない。本報告では，2000年3月から2009年3月までに当科で初回治療を行った中咽頭扁平上皮癌99例の治療成績をもとに，中咽頭癌の亜部位別の治療指針につき検討した。方法：全症例につき5年全生存率（Overall Survival：OS），5年死因特異的生存率（Cause-specific survival：CSS）を，Kaplan-Meier生存曲線を用いてretrospectiveに検討した。また，Stage I，II群とStage III，IV群の5年CSSを検討した。初回治療別に手術群と放射線，化学療法ないし放射線化学療法を行った群（放射線，化学療法群）に分類し，各群の5年CSSを検討した。さらに亜部位別に，側壁型，上壁型はStage I，IIとStage III，IVの各群について初回治療別の5年CSSを検討した。前壁型および後壁型は初回治療別の5年CSSを検討した。結果：全症例での5年OSは50%，5年CSSは59%であった。Stage I，II群と比較してStage III，IV群は有意に予後不良であった。初回治療別では手術群は33例，放射線，化学療法群は66例で，5年CSSはそれぞれ76%，52%であった。側壁型Stage I，II群の5年CSSは90%で，初回治療別にみると手術群100%，放射線，化学療法群83%だった。側壁型Stage III，IV群の5年CSSは63%で，初回治療別には手術群87%，放射線，化学療法群55%だった。上壁型Stage I，II群の5年CSSは85%で，初回治療別にみると手術群100%，放射線，化学療法群66%だった。上壁型Stage III，IV群の5年CSSは50%で，初回治療別には手術群75%に対して，放射線，化学療法群では5年生存率が得られなかった。前壁型，後壁型は初回治療の別に関わらず，5年観察できた例がなかった。まとめ：側壁型，上壁型の手術群の予後は良好であり，手術症例の選択は妥当であったと考えられる。主に側壁型で，より低侵襲な口内法切除の適応拡大が今後の検討課題の一つである。一方で，放射線・化学療法群の治療成績に課題があり，併用化学療法のレジメンの変更やNACの導入が治療成績の向上に必要と考えられる。