Relationship between trunk intramuscular adipose tissue content and prevalence of metabolic syndrome in middle-aged Japanese men.

OBJECTIVES: The aim of the present study was to examine the dose-response relationship between trunk tissue composition and prevalence of metabolic syndrome (MetS) in middle-aged Japanese men. METHODS: The 1026 men (between 35 and 59 y of age) who participated in the present study were divided into two groups: those with metabolic syndrome (MetS) and those without (non-MetS). Intramuscular adipose tissue (IntraMAT) content and the cross-sectional areas (CSAs) of visceral adipose tissue and skeletal muscle tissue were calculated using low-dose computed tomography images acquired at the level of the third lumbar vertebra. Height, body mass, body fat, waist circumference, the presence of MetS, and lifestyle habits were also assessed. RESULTS: IntraMAT content was significantly higher in MetS than in non-MetS men. A 10% increase in IntraMAT content correlated with the prevalence of MetS (odds ratio, 4.197; 95% confidence interval, 3.108-7.088; P < 0.001), even after adjustments for age, height, adjusted skeletal muscle CSA, sleeping time, alcohol consumption, exercise habit, and cigarette smoking. Skeletal muscle CSA did not correlate with the prevalence of MetS after adjustments for IntraMAT content and other cofactors. CONCLUSIONS: Increase in IntraMAT content, not in skeletal muscle CSA, significantly correlated with the prevalence of MetS. These results suggest that countermeasures against the accumulation of trunk IntraMAT effectively prevent MetS in middle-aged Japanese men.

Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study.

BACKGROUND: High lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese. METHODS: A genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP. RESULTS: No significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28-3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04-4.37) and 1.61 (additive, 95%CI: 1.00-2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 - 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22-0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06-2.77). CONCLUSIONS: None of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted.

Long-term survival with nivolumab followed by irinotecan after total gastrectomy in alpha-fetoprotein-producing gastric cancer: a case report and review of the literature.

BACKGROUND: Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare type of aggressive gastric cancer (GC) with a dismal prognosis. We present a patient with AFPGC who achieved long-term survival through a multidisciplinary approach. CASE PRESENTATION: A 67-year-old man with advanced GC was referred to our hospital for systemic chemotherapy. He was diagnosed with cStage IVB AFPGC. During 2nd-line treatment, we could not control bleeding from the GC itself. After complete resection, during chemotherapy, portal venous tumor thrombi (PVTTs) and liver metastases were identified. With nivolumab followed by irinotecan, the PVTTs and liver metastases disappeared. Without immunotherapy and chemotherapy for 23 months, the patient has survived for 48 months so far with no recurrence of GC. CONCLUSION: Long-term survival with AFPGC can be accomplished by using several different approaches, such as surgery, immunotherapy, and chemotherapy.

Computer-aided diagnosis of early-stage colorectal cancer using nonmagnified endoscopic white-light images (with videos).

BACKGROUND AND AIMS: Differentiation of colorectal cancers (CRCs) with deep submucosal invasion (T1b) from CRCs with superficial invasion (T1a) or no invasion (Tis) is not straightforward. This study aimed to develop a computer-aided diagnosis (CADx) system to establish the diagnosis of early-stage cancers using nonmagnified endoscopic white-light images alone. METHODS: From 5108 images, 1513 lesions (Tis, 1074; T1a, 145; T1b, 294) were collected from 1470 patients at 10 academic hospitals and assigned to training and testing datasets (3:1). The ResNet-50 network was used as the backbone to extract features from images. Oversampling and focal loss were used to compensate class imbalance of the invasive stage. Diagnostic performance was assessed using the testing dataset including 403 CRCs with 1392 images. Two experts and 2 trainees read the identical testing dataset. RESULTS: At a 90% cutoff for the per-lesion score, CADx showed the highest specificity of 94.4% (95% confidence interval [CI], 91.3-96.6), with 59.8% (95% CI, 48.3-70.4) sensitivity and 87.3% (95% CI, 83.7-90.4) accuracy. The area under the characteristic curve was 85.1% (95% CI, 79.9-90.4) for CADx, 88.2% (95% CI, 83.7-92.8) for expert 1, 85.9% (95% CI, 80.9-90.9) for expert 2, 77.0% (95% CI, 71.5-82.4) for trainee 1 (vs CADx; P = .0076), and 66.2% (95% CI, 60.6-71.9) for trainee 2 (P < .0001). The function was also confirmed on 9 short videos. CONCLUSIONS: A CADx system developed with endoscopic white-light images showed excellent per-lesion specificity and accuracy for T1b lesion diagnosis, equivalent to experts and superior to trainees. (Clinical trial registration number: UMIN000037053.).

Skeletal muscle and abdominal circumference explain intramuscular fat, independent of exercise frequency, in middle-aged Japanese men.

The purpose of this study was to examine how intramuscular adipose tissue (IntraMAT) can be characterized using physical and functional characteristics, muscle size, and/or adipose tissue in four different exercise frequency groups of middle-aged Japanese men. One thousand twenty-eight middle-aged men (age, 47.5 ± 8.1 years; height, 170.5 ± 5.8 cm; body mass, 67.0 ± 9.3 kg; body mass index, 21.9 ± 5.3 kg/m2) were allocated to four groups on the basis of their weekly exercise frequency: Group 1, no exercise, n = 334; Group 2, once a week, n = 271; Group 3, a few days a week, n = 269; and Group 4, every day, n = 154. Their body composition, blood pressure, and handgrip strength were assessed. A single-slice computerized tomography image at the level of the umbilicus was acquired and the CSAs of IntraMAT, muscle tissue, and subcutaneous and visceral adipose tissues (SCAT and VAT) were calculated. The %IntraMAT significantly correlated with physical characteristics, such as age, BMI, abdominal circumference, and muscle tissue CSA. Stepwise multiple regression analysis was performed, with the %IntraMAT as the dependent variable. Muscle tissue CSA and abdominal circumference were the common independent variables across groups to explain the variability of the %IntraMAT. It was also extracted %body fat and age for Group 2, age, handgrip strength, and BMI for Group 3, and smoking category for Group 4. These results suggested that muscle tissue size and abdominal circumference would be the strong predictors to explain %IntraMAT of the trunk muscle across four groups, and that age, %body fat, BMI, and SCAT, handgrip strength and smoking category were also good predictors for each group with different exercise frequency in middle-aged Japanese men.

Relationship between Seasonal Changes in Food Intake and Energy Metabolism, Physical Activity, and Body Composition in Young Japanese Women.

We investigated seasonal changes in food intake, energy metabolism, and physical activity (PA) and explored their associations with body composition. In total, 28 women aged 20−23 years in the Kansai area of Japan participated in this year-long study spanning the winter, spring, and summer seasons. A dietary investigation was performed using the weight recording method, and the amount of histidine in the diet, which may be related to the regulation of energy intake, was calculated. Resting metabolic rate (RMR), body composition, and PA were measured using indirect calorimetry, bioelectrical impedance analysis, and uniaxial accelerometry, respectively. The results showed that energy intake was highest in winter, decreased significantly with increasing temperature, and decreased by 25% in summer. As the intake of histidine in the diet did not increase in summer, it did not seem to be involved in the suppression of energy intake. RMR was highest in winter and decreased significantly in summer by 20%. The amount of PA was low in winter, increased significantly in the spring, and decreased again in summer. Body weight increased in winter, with an accumulation of fat in the trunk and arms, and decreased in summer, with a reduction in the amount of fat. Greater energy intake and less PA in winter induced an increment in body weight despite the increase in RMR. There were no significant changes in lean body mass between the seasons; however, the muscle weight of the lower limbs increased significantly in spring and in summer compared with that in winter (p < 0.001). Thus, seasonal changes in food intake, energy metabolism, and PA occur, with resultant changes in the body composition under comfortable air-conditioned environments.

Contribution of skeletal muscle and serum lipids to muscle contraction induced by neuromuscular electrical stimulation in older individuals.

Intramyocellular lipids (IMCL) stored in droplets in muscle cells and free fatty acids (FFA) from fat cells in the blood are the main substrates of adenosine triphosphate during continuous muscle contractions of relatively lower intensity. Although it is known that the lipid oxidative capacity decreases with aging, the effect of IMCL and FFA on muscle contraction in older individuals remains unclear. The purpose of this study was to investigate the contribution of skeletal muscle lipids and blood lipids as energy sources for muscle contraction in older individuals. Eighteen older individuals (mean age: 70.4 ± 3.5 years) underwent muscle contraction intervention induced by intermittent neuromuscular electrical stimulation (NMES) to the vastus lateralis for 30 min. Fasting blood samples were obtained and proton magnetic resonance spectroscopy (1 H-MRS) was performed before and after NMES, and the parameters (including IMCL and extramyocellular lipid [EMCL]) from 1 H-MRS, along with FFA and adiponectin levels, were analyzed using the blood samples of all participants. Levels of IMCL and EMCL did not change (p > 0.05); however, FFA and adiponectin levels decreased from 1.1 ± 0.5 mEq/L to 0.8 ± 0.2 mEq/L and 12.0 ± 5.3 µg/ml to 11.4 ± 5.0 µg/ml, after NMES (p < 0.05), respectively. These findings indicate that serum lipids, but not skeletal muscle lipids, are the energy substrate utilized during involuntary muscle contraction in older individuals.

Risk of Delayed Bleeding after Cold Snare Polypectomy in Patients with Antithrombotic Therapy.

BACKGROUND: Cold snare polypectomy is being increasingly adopted; however, there are few reports of cold snare polypectomy regarding antithrombotic therapy. AIMS: This study aimed to investigate the real-world safety of cold snare polypectomy during antithrombotic therapy. METHODS: We collected data from consecutive patients undergoing cold snare polypectomy in a single hospital between 2013 and 2017. Indications for cold snare polypectomy were any ≤ 10 mm polyp. The primary outcome was delayed bleeding. We compared rates of delayed bleeding between patients with and without antithrombotic therapy and analyzed risk factors for delayed bleeding using binary logistic regression model with firth procedure. RESULTS: In 2152 patients (mean age 67.6 years; male 1411), 4433 colorectal polyps (mean diameter 5.0 mm) underwent cold snare polypectomy. Clipping during the procedure was performed for 5.8%. Delayed bleeding occurred in 0.51% (11/2152) of patients and 0.25% (11/4433) of polyps, but no major delayed bleeding occurred. A total of 244 (11%) patients received antithrombotic therapy. Patients on antithrombotic therapy were older (p < 0.001), more likely male (p < 0.001) and had cold snare polypectomy in the proximal colon (p = 0.011). The rate of delayed bleeding was higher in patients on antithrombotic therapy (1.64% vs. non-antithrombotic therapy 0.37%, p = 0.009). Larger polyp size (> 5 mm), use of clips, and antithrombotic therapy were significant risk factors for delayed bleeding. There was no clear association between specific antithrombotic agents and delayed bleeding. CONCLUSIONS: Delayed bleeding after cold snare polypectomy was rare even in patients with antithrombotic therapy, and no major delayed bleeding occurred.

Effect of a 1-year intervention comprising brief counselling sessions and low-dose physical activity recommendations in Japanese adults, and retention of the effect at 2 years: a randomized trial.

BACKGROUND: In an effort to increase people's adherence to active lifestyles, contemporary physical activity (PA) guidelines now include low-dose PA. METHODS: PA was evaluated in 583 participants of the Nutritional and Physical Activity Intervention Study (NEXIS) cohort (30-65 years old); 349 inactive participants (MVPA, 2.7 ± 1.0 MET-h/day) were randomly assigned to the intervention or control groups, and 235 active participants participated in follow-up visits. The intervention aimed to increase MVPA and comprised five brief counseling sessions over 1 year. The 1-year target for the participant was increasing their step-count to 10,000 steps/d or +3000 steps/d, relative to the baseline score. The counseling sessions were designed to stimulate progressive changes in physical behaviors by recommendations promoting small and/or light-intensity bouts of PA. PA was measured at baseline, the end of the intervention, and 1 year after the intervention ended. Additionally, several nutrition, health, and fitness parameters were measured. RESULTS: Participants in the intervention group significantly increased their step-count from 8415 ± 1924 at baseline to 9493 ± 2575 at the end of the 1-year period. During the same period, MVPA significantly increased by 0.9 MET-h. The daily time spent in ≥ 3, ≥ 4 and ≥ 5 MET activities increased by 11, 6, and 3 min, respectively. This increase in PA remained observable 1 year after intervention concluded. The active group maintained higher physical activity levels throughout the two years. The intervention group showed smaller energy intakes at the end of the 2-year period. Significant correlations were noted between the 1-year change in MVPA and the change in resting heart rate (r = - 0.22), and between the 2-year change in MVPA and the change in waist circumference (r = - 0.08) and peak oxygen consumption capacity (r = 0.23) in the intervention group only. CONCLUSIONS: A prolonged and progressive PA intervention promoting small bouts of light-to-moderate PA may be used in healthy, not-optimally-active people to increase PA beyond the strict period of the intervention. Further studies are necessary to understand whether low-dose PA messages can be effective in initiating a progressive increase toward larger amounts of PA. TRIAL REGISTRATION: Clinical Trials.gov, NCT00926744, retrospectively registered.

Survey of chemotherapy-induced nausea and vomiting in patients with urothelial carcinoma.

Chemotherapy-induced nausea and vomiting (CINV) can cause anorexia, weight loss and deterioration of patient quality of life. It is one of the most unpleasant adverse effects of chemotherapy treatment regimens. For the optimal treatment of gastrointestinal symptoms during urothelial carcinoma chemotherapy, the present study investigated the association between gastrointestinal symptoms and therapeutic effects of gemcitabine plus platinum [cisplatin (GC) or carboplatin (GCa)] therapies. The incidence and frequency of nausea/vomiting with GC split therapy (gemcitabine, 1,000 mg/m2 on days 1 and 8; split-dose cisplatin, 35 mg/m2 on days 1 and 8; 21-day schedule) and GCa therapy [gemcitabine, 750-1,000 mg/m2 on days 1, 8 and 15; carboplatin, area under the blood concentration-time curve=5 mg min/ml (Calvert formula) on day 2; 28-day schedule] were lower compared with those of GC therapy (gemcitabine, 1,000 mg/m2 on days 1, 8 and 15; single-dose cisplatin 70 mg/m2 on day 2; 28-day schedule). However, no differences in therapeutic outcomes were observed among therapies. GCa therapy, regardless of renal function, and GC split therapy demonstrated significant increases compared with GC therapy in alleviating gastrointestinal symptoms associated with cancer chemotherapy in patients with urothelial carcinoma. Overall, these results suggested that split-dose cisplatin administration or the use of carboplatin instead of cisplatin may be useful in patients who experience CINV without compromising treatment effectiveness.

Comparison of metabolic risk factors, physical performances, and prevalence of low back pain among categories determined by visceral adipose tissue and trunk skeletal muscle mass in middle-aged men.

The present study compared metabolic risk factors, physical performances, and musculoskeletal impairment among categories determined by visceral adipose tissue (VAT) and trunk skeletal muscle (SM) mass in middle-aged Japanese men. In total, 1026 healthy Japanese males aged between 35 and 59 years were categorized into 4 groups according to the amount of VAT and SM in the trunk measured using low-dose computed tomography (LowVAT-HighSM, LowVAT-LowSM, HighVAT-HighSM, and HighVAT-LowSM). Height, body mass waist circumference, body fat, intramuscular adipose tissue (IntraMAT), subcutaneous adipose tissue, biochemical blood profiles (triglycerides, high-density lipoprotein cholesterol, fasting blood glucose, aspartate transaminase, alanine transaminase and γ-glutamyl trans peptidase), physical performances (trunk flexibility, the chair-stand test, two-step length and hand-grip strength), the prevalence of low back pain, and lifestyle habits for exercise, alcohol intake and smoking, were compared among the groups. The results showed that LowVAT-HighSM had significantly superior biochemical blood profiles and physical performances to the other groups. HighVAT-LowSM had significantly higher %IntraMAT and the prevalence of low back pain. The two-step length, which is an index of walking ability, significantly differed according to the four subject categories. These results indicate that metabolic risk factors, physical performances, and prevalence of low back pain in middle-aged Japanese men may differ among four categories determined by VAT and trunk SM.

Comparison of 18F-FDG PET/CT and 67Ga-SPECT for the diagnosis of fever of unknown origin: a multicenter prospective study in Japan.

OBJECTIVE: The aim of this multicenter prospective study was to compare the sensitivity of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of 67Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO). METHODS: The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by 67Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and 67Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and 67Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient's attending physician. The clinical impacts (four grades) of FDG-PET/CT and 67Ga-SPECT on the final diagnosis were evaluated. RESULTS: A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study's analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1-58.2%) was significantly higher than that for 67Ga-SPECT (25%, 95% CI 15.5-37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for 67Ga-SPECT (57%, P < 0.001). CONCLUSIONS: FDG-PET/CT showed a superior sensitivity to 67Ga-SPECT for the identification of the site of greatest importance for the final diagnosis of the cause of FUO.

Importance of Paravascular Vitreal Adhesions for Development of Myopic Macular Retinoschisis Detected by Ultra-Widefield OCT.

PURPOSE: To examine most postequatorial retina in eyes with myopic macular retinoschisis (MRS) by ultra-widefield (UWF) OCT and to determine whether paravascular vitreal adhesions play a role in the development of MRS. DESIGN: Retrospective single-center observational case series. PARTICIPANTS: One hundred fifty highly myopic participants who were older than 50 years with and without an MRS were studied. High myopia was defined as an eye with an axial length of more than 26.5 mm. METHODS: All participants underwent UWF OCT imaging with a scan width of 23 mm and a depth of 5 mm using a prototype swept-source OCT device. The vitreoretinal adhesions to the foveal retina and retinal vessels and paravascular abnormalities, including paravascular retinal cysts, paravascular retinoschisis, and paravascular lamellar holes, were analyzed in the UWF OCT images. The findings in eyes with an MRS were compared with those in eyes without an MRS. MAIN OUTCOME MEASURES: The relationships between MRS and vitreal adhesions to the retinal vessels or to the fovea were determined. RESULTS: An MRS was found in 49 of the 150 eyes (33%). Vitreal adhesions to the retinal vessels were found more frequently in eyes with an MRS than in eyes without an MRS (63% vs. 44%; P = 0.04). In contrast, the number of eyes with adhesions to the fovea in eyes with an MRS was not significantly different from that in eyes without an MRS (57% vs. 59%). Paravascular lesions, for example, retinal cysts, retinoschisis, and lamellar holes, were more common in eyes with an MRS than in eyes without an MRS (71% vs. 36%, 61% vs. 17 %, and 20% vs. 8% [P < 0.001, P < 0.001, and P = 0.03], respectively). Multivariate analysis showed that the presence of paravascular vitreal adhesions was a significant predictor for MRS development (odds ratio, 2.56; P = 0.02). CONCLUSIONS: Paravascular vitreal adhesions may be related to the development of the different types of paravascular lesions including retinal cysts and retinoschisis, and play a more important role in the development of an MRS than vitreal adhesions to the fovea.

Validation of the NSABP/NRG Oncology 8-Gene Trastuzumab-benefit Signature in Alliance/NCCTG N9831.

Our objective was to validate the NSABP 8-gene trastuzumab-benefit signature, developed and initially validated in NRG Oncology/NSABP B-31 in Alliance/NCCTG N9831. The B-31 and N9831 trials demonstrated the benefit of adding trastuzumab to chemotherapy in the adjuvant setting for HER2+ breast cancer patients. NSABP investigators utilized gene expression profiles of N9831 patients (N = 892) to blindly assign patients to large-, moderate-, or no-trastuzumab benefit groups and then NCCTG investigators assessed the degree of trastuzumab benefit using Cox models adjusted for age, nodes, estrogen receptor/progesterone receptor status, tumor size, and grade. Hazard ratios and 2-sided P values for recurrence-free survival of the predicted large- (n = 387), moderate- (n = 401), and no-benefit (n = 104) groups, based on the 8-gene signature were 0.47 (95% CI = 0.31 to 0.73, P < .001), 0.60 (95% CI = 0.39 to 0.92, P = .02), and 1.54 (95% CI = 0.59 to 4.02, P = .38), respectively (P interaction  = .02), providing validation of the 8-gene signature in an independent study.

False-Positive Elevation of CK-MB Levels with Chest Pain in Lung Adenocarcinoma.

The creatinine kinase (CK)-MB assay can be used for the early diagnosis of acute coronary syndrome. We describe the case of an 82-year-old male with lung adenocarcinoma who presented with chest pain. While laboratory findings showed elevated CK-MB levels, there was no cardiac injury. A chest computed tomography scan revealed pleural carcinomatosis. Later, electrophoretic analysis of CK showed a normal CK-MB range but increased CK-BB levels and the presence of macro CK type 2. We determined that the patient's chest pain originated from the visceral pleural invasion of lung cancer. Because of the methods used to measure the CK-MB isozyme, the CK-MB level appeared elevated.

Attempt of Bayesian Estimation from Left-censored Data Using the Markov Chain Monte Carlo Method: Exploring Cr(VI) Concentrations in Mineral Water Products.

Hexavalent chromium (Cr(VI)) is toxic, carcinogenic, and mutagenic substances. Oral exposure to Cr(VI) is thought to be primarily from drinking water. However, under the certain reporting limit (~0.1 µg/L), percentage of Cr(VI) concentration in mineral water products under the reporting limit were estimated higher than 50%. Data whose values are below certain limits and thus cannot be accurately determined are known as left-censored. The high censored percentage leads to estimation of Cr(VI) exposure uncertain. It is well known that conventional substitution method often used in food analytical science cause severe bias. To estimate appropriate summary statistics on Cr(VI) concentration in mineral water products, parameter estimation using the Markov chain Monte Carlo (MCMC) method under assumption of a lognormal distribution was performed. Stan, a probabilistic programming language, was used for MCMC. We evaluated the accuracy, coverage probability, and reliability of estimates with MCMC by comparison with other estimation methods (discard nondetects, substituting half of reporting limit, Kaplan-Meier, regression on order statistics, and maximum likelihood estimation) using 1000 randomly generated data subsets (n = 150) with the obtained parameters. The evaluation shows that MCMC is the best estimation method in this context with greater accuracy, coverage probability, and reliability over a censored percentage of 10-90%. The mean concentration, which was estimated with MCMC, was 0.289×10-3 mg/L and this value was sufficiently lower than the regulated value of 0.05 mg/L stipulated by the Food Sanitation Act.

Successful Desensitization with Crizotinib after Crizotinib-induced Liver Injury in ROS1-rearranged Lung Adenocarcinoma.

Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes. We report a patient with ROS1-rearranged lung adenocarcinoma who developed a crizotinib-induced mixed/cholestatic type of liver injury. The patient discontinued crizotinib after 34 days due to liver toxicity. Twenty-four days later, when transaminases and C reactive protein (CRP) were normalized, crizotinib was resumed using an oral desensitization method. The patient was successfully treated for manageable recurrence of liver injury and has been able to continue the treatment.

Pilot prescription survey of antineoplastic agents: real-world data from veterinary teaching hospitals in Japan.

The collection of real clinical records from veterinary practices and analysis of these records helps to establish evidence-based veterinary medicine and further improves animal health and welfare. Prior to the collection of nationwide clinical records, we downloaded the data from the digital accounting systems of two veterinary teaching hospitals in Japan, and the prescriptions of antineoplastic agents were surveyed for a 5-year period from 2009 to 2013. The ratio of the number of patients prescribed antineoplastic agents to the total number of prescriptions was <5% at both hospitals, and >80% of those patients were dogs. The overall number of prescriptions included more oral rather than injectable formations, whereas among antineoplastic agents, injectable formulations were prescribed more frequently at both hospitals. The most frequently prescribed agents were almost identical at both hospitals: platinum compounds, such as carboplatin and cisplatin (CDDP), vincristine and doxorubicin. The most frequently prescribed product combined with CDDP was doxorubicin at Hospital A. Antiemetic agents combined with CDDP included dexamethasone, ondansetron and metoclopramide, but these antiemetic agents were combined fewer than 10 times among 197 CDDP prescriptions. The prescription history, including the number of prescriptions, dosing intervals and combined medications, was provided by the survey. Although the present database consisted of data from two hospitals, our results indicate that a broad analysis can be conducted using integrated data from multiple hospitals and practices for further cohort studies.

Greater analgesic effect with intermittent compared with continuous mode of lumbar plexus block for total hip arthroplasty: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Lumbar plexus block (LPB) is an effective perioperative analgesic therapy for patients undergoing total hip arthroplasty (THA). However, the analgesic efficacy of intermittent administration compared with continuous infusion of LPB in patients remains unclear. METHODS: Forty adult patients who underwent THA were randomly divided into two groups: continuous infusion group (6 mL/hour continuous infusion of levobupivacaine [0.125%] in LPB, n=20) and intermittent infusion group (12 mL of levobupivacaine [0.125%] bolus delivered every 2 hours in LPB, n=20). The primary outcome was the cumulative fentanyl consumption administered for rescue analgesia during the first 48 hours after surgery. Secondary outcomes were the number of demands for rescue analgesia and successfully delivered rescue analgesia; extent of sensory blockade (cold tests); and pain score on the visual analog scale (VAS) at rest and during mobilization during the first 48 hours after surgery. RESULTS: Both the cumulative fentanyl consumption administered for rescue analgesia (mean [SD]: 81.5 [58.5] µg vs 438 [101.2] µg among the intermittent infusion and the continuous infusion groups, respectively) and the number of demanded and delivered fentanyl boluses for rescue analgesia were lower in intermittent infusion group than in continuous infusion (p<0.001 for both). The extent of sensory blockade remained constant in intermittent infusion group, but gradually narrowed in continuous infusion. VAS was lower in intermittent infusion group than in continuous infusion, except at 1 and 12 hours postoperatively (p<0.05). CONCLUSIONS: Greater analgesic effect was achieved using the intermittent mode than the continuous mode of LPB administration.

Post-Marketing Surveillance of Silodosin in Patients with Benign Prostatic Hyperplasia and Poor Response to Existing Alpha-1 Blockers: The SPLASH Study.

OBJECTIVES: Our objective was to investigate the effectiveness and safety of silodosin in patients with benign prostatic hyperplasia (BPH) who switched to silodosin from another α1 blocker because of inadequate response. METHODS: This was a prospective observational study conducted at 715 medical facilities in Japan in patients with BPH who received an α1 blocker other than silodosin for at least 3 months but had experienced unsatisfactory treatment outcomes. Patients completed questionnaires, including the International Prostate Symptom Score (IPSS), quality of life (QOL) score and Overactive Bladder Symptom Score (OABSS) at baseline (time of switching) and after 3 months of treatment with silodosin. RESULTS: Overall, 3355 patients were assessed for safety and 3144 patients for effectiveness. Mean ± standard deviation age was 73.1 ± 8.2 years, and most patients had been receiving tamsulosin (53.6%) or naftopidil (45.5%) before silodosin. Silodosin was well tolerated, with an overall incidence of adverse drug reactions of 8.1% and no unexpected safety signals. Significant improvements were observed after switching to silodosin in all effectiveness outcome measures, including total IPSS, all IPSS subscale scores, QOL score, total OABSS, all OABSS subscale scores and residual urine volume. Significant improvements in total IPSS were seen in patients who had been receiving tamsulosin or naftopidil before switching and in almost all other patient subgroups, with the exception of patients with mild symptoms (total IPSS ≤ 7) at baseline. CONCLUSIONS: This post-marketing analysis indicates that switching to silodosin from tamsulosin or naftopidil significantly improved symptoms associated with BPH, and silodosin was well tolerated in Japanese patients.