Background: No consensus exists regarding which anthropometric measurements are related to bone mineral density (BMD), and this relationship may vary according to sex and age. A large Japanese cohort was analyzed to provide an understanding of the relationship between BMD and anthropometry while adjusting for known confounding factors. Methods: Our cohort included 10,827 participants who underwent multiple medical checkups including distal forearm BMD scans. Participants were stratified into four groups according to age (≥50 years or <50 years) and sex. The BMD values were adjusted for confounding factors, after which single and partial correlation analyses were performed. The prevalence of osteopenia was plotted for each weight index (weight or body mass index [BMI]) class. Results: Cross-sectional studies revealed that weight was more favorably correlated than BMI in the older group (R=0.278 and 0.212 in men and R=0.304 and 0.220 in women, respectively), whereas weight and BMI were weakly correlated in the younger age groups. The prevalence of osteopenia exhibited a negative linear relationship with weight among older women ≥50 years of age, and an accelerated increase was observed with decreasing weight in older men weighing <50 kg and younger women weighing <60 kg. When weight was replaced with BMI, the prevalence was low in most subgroups classified by weight. Conclusions Weight, rather than BMI, was the most important indicator of osteopenia but it might not be predictive of future bone loss.

Thalassemia is an inherited hemoglobin disorder characterized by hemolytic anemia. Reportedly, cardiopulmonary bypass (CPB) causes hemolysis; therefore, extreme caution is warranted during CPB. However, few studies have reported open heart surgery in patients with thalassemia. We report successful surgery for aortic stenosis and regurgitation (ASR) and an ascending aortic aneurysm (AsAA) in a patient with thalassemia. A 69-year-old woman was referred to our hospital for surgical management of ASR and AsAA. Comprehensive evaluation of microcytic anemia led to diagnosis of beta-thalassemia minor. We performed aortic valve and ascending aorta replacement; we used a biologic valve and performed open distal anastomosis under hypothermic circulatory arrest (25°) combined with retrograde cerebral perfusion. Non-pulsatile flow circulation was maintained using a centrifugal pump during CPB. The suction and ventilatory pressures were decreased, and we performed dilutional ultrafiltration. A spare artificial lung was connected to the CPB to avoid complications in the event of artificial lung blockage. We did not observe any hemolysis-induced adverse event during the clinical course, and the patient was discharged 20 days postoperatively. Careful preoperative evaluation is essential to confirm thalassemia before cardiovascular surgery to establish an optimal surgical strategy and avoid the risk of CPB-induced hemolysis in patients with the hematological disorder.

BACKGROUND/AIMS: Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. METHODS: A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3–4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. RESULTS: The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001). CONCLUSIONS: The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.
Body Mass Index ; Fibrosis* ; Humans ; Liver Cirrhosis ; Magnetic Resonance Imaging ; Methods ; Non-alcoholic Fatty Liver Disease* ; Retrospective Studies ; ROC Curve

BACKGROUND/AIMS: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. METHODS: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. RESULTS: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. CONCLUSIONS: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.
Asian Continental Ancestry Group ; Biological Markers ; Classification ; Diagnosis ; Fatty Liver* ; Fibrosis ; Genetic Variation* ; Genotype ; Humans ; Japan* ; Multivariate Analysis

BACKGROUND/AIMS: The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion therapy for hepatocellular carcinoma (HCC). METHODS: We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gelatin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. RESULTS: The mean free cisplatin concentrations were as follows. For group A, the mean was 48.58 microg/mL at 0 minute, 7.31 microg/mL at 5 minutes, 5.70 microg/mL at 10 minutes, and 7.15 microg/mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 microg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 microg/mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. CONCLUSIONS: These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver.
Carcinoma, Hepatocellular ; Cisplatin ; Drainage ; Drug Delivery Systems ; Ethiodized Oil ; Gelatin ; Hepatic Veins ; Humans ; Liver ; Pilot Projects

Studies have shown that postoperative disseminated intravascular coagulopathy (DIC) occurs in some patients with cardiac disease, acute aortic dissection, and ruptured abdominal aortic aneurysm. The specific pathophysiology of DIC in these settings are related to low cardiac function, shock, infection and sepsis as well as activation of coagulation cascade in the aneurysm sac or dissected aorta. A soluble form of recombinant human thrombomodulin (rhsTM) was approved in 2008 for the treatment of DIC. This report describes the safety and efficacy of rhsTM for the treatment of DIC in patients with cardiovascular disease operated in our department. Between October 2010 and March 2012, 35 patients with postoperative DIC were treated with rhsTM. Diagnosis of DIC was based on the diagnostic criteria for DIC of the Japanese Association for Acute Medicine (JAAM). During the first 6 months of the study period, after a diagnosis of DIC was made, the patients were treated with gabexate mesilate and antithrombin III, and if patients showed no improvement with conventional treatment, they received rhsTM for 6 days. During the last 10 months of the study period, patients received rhsTM soon after a diagnosis of DIC was made. Twenty seven patients survived for 28 days after rhsTM treatment, and the mortality rate was 22.9% (8/35). Patients who survived showed improvement in acute phase DIC scores, FDP levels, D-Dimer, fibrinogen and platelet counts during rhsTM treatment, but no improvement was observed in patients who died. No serious adverse events were found up to 28 days after the start of rhsTM administration. In conclusion, this study showed no adverse events of rhsTM, and further studies are needed to confirm that rhsTM administration is an effective therapeutic modality in the management of DIC after cardiovascular surgery.

Objective: We conducted a questionnaire survey to comprehend the situation regarding the collection, provision, and utilization of drug safety information at hospitals.  In addition, we asked pharmaceutical companies how they select medical institutions to provide drug safety information.  We also investigated the current situation of information provision to Tokyo Medial Center by pharmaceutical companies.
Method: A questionnaire was mailed to all hospitals in Japan.  The survey was conducted between January 13 and February 10, 2011.  Moreover, we asked thirteen pharmaceutical companies by telephone and e-mail about the implementation status of the provision of information and performed a survey at Tokyo Medical Center on the current situation of information provision by pharmaceutical companies regarding revisions to precaution sections in package inserts.
Results: The results of the questionnaire survey (response rate: 41.2%) showed that the major information sources for hospitals were medical representatives (77.8%), Drug Safety Update (50.3%) and direct mails (49.3%).  Furthermore, in the case of drugs prescribed exclusively for extramural dispensing, fewer hospitals responded that medical representatives of the pharmaceutical companies provided drug safety information and more hospitals responded that they did not obtain any drug safety information at all, compared with drugs listed in the hospital formularies.
Conclusion: To minimize the risks of drugs, healthcare professionals must collect a wide range of drug safety information and must utilize this information in their medical practice.  Therefore, it is important that pharmaceutical companies and regulatory authorities make an effort to provide suitable information dissemination to medical institutions.  Furthermore, medical institutions must also strengthen their systems for collecting drug safety information and providing such information to healthcare professionals.

Miriplatin is a novel lipophilic platinum complex that was developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, little prospective data are available regarding the clinical toxicity of chemotherapeutic agents used to treat HCC patients with chronic renal failure. In a phase II study, the plasma concentration of total platinum in patients who received miriplatin was very low, and no severe renal toxicity caused by miriplatin injection was reported. Here, we present three cases of HCC with stage 4 chronic renal failure who received transcatheter arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83 years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively. Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min, respectively. All cases were treated for unresectable HCC with transcatheter arterial chemotherapy with miriplatin. No serious adverse events were observed, and serum creatinine levels did not elevate, even in the patient who experienced renal failure caused by cisplatin administration. These results might suggest that transcatheter arterial chemotherapy with miriplatin can be safely used in HCC patients with chronic renal failure.
Carcinoma, Hepatocellular ; Cisplatin ; Creatinine ; Glomerular Filtration Rate ; Humans ; Kidney Failure, Chronic ; Male ; Organoplatinum Compounds ; Plasma ; Platinum ; Renal Insufficiency

A 52-year-old man suddenly felt severe back pain and numbness in the lower extremities. Enhanced CT revealed an acute Stanford type B dissection. The true lumen of the left common iliac artery was severely compressed by the thrombosed false lumen. We performed a femoro-femoral bypass and symptoms in the lower limbs disappeared. On day 4 of hospitalization, the patient suddenly presented with pain at rest and cyanosis in both lower extremities. CT revealed nearly total occlusion of the abdominal aorta due to severe compression of the false lumen. We performed emergency open graft replacement in the infrarenal aorta. Although ischemia in the lower extremities improved, the patient developed myonephropathic metabolic syndrome (MNMS) and received continuous hemodiafiltration to treat acute renal insufficiency. The patient's ankle-branchial pressure index improved and he was weaned from continuous hemodiafiltration. The patient had no paralysis and was able to walk unassisted, so he was discharged on day 34 of hospitalization. In the event of acute aortic dissection and organ ischemia, emergency open graft replacement may be required and must be performed promptly as a lifesaving measure.

A 47-year-old man underwent a double-valve replacement involving aortic valve replacement (AVR) and mitral valve replacement (MVR) and Re-Re-DVR 6 and 8 months, respectively, after an initial DVR because of suspected prosthetic valve endocarditis. Detachment of the prosthetic mitral valve occurred during the early postoperative period, for which the patient again underwent treatment 15 and 21 months after the initial surgery. The operative findings showed that the detachment was caused by a wide cleavage of the aortic-mitral continuity. There were bacteria detected on a blood culture, and his C-reactive protein (CRP) level did not reduce at any time. On the basis of these findings, we suspected nonrheumatic inflammatory disease and started steroid therapy. His CRP level became negative, and further prosthetic mitral valve detachment did not recur.