Evaluation of target area under the concentration-time curve of vancomycin in an initial dosing design: a retrospective cohort study.

OBJECTIVES: Area under the concentration-time curve (AUC)-guided dosing of vancomycin was introduced in a clinical setting; however, the target range of non-steady-state AUCs, such as Day 1 AUC and Day 2 AUC, remains controversial. Therefore, we sought to determine pharmacokinetic parameter thresholds and identify independent risk factors associated with acute kidney injury (AKI) to establish a safe initial dosing design for vancomycin administration. METHODS: A single-centre, retrospective, cohort study of hospitalized patients treated with vancomycin was conducted to determine the threshold of both non-steady-state AUCs (Day 1 and 2 AUCs) and trough levels at the first blood sampling point (therapeutic drug monitoring, TDM). In addition, independent risk factors associated with AKI were evaluated using univariate and multivariate logistic regression analyses. RESULTS: The thresholds for predicting AKI were estimated as 456.6 mg·h/L for AUC0-24h, 554.8 mg·h/L for AUC24-48h, 1080.8 mg·h/L for AUC0-48h and 14.0 µg/mL for measured trough levels, respectively. In a multivariate analysis, Day 2 AUC ≥ 554.8 mg·h/L [adjusted odds ratio (OR), 57.16; 95% confidence interval (CI), 11.95-504.05], piperacillin/tazobactam (adjusted OR, 15.84; 95% CI, 2.73-127.70) and diuretics (adjusted OR, 4.72; 95% CI, 1.13-21.01) were identified as risk factors for AKI. CONCLUSIONS: We identified thresholds for both AUCs in the non-steady-state and trough levels at the first TDM. Our results highlight the importance of monitoring not only the AUC but also trough levels during vancomycin treatment to reduce the likelihood of AKI.

Development and Evaluation of a Novel Software Program, SAKURA-TDM, for Area Under the Concentration-Time Curve-Guided Vancomycin Dosing: A Short Communication.

BACKGROUND: The area under the concentration-time curve (AUC)-guided dosing of vancomycin has been introduced in Japan; however, the optimal dosing method remains controversial. Here, a novel software program was developed for AUC-guided vancomycin dosing and to estimate the theoretical threshold of the steady-state AUC 24 that could reduce the risk of renal injury. METHODS: A single-center, retrospective, observational study was conducted to develop a novel software program (SAKURA-TDM ver.1.0) for AUC-guided dosing. The estimation accuracy of pharmacokinetic parameters determined using SAKURA-TDM was compared with that of clinically available software programs and assessed with Bland-Altman analysis. In addition, theoretical cutoff points of the steady-state AUC 24 and the predicted trough values were estimated using Youden J statistic approach. RESULTS: The estimation accuracy of pharmacokinetic parameters and AUC determined using SAKURA-TDM was comparable to that of other TDM software programs. Of note, despite a good relationship between the predicted AUC 24 and trough values, the correlation between the predicted AUC 24 and measured trough values was not strong. The cutoff values of the steady-state AUC 24 and the predicted trough value for reducing the probability of a measured trough value of >20 mcg/mL were 513.1 mg·h/L and 15.6 mcg/mL, respectively. CONCLUSIONS: We demonstrated the equivalence of the estimated PK parameters between SAKURA-TDM and other TDM software programs available in Japan. Considering the threshold of both trough values and the steady-state AUC and monitoring of the AUC in a non-steady state, it would be possible to reduce the risk of vancomycin-associated renal injury.

Optimal allocation of physicians improves accessibility and workload disparities in stroke care.

BACKGROUND: Inequalities in access to stroke care and the workload of physicians have been a challenge in recent times. This may be resolved by allocating physicians suitable for the expected demand. Therefore, this study analyzes whether reallocation using an optimization model reduces disparities in spatial access to healthcare and excessive workload. METHODS: This study targeted neuroendovascular specialists and primary stroke centers in Japan and employed an optimization model for reallocating neuroendovascular specialists to reduce the disparity in spatial accessibility to stroke treatment and workload for neuroendovascular specialists in Japan. A two-step floating catchment area method and an inverted two-step floating catchment area method were used to estimate the spatial accessibility and workload of neuroendovascular specialists as a potential crowdedness index. Quadratic programming has been proposed for the reallocation of neuroendovascular specialists. RESULTS: The reallocation of neuroendovascular specialists reduced the disparity in spatial accessibility and the potential crowdedness index. The standard deviation (SD) of the demand-weighted spatial accessibility index improved from 125.625 to 97.625. Simultaneously, the weighted median spatial accessibility index increased from 2.811 to 3.929. Additionally, the SD of the potential crowdedness index for estimating workload disparity decreased from 10,040.36 to 5934.275 after optimization. The sensitivity analysis also showed a similar trend of reducing disparities. CONCLUSIONS: The reallocation of neuroendovascular specialists reduced regional disparities in spatial accessibility to healthcare, potential crowdedness index, and disparities between facilities. Our findings contribute to planning health policies to realize equity throughout the healthcare system.

High preoperative serum strontium levels increase the risk of acute kidney injury after cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgeries. The incidence of AKI after cardiac surgeries using cardiopulmonary bypass (CPB-AKI) is high, emphasizing the need to determine strategies to prevent CPB-AKI. This study investigates the correlation between CPB-AKI and trace metal levels in clinical and animal studies. METHODS: Samples and clinical data were obtained from 74 patients from the Nagoya City University Hospital and Okazaki City Hospital. Blood samples were collected before, immediately after, and 2 h after CPB withdrawal. Trace metal levels were measured using inductively coupled plasma mass spectrometry. Sr or vehicle treatment was orally administered to the rats to determine if Sr was associated with CPB-AKI. After the treatment, ischemia-reperfusion (IR) injury was induced, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. RESULTS: In this clinical study, the incidence of CPB-AKI was found to be 28% (21/74). The body mass index and estimated glomerular filtration rate were significantly different in patients with AKI. The intensive care unit and hospital stay were longer in AKI patients than in non-AKI patients. The Na, Fe, and Sr levels were significantly higher in AKI patients before CPB. Also, Fe and Sr were higher immediately after CPB withdrawal, and Sr was higher 2 h after CPB withdrawal in AKI patients. Animal studies showed that Sr-treated rats had significantly increased SCr and BUN levels than vehicle-treated rats at 24 h post-IR injury. CONCLUSIONS: High preoperative serum Sr levels may be associated with CPB-AKI.

Spatial-temporal analysis of cerebral infarction mortality in Hokkaido, Japan: an ecological study using a conditional autoregressive model.

BACKGROUND: Accessibility to stroke treatments is a challenge that depends on the place of residence. However, recent advances in medical technology have improved health outcomes. Nevertheless, the geographic heterogeneity of medical resources may increase regional disparities. Therefore, evaluating spatial and temporal influences of the medical system on regional outcomes and advanced treatment of cerebral infarction are important from a health policy perspective. This spatial and temporal study aims to identify factors associated with mortality and to clarify regional disparities in cerebral infarction mortality at municipality level. METHODS: This ecological study used public data between 2010 and 2020 from municipalities in Hokkaido, Japan. We applied spatial and temporal condition autoregression analysis in a Bayesian setting, with inference based on the Markov chain Monte Carlo simulation. The response variable was the number of deaths due to cerebral infarction (ICD-10 code: I63). The explanatory variables were healthcare accessibility and socioeconomic status. RESULTS: The large number of emergency hospitals per 10,000 people (relative risk (RR) = 0.906, credible interval (Cr) = 0.861 to 0.954) was associated with low mortality. On the other hand, the large number of general hospitals per 10,000 people (RR = 1.123, Cr = 1.068 to 1.178) and longer distance to primary stroke centers (RR = 1.064, Cr = 1.014 to 1.110) were associated with high mortality. The standardized mortality ratio decreased from 2010 to 2020 in Hokkaido by approximately 44%. Regional disparity in mortality remained at the same level from 2010 to 2015, after which it narrowed by approximately 5% to 2020. After mapping, we identified municipalities with high mortality rates that emerged in Hokkaido's central and northeastern parts. CONCLUSION: Cerebral infarction mortality rates and the disparity in Hokkaido improved during the study period (2010-2020). This study emphasized that healthcare accessibility through places such as emergency hospitals and primary stroke centers was important in determining cerebral infarction mortality at the municipality level. In addition, this study identified municipalities with high mortality rates that require healthcare policy changes. The impact of socioeconomic factors on stroke is a global challenge, and improving access to healthcare may reduce disparities in outcomes.

Potential crowdedness of mechanical thrombectomy and cerebral infarction mortality in Japan: Application of inverted two-step floating catchment area method.

OBJECTIVES: This study aimed to evaluate a stroke medical delivery system based on population coverage and the potential crowdedness index (PCI) of mechanical thrombectomy and investigate the relationship between PCI and cerebral infarction mortality in Japan. MATERIALS AND METHODS: This cross-sectional study defined 662 facilities and 1605 neurointerventionalists as supply, population aged 55 years or older as demand, and set the reachable area for demand as 120 min in driving time. Multiple regression analysis adjusted for spatial autocorrelation was used to examine the relationship between PCI and cerebral infarction mortality. RESULTS: In the 2020 data, 99% of the population aged 55 years or older had access to mechanical thrombectomy (≤120 min), and the PCI ranged from 5876 to 129838, with a median of 30426. From 2020 to 2035, the PCI is estimated to increase (30426 to 32510), decreasing after 2035 (32510 to 29469). The PCI distribution exhibited geographical heterogeneity. High PCI values emerged in eastern Japan. According to regression analysis, the increase in PCI by 1% led to an increase of 0.13% in standardized mortality ratio of cerebral infarction in men. However, PCI did not significantly correlate with cerebral infarction mortality in women. CONCLUSIONS: PCI for hospitals based on supply and demand was geographically heterogeneous in Japan. Optimization of PCI contributes equalization of mechanical thrombectomy provision system and may improve cerebral infarction mortality.

In vitro drusen model - three-dimensional spheroid culture of retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids of human RPE cells constructed a well-differentiated monolayer of RPE with a Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between the RPE and Bruch's membrane with expression of many drusen-associated proteins, such as amyloid ß and complement components, the expression of which was altered by a challenge with oxidative stress. Artificial lipofuscin-loaded RPE spheroids yielded drusen more frequently. In the current study, we showed that drusen originates from the RPE. This culture system is an attractive tool for use as an in vitro drusen model, which might help elucidate the biogenesis of drusen and the pathogenesis of related diseases, such as AMD.

Serum zinc concentration as a potential predictor of presarcopenia in patients with chronic liver disease: a preliminary study.

Background: Presarcopenia is a common complication of chronic liver disease. However, the relationship between serum zinc concentration and presarcopenia in patients with chronic liver disease remains unclear. Herein, we examined whether serum zinc concentration could predict presarcopenia in patients with chronic liver disease. Methods: Between October 2015 and December 2019, 278 patients with chronic liver disease (median age, 68 years; women/men, 133/145; hepatitis B virus/hepatitis C virus/negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody, 55/124/99) who underwent abdominal computed tomography (CT) and simultaneous measurement of serum zinc concentration were included. Zinc deficiency and subclinical zinc deficiency were classified using serum zinc concentration cutoff values of <60 and <80 µg/dL [based on the Japanese Society of Clinical Nutrition (JSCN) guidelines], respectively. Additionally, presarcopenia was evaluated based on the skeletal muscle mass as per the Japan Society of Hepatology (JSH)'s sarcopenia criteria. Results: Univariate analysis revealed that the following factors were significantly associated with the presence of presarcopenia in patients with chronic liver disease: age (P<0.001), male sex (P<0.001), body mass index (BMI) (P<0.001), serum zinc concentration (P=0.005), fibrosis-4 index (P<0.001), and serum albumin concentration (P=0.03). Additionally, the median L3 skeletal muscle indices were as follows: men, non-presarcopenia group/presarcopenia group, 47.56/37.91 cm2/m2 (P<0.001); women, non-presarcopenia group/presarcopenia group, 41.64/32.88 cm2/m2 (P<0.001). Multivariate analysis using logistic regression analysis revealed that male sex [odds ratio (OR), 0.194; 95% confidence interval (CI): 0.089-0.419; P<0.001], BMI (OR, 0.666; 95% CI: 0.582-0.761; P<0.001), and serum zinc concentration <60 µg/dL (OR, 5.930; 95% CI: 1.480-23.80; P=0.01) were factors associated with presarcopenia. The OR for serum zinc concentration between 60 and 80 µg/dL was 1.910 (95% CI: 0.824-4.420; P=0.13). Conclusions: Low serum zinc levels may be an independent predictor of presarcopenia in patients with chronic liver disease.

Differences in the clinical presentation of necrotizing fasciitis depending on the causative pathogen.

Necrotizing fasciitis is a fatal, soft tissue infection of the skin that requires prompt treatment. Historically, most cases have been attributed to group A beta-hemolytic Streptococcus infection. However, in recent years, other bacteria have been identified as causing necrotizing fasciitis. In the current study, we analyzed cases of necrotizing fasciitis and examined the significant differences in symptoms caused by pathogenic bacteria. We included 79 patients (43 males and 36 females, mean age 65.4 years) diagnosed with necrotizing fasciitis who visited our hospital between April 2004 and July 2023. The patients were classified into five groups based on the identified pathogen: group A beta-hemolytic Streptococcus; group B beta-hemolytic streptococcus; group G beta-hemolytic Streptococcus; mixed infection, including anaerobic bacteria; and Staphylococcus (S) aureus. The clinical characteristics of patients, including treatment duration and laboratory values, were analyzed. Group G beta-hemolytic Streptococcus was more common in older patients (Bonferroni method, p < 0.05). Patients with S. aureus tended to be hyperglycemic (Bonferroni method, p < 0.05), had a higher rate of bacteremia (Fisher's direct probability test, p < 0.05), and had a longer treatment duration than the other examined groups (Bonferroni method, p = 0.0132). Although the five groups did not differ in the mortality rate, overall survival was shorter in the mixed infection group than in the other groups (log-rank test, p < 0.05). The legs were the most common site of infection in the non-mixed infection group; in the mixed infection group, the pubic area was identified as the most common site of infection, accompanied by a poor prognosis. Collectively, these findings suggest that necrotizing fasciitis can be characterized by pathogenic bacteria and that these characteristics may inversely predict the pathogen of origin.

Regional assessment of medical care provision system by principal component analysis.

Introduction: The Japanese government has promoted policies ensuring standardized medical care across the secondary medical care areas (SMCAs); however, these efforts have not been evaluated, making the current conditions unclear. Multidimensional indicators could identify these differences; thus, this study examined the regional characteristics of the medical care provision system for 21 SMCAs in Hokkaido, Japan, and the changes from 1998 to 2018. Materials and Methods: This study evaluated the characteristics of SMCAs by principal component analysis using multidimensional data related to the medical care provision system. Factor loadings and principal component scores were calculated, with the characteristics of each SMCA visually expressed using scatter plots. Additionally, data from 1998 to 2018 were analyzed to clarify the changes in SMCAs' characteristics. Results: The primary and secondary principal components were Medical Resources and Geographical Factors, respectively. The Medical Resources components included the number of hospitals, clinics, and doctors, and an area's population of older adults, accounting for 65.28% of the total variance. The Geographical Factors components included the number of districts without doctors and the population and a land area of these districts, accounting for 23.20% of the variance. The accumulated proportion of variance was 88.47%. From 1998 to 2018, the area with the highest increase in Medical Resources was Sapporo, with numerous initial medical resources (-9.283 to -10.919). Discussion: Principal component analysis summarized multidimensional indicators and evaluated SMCAs in this regional assessment. This study categorized SMCAs into four quadrants based on Medical Resources and Geographical Factors. Additionally, the difference in principal component scores between 1998 and 2018 emphasized the expanding gap in the medical care provision system among the 21 SMCAs.

Access to mechanical thrombectomy and ischemic stroke mortality in Japan: a spatial ecological study.

Background: Advances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions. Methods: We used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk. Results: The median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor's degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido. Conclusion: Access to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor's degrees or above are at risk of death from stroke.

Differences in spatial patterns of long-term care depending on severity in Hokkaido, Japan.

The increasing demand for long-term care (LTC) among the ageing population is a serious problem worldwide, which has greatly increased also in Japan since the introduction of the LTC insurance system there. Since there is a difference between insurers with respect to the proportion of people needing LTC, this study aimed at clarifying the spatial patterns of LTC. Insurer (n=156) LTC data for the period 2012-2019 were obtained from Ministry of Health, Labour, and Welfare and those needing LTC were classified into three classes: total, mild and severe with ageand sex-adjusted proportions needing LTC. Global and local Moran’s I statistics were calculated for each 2-year period to clarify the trends of global and local spatial clusters. From 2012 to 2019, the mean proportion of mild class cases increased (10.6% to 11.6%), whereas that of severe class cases decreased slightly (5.9% to 5.7%). The spatial pattern of the proportion of each class revealed positive spatial autocorrelation. Based on analysis by local Moran’s I, differences in spatial patterns were emphasised between the mild and severe classes. In Hokkaido, High-High clusters of mild cases were identified in the central and southern parts and severe ones in the northern and southern parts. Spatial patterns differed depending on the LTC class. Some insurers had distinctly higher or lower certification rates than those of their neighbourhoods.

ERRATUM: Differences in spatial patterns of long-term care depending on severity in Hokkaido, Japan.

Due to a mistake, the authors' affiliations were incorrectly reported in this article, published in Geospatial Health in 2022 (DOI: 10.4081/gh.2022.1077 - PMID: 35579241). The correct affiliations appear above. Geospatial Health DOI: 10.4081/gh.2022.1137.

Analysis of predictors after partial splenic embolization for thrombocytopenia with liver cirrhosis.

Blood transfusion, splenectomy, and partial splenic embolization (PSE) are generally performed for thrombocytopenia in patients with cirrhosis. Recently, thrombopoietin (TPO) agonists have become available, and investigations of patients who would benefit from them are necessary. Therefore, it is important to understand the fluctuations in cytokine levels associated with PSE. Therefore, fluctuations in platelet-associated immunoglobulin G (PAIgG), interleukin 6 (IL-6), and TPO levels with PSE were analyzed in this study. The study included 110 patients with liver cirrhosis and thrombocytopenia, with the aim of improving platelet counts. Fluctuations in PAIgG, IL-6, and TPO levels were investigated. The average splenic embolization ratio was 58.0% in patients with PSE. The platelet count rose significantly from 6.95 [5.40, 8.60] × 104/mL to 14.05 [10.43, 18.05] × 104/mL (P < .01), IL-6 rose significantly from 3.56 [2.53, 7.33] pg/mL to 18.90 [9.17, 32.95] pg/mL (P < .01), TPO rose significantly from 0.82 [0.52, 1.21] fmol/mL to 1.58 [0.97, 2.26] fmol/mL (P < .01), and PAIgG decreased significantly from 64.20 [38.33, 118.75] ng/107 cells to 37.50 [22.25, 70.00] ng/107 cells (P < .01). On multivariate analysis of factors related to the rate of platelet increase with PSE, primary biliary cholangitis (B = 0.475, P < .01), splenic embolization ratio (B = 0.75, P < .01), IL-6 change ratio (B = 0.019, P < .01), and PAIgG change ratio (B = -0.325, P < .01) were significant. When attempting to improve thrombocytopenia with PSE, adequate splenic embolization needs to be obtained together with improvements in IL-6, PAIgG, and TPO levels. With unsatisfactory improvement in thrombocytopenia, TPO agonist administration was considered.

Evaluation of and Intervention for Sarcopenia in Hepatology Departments: A Survey of Nurses in Japan.

Sarcopenia is associated with poor prognosis and decreased quality of life in patients with chronic liver disease (CLD). The present study aimed to clarify the dissemination of interventions such as evaluations, prevention efforts, and treatments for sarcopenia among patients in hepatology outpatient departments and wards in Japan, as well as examine the factors related to such dissemination. A cross-sectional study was performed involving nurses from hospitals accredited by the Japan Society of Hepatology. Participants completed a questionnaire regarding evaluations and interventions for sarcopenia in their department. Nurses from 72 outpatient departments and 162 wards provided responses to the questionnaire. Overall, 37.9% of outpatient departments and 37.6% of wards performed evaluations or interventions for sarcopenia. Outpatient departments and wards that evaluated sarcopenia or intervened held more workshops or training regarding sarcopenia than departments and wards that did not (outpatient departments: 52.0% vs. 12.2%, wards: 32.1% vs. 12.9%). Holding workshops or training regarding sarcopenia (outpatient departments; OR = 7.51, 95% confidence interval (CI): 2.12-26.6, wards; OR = 2.61, 95% CI: 1.11-6.15) was significantly associated with dissemination practices. These findings suggest that expanding knowledge of sarcopenia and developing practical skills among general nurses may aid in preventing sarcopenia among patients with CLD.

Optimal Skeletal Muscle Mass Index Cut-Off Values for Presarcopenia Evaluated by Computed Tomography against Dual-Energy X-ray Absorptiometry in Patients with Chronic Liver Disease.

Although dual-energy X-ray absorptiometry (DXA) and body impedance analysis are commonly used to measure skeletal muscle mass (SMM), a computed tomography (CT) scan is preferred in clinical practice. We aimed to propose the cut-off values of skeletal muscle mass index (SMI) calculated using CT scans, using DXA as the reference method. We retrospectively assessed 589 patients with chronic liver disease. The SMI was assessed using appendicular SMM by DXA and total muscle area at the level of the third lumbar vertebra (L3) calculated by CT. The cut-off value was determined with reference to the Asian Working Group for Sarcopenia criteria. DXA identified 251 (42.6%) patients as having presarcopenia. In men, the cut-off value of SMI for presarcopenia was determined to be 45.471 cm2/m2, with an area under the curve (AUC) of 0.863 (95% confidence interval (CI): 0.823 to 0.903), and in women, this value was determined to be 35.170 cm2/m2, with an AUC of 0.846 (95% CI: 0.800 to 0.892). Cohen's kappa coefficient was 0.575 (95% CI: 0.485-0.665) in men and 0.539 (95% CI: 0.438-0.639) in women.

Effect of levocarnitine administration in patients with chronic liver disease.

L-carnitine administration was reported to improve sarcopenia in patients with cirrhosis. However, the amount of evidence from previous studies is not sufficient. The present study aimed to clarify the effect of levocarnitine (L-carnitine) administration on body composition in patients with chronic liver disease (CLD). In the present study, 85 patients with L-carnitine administration and 87 control patients were enrolled and divided them into two groups, the L-carnitine administration group (LAG, n=44) and the without L-carnitine administration (controls, n=44) group, by using propensity score matching for age, sex, body mass index (BMI) and serum albumin. Δ skeletal muscle mass index (SMI)/year, Δ intramuscular adipose tissue content (IMAC)/year and Δ bone mineral density (BMD)/year were examined during L-carnitine administration. Each parameter was measured by computed tomography (CT) or dual-energy X-ray absorptiometry. The median age overall was 69 years (IQR, 64.0, 75.0); 36 were men and 52 were women. The median SMI was 37.4 cm2/m2 (IQR, 34.01, 44.34). The initial CT scans showed similar median values of SMI for the two groups [37.74 (34.17, 43.58) and 37.16 (33.83, 44.34), P=0.67]. However, the median ΔSMI/year for the LAG and controls were 0.95% (-3.07, 6.10) and -2.34% (-5.34, 0.53), respectively (P=0.003). The median Δ whole body BMD/year for the LAG and controls were -0.24% (-1.20, 0.91) and -1.04% (-2.16, 0.47), respectively (P=0.038). The median ΔIMAC/year and Δ lumbar spine BMD were not significantly different between the LAG and controls. L-carnitine administration may prevent the loss of skeletal muscle mass and BMD; therefore, it may be used as a new treatment option for osteoporosis and sarcopenia in patients with CLD.

Efficacy of Physical Activity in Prevention of Muscle Weakness in Patients With Chronic Liver Disease.

BACKGROUND: Sarcopenia is a prognostic factor for patients with liver cirrhosis and hepatocellular carcinoma, and it affects the onset of hepatic encephalopathy. Therefore, the prevention of sarcopenia contributes to the improvement of the prognosis of patients with chronic liver disease (CLD). We focused on changes of hand grip strength (HGS), one of the indicators of sarcopenia. However, there are little data investigating the impact of physical activity (PA) on HGS in patients with CLD. This study aimed to clarify whether PA contributes to the prevention of muscle weakness in patients with CLD. METHODS: This was a prospective observational study. We examined the effect of PA on changes in HGS from the baseline to the endpoint in each group. Metabolic equivalents-hour/week (METs-h/w) was used to evaluate PA. In total, 183 outpatients with CLD were analyzed. We divided participants into four groups (low PA in younger patients (n = 20), high PA in younger patients (n = 33), low PA in elderly patients (n = 47), and high PA in elderly patients (n = 83)). RESULTS: Fifty-eight percent of patients were men, and the median (interquartile range) age was 69.0 (63.0, 75.0) years. The most common etiology of liver disease was hepatitis C (38%). The frequency of living alone and low exercise habit was significantly high, and sarcopenia was more obvious in elderly patients with low PA than in those with high PA. Additionally, the elderly with low PA showed significantly reduced HGS compared to that of the elderly with high PA (-1.00 (-2.27, 0.55) kg vs. 0.10 (-1.40, 1.10) kg, P < 0.05). However, changes in HGS in younger patients were not significant (-0.02 (1.83, 1.47) kg vs. 0.25 (-2.45, 2.05) kg, P = 0.96). Logistic regression analyses identified PA as the independent factor for prevention of decrease in HGS (odds ratio: 1.91, 95% confidence interval: 1.00 - 3.62, P = 0.049). CONCLUSIONS: Young patients with low PA were characterized by a long sedentary time; however, there was no loss of HGS. In contrast, elderly patients with CLD and low PA had significantly reduced HGS compared to that in elderly patients with CLD and high PA.

Skeletal Muscle Index at Intensive Care Unit Admission Is a Predictor of Intensive Care Unit-Acquired Weakness in Patients With Sepsis.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) can be diagnosed using the Medical Research Council (MRC) score. However, such scoring may not be possible in ICU patients who may be sedated or delirious or have encephalopathy. Currently, a quantitative assessment of the cross-sectional area of the muscle is available to assess changes in skeletal muscle mass using computed tomography (CT) images. This assessment calculates the skeletal muscle index (SMI) (cm2/m2) by dividing the cross-sectional area (cm2) of the skeletal muscle at the level of the third lumbar vertebra by the square of the patient's height (m2) on CT. This study assessed the effectiveness of SMI, as measured by abdominal CT scans, in predicting the onset of ICU-AW in patients with sepsis admitted to the ICU. METHODS: We examined septic ICU patients admitted to the Niigata University Hospital ICU during 2012 - 2017 under mechanical ventilation. Patients were retrospectively divided into two groups by MRC score at ICU discharge: group AW comprised patients with an MRC score < 48, and group non-AW (NAW) comprised the remaining patients. Clinicopathological factors at ICU admission such as age, gender, underlying disease, body mass index, and SMI were compared between the two groups. Statistical analyses were performed using the Mann-Whitney U test, Fisher's exact test, receiver operator characteristic (ROC) analysis and multivariate analysis. RESULTS: A total of 31 septic patients were examined, and 23 patients met the criteria for ICU-AW. The prevalence of women was significantly higher in group AW (P < 0.05). All clinical factors, except for gender, were not significantly different between the two groups. SMI was significantly lower in group AW than in group NAW (P < 0.05). ROC analysis revealed that the cut-off value of SMI for predicting ICU-AW was 44.1, and the multivariate analysis revealed that only low SMI was a significant factor in predicting ICU-AW (P < 0.05). CONCLUSIONS: Our results show that SMI measurement at ICU admission is a valid predictive factor for ICU-AW progression in septic patients.

Relationship between pre-sarcopenia and quality of life in patients with chronic liver disease: a cross-sectional study.

AIM: This study aimed to clarify the relationship between pre-sarcopenia (PS) and quality of life (QOL) in patients with chronic liver disease (CLD). PATIENTS AND METHODS: This cross-sectional study evaluated 335 patients with CLD. PS was diagnosed on the basis of the assessment criteria by the Japan Society of Hepatology. QOL was evaluated using the short form-36. RESULTS: Patients' mean age was 69.52 ± 10.17 years, and 169 (50.4%) participants were men. The prevalence of PS was 53.7%. Patients were divided into the PS and non-pre-sarcopenia (NPS) groups. Patients in the PS group were older (71.84 ± 9.78 vs. 66.81 ± 9.97, P < 0.01) and mostly women (65.2 vs. 37.8%, P < 0.01) compared with those in the NPS group. QOL, physical function (38.30 ± 17.63 vs. 44.02 ± 14.76, P < 0.01), physical role functioning (RP) (40.63 ± 15.38 vs. 44.88 ± 13.89, P < 0.01), and bodily pain (BP) (48.42 ± 11.45 vs. 51.24 ± 10.19, P = 0.02) were significantly lower in the PS group than in the NPS group. Logistic regression analyses identified that the independent predictive factors for PS were female sex (odds ratio: 3.16, 95% confidence interval: 2.01-4.98; P < 0.01) and RP (odds ratio: 1.97, 95% confidence interval: 1.24-3.12; P < 0.01). CONCLUSION: QOL characteristics of PS patients with CLD were low physical function, RP, and BP in short form-36. In addition, social role functioning was low in the PS patients aged 65-74 years, whereas RP and BP were low in those aged at least 75 years. Female sex and RP were independent predictors of PS according to the multivariate analysis. Maintaining and increasing muscle mass in patients with CLD may contribute toward improving physical QOL.