Risk factors for fracture by same-level falls among workers across sectors: a cross-sectional study of national open database of the occupational injuries in Japan.

OBJECTIVES: The hospitalisation rate for work-related injuries among older workers is double that of younger workers; however, the risk factors for same-level fall fractures sustained during industrial accidents remain unclear. This study aimed to estimate the influence of worker age, time of day and weather conditions on the risk of same-level fall fractures in all industrial sectors in Japan. STUDY DESIGN: This was a cross-sectional study. METHODS: This study used the population-based national open database of worker death and injury reports in Japan. In total, 34,580 reports of occupational same-level falls between 2012 and 2016 were used in this study. Multiple logistic regression analysis was performed. RESULTS: In primary industries, workers aged ≥55 years had a 1.684 times greater risk of fracture (95% confidence interval [CI]: 1.167-2.430) compared with workers aged ≤54 years. In tertiary industries, relative to the odds ratio (OR) of injuries recorded at 0:00-2:59 a.m., the ORs recorded at 6:00-8:59 p.m., 6:00-8:59 a.m., 9:00-11:59 p.m. and 0:00-2:59 p.m. were 1.516 (95% CI: 1.202, 1.912), 1.502 (95% CI: 1.203-1.876), 1.348 (95% CI: 1.043-1.741) and 1.295 (95% CI: 1.039-1.614), respectively. The risk of fracture increased with a 1-day increase in the number of snowfall days were per month in secondary (OR = 1.056, 95% CI: 1.011-1.103) and tertiary (OR = 1.034, 95% CI: 1.009-1.061) industries. The risk of fracture decreased with every 1-degree increase in the lowest temperature in primary (OR = 0.967, 95% CI: 0.935-0.999) and tertiary (OR = 0.993, 95% CI: 0.988-0.999) industries. CONCLUSIONS: With the increasing number of older workers and changing environmental conditions, the risk of falls in the tertiary sector industries is increasing, particularly just before and just after shift change hours. These risks may be associated with environmental obstacles during work migration. It is also important to consider the weather-associated risks of fracture.

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy.

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire. Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet's content and quality, respondents' satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale. Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet. Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

A validation study of combined resection and ablation therapy for multiple hepatocellular carcinoma.

AIM: To validate the utility of hepatic resection combined with complementary radiofrequency ablation (RFA) compared with resection alone for patients with multiple hepatocellular carcinoma (HCC), and to compare these results with those of a previous report. MATERIALS AND METHODS: A total of 78 HCC patients with multiple (≤5) tumours who were initially treated with hepatic resection only (Resection group) or with combined hepatic resection and RFA (Combination group) were included. Overall and disease-free survival were analysed. RESULTS: There were 21 women and 57 men with a median age of 72.5 (64.3-76.8) years. Fifty-three patients were treated with resection alone and 25 received combination therapy. The 3-, 5-, and 7-year cumulative overall survival rates were 81.2%, 68.2%, and 57.1%, respectively, in the Resection group, and 81.3%, 59.6%, and 42.4%%, respectively, in the Combination group (hazard ratio [HR], 1.462; 95% confidence interval [CI], 0.682-3.136; p=0.329). The 1-, 3-, and 5-year cumulative disease-free survival rates were 61.4%, 45.7%, and 39.8%, respectively, in the Resection group, and 53.1%, 18.6%, and 0%, respectively, in the Combination group (HR, 2.080; 95% CI, 1.157-3.737; p=0.014). The overall survival rate was not significantly different between the Resection and Combination groups in patients within the up-to-seven HCC criteria (n=56; HR, 2.101; 95% CI, 0.805-5.486; p=0.130) or those beyond these criteria (n=22; HR, 0.804; 95% CI, 0.197-3.286; p=0.761). CONCLUSIONS: The combination of hepatic resection and RFA therapy may be an effective strategy for HCC patients with multiple tumours.

Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib.

BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.

The natural course of the paravertebral muscles after the onset of osteoporotic vertebral fracture.

This study revealed the change in the paravertebral muscles in patients with osteoporotic vertebral fracture. Increased pain is likely to be the driver for reduced activity, reduced activities of daily living, and consequent increase in fat infiltration of the paravertebral muscles, assumed to be secondary to reduced activity level or, conversely, partial immobilization. INTRODUCTION: To reveal the time courses and impact of the paravertebral muscles (PVMs) on the healing process of osteoporotic vertebral fractures and risk factors for PVM decrease. METHODS: Consecutive patients with symptomatic osteoporotic vertebral fractures were enrolled in 11 hospitals. At enrollment and 3- and 6-month follow-up, PVMs, including the multifidus and erector spinae, were examined using magnetic resonance imaging (MRI). The PVM cross-sectional area (CSA) and fat signal fraction (FSF) were measured at L3. Low back pain (LBP), activities of daily living (ADLs), and risk factors for PVM decrease at the 6-month follow-up were investigated. PVM decrease was defined as > 1 standard deviation decrease of the CSA or > 1 standard deviation increase of the FSF. RESULTS: Among 153 patients who completed the 6-month follow-up, 117 (92 women, 79%) had MRI of L3 at enrollment and 3- and 6-month follow-up (mean age at enrollment, 78.5 years). The CSA did not change 6 months from onset (p for trend = 0.634), whereas the FSF significantly increased (p for trend = 0.033). PVM decrease was observed in 30 patients (26%). LBP was more severe, and delayed union was more frequent in patients with PVM decrease (p = 0.021 mixed-effect model and p = 0.029 chi-square test, respectively). The risk factors for PVM decrease were ADL decline at the 3-month follow-up (adjusted odds ratio = 5.35, p = 0.026). CONCLUSION: PVM decrease was significantly related to LBP and delayed union after osteoporotic vertebral fracture onset. ADL decline at the 3-month follow-up was a risk factor for PVM decrease. Therefore, restoring ADLs within 3 months after onset is important.

Viral eradication reduces both liver stiffness and steatosis in patients with chronic hepatitis C virus infection who received direct-acting anti-viral therapy.

BACKGROUND: Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS: A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS: Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. CONCLUSION: Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).

Differences in background characteristics of patients with chronic hepatitis C who achieved sustained virologic response with interferon-free versus interferon-based therapy and the risk of developing hepatocellular carcinoma after eradication of hepatitis C virus in Japan.

We compared the background characteristics of patients with chronic hepatitis C who achieved eradication of hepatitis C virus (HCV), that is sustained virologic response (SVR), with interferon (IFN)-based versus IFN-free antiviral therapy in Japan. In addition, we used a previously reported risk assessment model to compare the incidence of hepatocellular carcinoma (HCC) after SVR by treatment type. Pretreatment characteristics of 1533 patients who achieved SVR with IFN-based therapy and 1086 patients with IFN-free therapy from five institutions across Japan were compared. The risk of HCC after SVR was assessed based on pretreatment characteristics, and the incidence of HCC after SVR was estimated in both groups. Age and serum alpha-fetoprotein levels were higher, platelet count was lower, and liver fibrosis was more advanced in patients who achieved SVR with IFN-free therapy compared with IFN-based therapy. The incidence of HCC after SVR in the IFN-free group was estimated to be more than twofold higher than in the IFN-based therapy group (7.29% vs. 3.09%, and 6.23% vs. 3.01% when excluding patients who have underwent curative treatment for HCC). There are large differences in pretreatment characteristics between patients who achieved SVR with IFN-based and IFN-free therapies in Japan, which are associated with differential risk of HCC after SVR. These differences can influence the incidence of HCC after SVR and should be taken into consideration when comparing IFN-based and IFN-free therapies in terms of hepatocarcinogenesis suppression with HCV eradication.

Core I97L mutation in conjunction with P79Q is associated with persistent low HBV DNA and HBs antigen clearance in patients with chronic hepatitis B.

OBJECTIVES: When considering treatment for chronic hepatitis B (CHB), it is important to discriminate between patients with persistent low HBV DNA and patients with active hepatitis, who may proceed to cirrhosis. In this study, we sought to identify mutations in patients expected to have persistent low HBV DNA and ultimately exhibit clearance of hepatitis B surface antigen (HBsAg). METHODS: Serum samples were obtained from 33 CHB genotype C patients, divided based on HBV DNA and alanine aminotransferase (ALT) levels following observation for >2 years: Group A (n=10), transient HBV DNA ≥5.0 log copies/mL and ALT ≥120 IU/L; Group B (n=11), persistent HBV DNA <5.0 and ALT <60; and Group C (n=12), persistent HBV DNA <4.0 and ALT <30. Full-length HBV sequences were compared among groups. Subsequently, 82 patients with CHB were evaluated for the I97L mutation and the additional mutation P79Q. We compared cumulative incidences of persistent low HBV DNA and HBsAg clearance in patients with or without I97L and P79Q by the Kaplan-Meier method. RESULTS: Incidence of Core mutation I97L differed significantly among groups: A, 30% (3/10); B, 36.4% (4/11); C, 83.3% (10/12) (p = 0.021). Cumulative incidences of persistent low HBV DNA and HBsAg clearance were significantly higher in patients with I97L than in those with wild-type I97 (p = 0.003 and p = 0.016, respectively), and even higher in those with P79Q. CONCLUSIONS: In patients with CHB, measurement of I97L and additional mutation P79Q would be useful for predicting persistent low HBV DNA, normal ALT, and HBsAg clearance.

Time course of osteoporotic vertebral fractures by magnetic resonance imaging using a simple classification: a multicenter prospective cohort study.

This study revealed the time course of osteoporotic vertebral fracture by magnetic resonance imaging using a simple classification. Signal changes were associated with the compression degree and mobility of the fractured vertebral body. This classification showed sufficient reliability in categorizing magnetic resonance imaging findings of osteoporotic vertebral fractures. INTRODUCTION: Magnetic resonance imaging (MRI) is useful in diagnosing osteoporotic vertebral fractures (OVFs). This study investigated the time course of OVFs by MRI using a simple classification. METHODS: This multicenter cohort study was performed from 2012 to 2015. Consecutive patients with ≤2-week-old OVFs were enrolled in 11 institutions. MRI was performed at enrollment and at 1-, 3-, 6-, and 12-month follow-up. Signal changes on T1-weighted imaging (T1WI), T2WI, and short τ inversion recovery (STIR) were classified according to signal intensity. Height and angular motion of vertebral bodies were also measured. RESULTS: The 6-month follow-up was completed by 153 patients. At enrollment, fractured vertebrae signal changes were 43 % diffuse and 57 % confined low on T1WI; on T2WI, 56, 24, and 5 % were confined low, high, and diffuse low, respectively; on STIR, 100 % were high. On T1WI, diffuse low remained most common (90 % at 1 month and 60 % at 3 months) until 6 and 12 months, when most were confined low (54 and 52 %, respectively). On T2WI, confined low remained most common (decreasing to 41 % at 12 months). On STIR, high signal change was shown in 98, 87, and 64 % at 3, 6, and 12 months, respectively. At 3, 6, and 12 months, diffuse low signal change was associated with significantly lower vertebral height, and high signal change was associated with significantly greater angular motion. CONCLUSIONS: MRI signal changes were associated with the compression degree and angular motion of fractured vertebrae. This classification showed sufficient reliability in categorizing MRI findings of OVFs.

Predicting delayed union in osteoporotic vertebral fractures with consecutive magnetic resonance imaging in the acute phase: a multicenter cohort study.

This study demonstrated the predictive values of radiological findings for delayed union after osteoporotic vertebral fractures (OVFs). High-signal changes on T2WI were useful findings. INTRODUCTION: The purpose of the present study is to determine predictive radiological findings for delayed union by magnetic resonance imaging (MRI) and plain X-rays at two time points in the acute phase of OVFs. METHODS: This multicenter cohort study was performed from 2012 to 2015. A total of 218 consecutive patients with OVFs ≤2 weeks old were enrolled. MRIs and plain X-rays were performed at the time of enrollment and at 1- and 6-month follow-ups. Signal changes on T1-weighted imaging (T1WI) were classified as diffuse low-, confined low-, or no-signal change; those on T2WI were classified as high (similar to the intensity of cerebrospinal fluid), confined low-, diffuse low-, or no-signal change. The angular motion of the fractured vertebral body was measured with X-rays. RESULTS: A total of 153 patients completed the 6-month follow-up. A high-signal change on T2WI was most useful in predicting delayed union. Sensitivity, specificity, and positive predictive values were 53.3, 87.8, and 51.6 % at enrollment and 65.5, 84.8, and 51.4 % at the 1-month follow-up, respectively. The positive predictive value increased to 62.5 % with observation of high- or diffuse low-signal changes at both enrollment and the 1-month follow-up. The cutoff value of vertebral motion was 5 degrees. Sensitivity and specificity at enrollment were 52.4 and 74.1 %, respectively. CONCLUSIONS: This study demonstrated the radiological factors predicting delayed union after an OVF. T2 high-signal changes showed the strongest association with delayed union. Consecutive MRIs were particularly useful as a differential tool to predict delayed union following OVFs.

High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references.

Statistical imputation of classical human leukocyte antigen (HLA) alleles is becoming an indispensable tool for fine-mappings of disease association signals from case-control genome-wide association studies. However, most currently available HLA imputation tools are based on European reference populations and are not suitable for direct application to non-European populations. Among the HLA imputation tools, The HIBAG R package is a flexible HLA imputation tool that is equipped with a wide range of population-based classifiers; moreover, HIBAG R enables individual researchers to build custom classifiers. Here, two data sets, each comprising data from healthy Japanese individuals of difference sample sizes, were used to build custom classifiers. HLA imputation accuracy in five HLA classes (HLA-A, HLA-B, HLA-DRB1, HLA-DQB1 and HLA-DPB1) increased from the 82.5-98.8% obtained with the original HIBAG references to 95.2-99.5% with our custom classifiers. A call threshold (CT) of 0.4 is recommended for our Japanese classifiers; in contrast, HIBAG references recommend a CT of 0.5. Finally, our classifiers could be used to identify the risk haplotypes for Japanese narcolepsy with cataplexy, HLA-DRB1*15:01 and HLA-DQB1*06:02, with 100% and 99.7% accuracy, respectively; therefore, these classifiers can be used to supplement the current lack of HLA genotyping data in widely available genome-wide association study data sets.

Utility of the FIB-4 Index for hepatocarcinogenesis in hepatitis C virus carriers with normal alanine aminotransferase levels.

The FIB-4 index is a simple formula using age, aspartate aminotransferase, alanine aminotransferase (ALT) and platelet count to evaluate liver fibrosis. We investigated the ability of the FIB-4 index for hepatocarcinogenesis in hepatitis C virus (HCV) carriers with normal ALT levels. A total of 516 patients with ALT levels persistently at or below 40 IU/L during an observation period of over 3 years were included. Factors associated with the development of HCC were determined. Hepatocellular carcinoma (HCC) developed in 60 of 516 patients (11.6%). The incidence rate of HCC at 5 and 10 years was 2.6% and 17.6%, respectively. When patients were categorized according to the FIB-4 index as ≤ 2.0 (n = 226), >2.0 and ≤ 4.0 (n = 169), and > 4.0 (n = 121), the cumulative incidence of HCC at 5 years was 0.5%, 1.3% and 8.0%, respectively, and 2.8%, 25.6% and 37.1% at 10 years, respectively. Patients with FIB-4 index >4.0 were at the highest risk (P < 0.001). Factors that were significantly associated with HCC in the multivariate analysis were FIB-4 index >2.0 (hazard ratio (HR), 7.690), FIB-4 index >4.0 (HR, 8.991), α-fetoprotein (AFP) >5 ng/mL (HR, 2.742), AFP >10 ng/mL (HR, 4.915) and total bilirubin >1.2 mg/dL (HR, 2.142). A scoring system for hepatocarcinogenesis that combines the FIB-4 index and AFP predicted patient outcomes with excellent discriminative ability. The FIB-4 index is strongly associated with the risk of HCC in HCV carriers with normal ALT levels.

Direct evidence for three-dimensional off-axis trapping with single Laguerre-Gaussian beam.

Optical tweezers are often applied to control the dynamics of objects by scanning light. However, there is a limitation that objects fail to track the scan when the drag exceeds the trapping force. In contrast, Laguerre-Gaussian (LG) beams can directly control the torque on objects and provide a typical model for nonequilibrium systems such as Brownian motion under external fields. Although stable "mid-water" trapping is essential for removing extrinsic hydrodynamic effects in such studies, three-dimensional trapping by LG beams has not yet been clearly established. Here we report the three-dimensional off-axis trapping of dielectric spheres using high-quality LG beams generated by a special holographic method. The trapping position was estimated as ~ half the wavelength behind the beam waist. These results establish the scientific groundwork of LG trapping and the technical basis of calibrating optical torque to provide powerful tools for studying energy-conversion mechanisms and the nonequilibrium nature of biological molecules under torque.

Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.

BACKGROUND: The Japanese 'BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients. METHODS: In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance. RESULTS: The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival. CONCLUSIONS: The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts.

Changes in hepatitis C virus genotype distribution in Japan.

Genotypes are associated with the natural course of hepatitis C virus (HCV) infection and response to antiviral therapy for HCV. HCV genotype 1b has been the dominant genotype in Japan, where the prevention of HCV transmission through blood transfusion or nosocomial infection has been established since 1990. The distribution of HCV genotype was investigated based on patient's birth year in 5515 HCV-infected Japanese individuals at three institutions from different areas of Japan. At all three institutions, the proportion of HCV genotype 1b decreased and was <50% in individuals born after 1970. By contrast, the percentage of HCV genotype 2b increased in subsequent birth cohorts after 1920-1929. Significant changes in HCV genotype distribution were observed across Japan regardless of area.

Targeted destruction of fungal structures of Erysiphe trifoliorum on flat leaf surfaces of Marchantia polymorpha.

In this study, we observed the germination behaviour of airborne conidia from powdery mildews that settle on thalloid surfaces. We inoculated thalli (flat, sheet-like leaf tissues) and gemmae (small, flat, sheet-like leaf tissues that propagate asexually via bud-like structures) of the common liverwort (Marchantia polymorpha) with conidia from tomato powdery mildew (Oidium neolycopersici; KTP-02) and red clover powdery mildew (Erysiphe trifoliorum; KRCP-4N) and examined their germination and subsequent appressorium formation under a high-fidelity digital microscope. Conidial bodies and germ tubes of the inoculated KRCP-4N conidia were destroyed on both the thalli and gemmae. The destruction of these fungal structures was observed only for KRCP-4N conidia inoculated onto M. polymorpha on both leaf surfaces. No differences in destruction of the KRCP-4N fungal structures between thalli and gemmae were observed. At 4 h post-inoculation, destruction of the germ tube tip was observed when it reached the gemmae leaf surface. At 6 h post-inoculation, the conidial bodies and germ tubes were destroyed. In contrast, KTP-02 conidia were not destroyed and formed normal, well-lobed appressoria on the surface of M. polymorpha gemmae.

Gauze packing as damage control for uncontrollable haemorrhage in severe thoracic trauma.

INTRODUCTION: The usefulness of thoracic damage control (DC) for trauma requiring a thoracotomy is not established. The aim of this study was to clarify the usefulness of thoracic packing as DC surgery. METHODS: This was a retrospective case series study of 12 patients with thoracic trauma suffering uncontrollable intrathoracic haemorrhage and shock who underwent intrathoracic packing. Our thoracic DC technique consisted of ligation and packing over the bleeding point or filling gauze in the bleeding spaces as well as packing for the thoracotomy wound. The success rates of intrathoracic haemostasis, changes in the circulation and the volume of discharge from the thoracic tubes were evaluated. RESULTS: Packing was undertaken for the thoracic wall in five patients, for the lung in four patients, for the vertebrae in two patients and for the descending thoracic aorta in one patient. Haemostasis was achieved successfully in seven cases. Of these, the volume of discharge from the thoracic tube exceeded 400 ml/hr within three hours after packing in three patients, decreased to less than 200 ml/hr within seven hours in six patients and decreased to 100ml/hr within eight hours in six patients. Systolic pressure could be maintained over 70 mmHg by seven hours after packing. CONCLUSIONS: Intrathoracic packing is useful for some patients, particularly in the space around the vertebrae, at the lung apex, and between the diaphragm and the thoracic wall. After packing, it is advisable to wait for three hours to see whether vital signs can be maintained and then to wait further to see if the discharge from the thoracic tube decreases to less than 200 ml/hr within five hours.