Kumamoto University Hospital

The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas.

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).

OBJECTIVE: Our purpose was to evaluate the relationships between the ratio of maximum relative cerebral blood volume (rCBV) (rCBV ratio = rCBV[tumor]/rCBV[contralateral white matter]) and histologic and angiographic vascularities of gliomas using the gradient-echo echoplanar MR imaging technique. We also evaluated the usefulness of rCBV maps for grading gliomas. SUBJECTS AND METHODS: We examined 30 patients with histologically verified gliomas. Gliomas were classified as glioblastoma, anaplastic glioma with enhancement, anaplastic glioma without enhancement, and low-grade glioma. The maximum rCBV ratio of each glioma was compared with both histologic and angiographic vascularities, and the relationship between the maximum rCBV ratios and each type of glioma was established. RESULTS: The maximum rCBV ratios of the gliomas significantly correlated with both histologic and angiographic vascularities (p < .001). Mean values and SDs of maximum rCBV ratios of each type of tumor were 7.32+/-4.39 for glioblastomas, 5.84+/-1.82 for anaplastic gliomas with enhancement, 1.53+/-0.75 for anaplastic gliomas without enhancement, and 1.26+/-0.55 for low-grade gliomas. The maximum rCBV ratios of the glioblastomas were significantly higher than those of the anaplastic gliomas without enhancement (p = .002) and the low-grade gliomas (p < .001). The maximum rCBV ratios of the anaplastic gliomas with enhancement were higher than those of the anaplastic gliomas without enhancement and the low-grade gliomas, but the differences were not statistically significant (p = .08 and p = .03, respectively). CONCLUSION: The results of perfusion-sensitive MR imaging with gradient-echo echoplanar technique correlated with both histologic and angiographic vascularities.

This report was written by the Japanese Society of Dysphagia Rehabilitation, the Japanese Association of Rehabilitation Nutrition, the Japanese Association on Sarcopenia and Frailty, and the Society of Swallowing and Dysphagia of Japan to consolidate the currently available evidence on the topics of sarcopenia and dysphagia. Histologically, the swallowing muscles are of different embryological origin from somatic muscles, and receive constant input stimulation from the respiratory center. Although the swallowing muscles are striated, their characteristics are different from those of skeletal muscles. The swallowing muscles are inevitably affected by malnutrition and disuse; accumulating evidence is available regarding the influence of malnutrition on the swallowing muscles. Sarcopenic dysphagia is defined as dysphagia caused by sarcopenia of the whole body and swallowing-related muscles. When sarcopenia does not exist in the entire body, the term "sarcopenic dysphagia" should not be used. Additionally, sarcopenia due to neuromuscular diseases should be excluded; however, aging and secondary sarcopenia after inactivity, malnutrition and disease (wasting disorder and cachexia) are included in sarcopenic dysphagia. The treatment of dysphagia due to sarcopenia requires both dysphagia rehabilitation, such as resistance training of the swallowing muscles and nutritional intervention. However, the fundamental issue of how dysphagia caused by sarcopenia of the swallowing muscles should be diagnosed remains unresolved. Furthermore, whether dysphagia can be caused by primary sarcopenia should be clarified. Additionally, more discussion is required on issues such as the relationship between dysphagia and secondary sarcopenia, as well as the diagnostic criteria and means for diagnosing dysphagia caused by sarcopenia. Geriatr Gerontol Int 2019; 19: 91-97.

We describe the results of conservative treatment for complete midsubstance tears of the anterior cruciate ligament (ACL) in 18 skeletally immature patients, followed for a minimum of 36 months. Six patients had an ACL reconstruction during the follow-up period and were assessed immediately before their operation. The average time from initial injury to evaluation was 51 months. All patients had symptoms when reviewed. The modified Lysholm knee score showed one excellent result, one good, eight fair, and eight poor with a mean score of 64.3. Only one patient had returned to her preinjury level of athletics. Secondary meniscal tears were confirmed in six patients, and three more had the clinical signs of a tear at follow-up. Radiological evidence of degenerative changes was found in 11 of the 18 patients. We conclude that the results of non-operative treatment for ACL injuries in this age group are poor and not acceptable.

The current guideline represents the 6th edition of the 'Japanese Clinical Practice Guideline for Diabetes' which has been revised every three years since its first appearance in 2004 to promote evidence-based, rational, efficient and consistent clinical practice in diabetes. Of note, dramatic progress has been made in recent years in diabetes research and clinical practice, which includes approval of antidiabetic agents with novel mechanisms of action along with publication of clinical trial results with these drugs, and novel diagnostic and therapeutic devices, such as continuous glucose monitoring (CGM) and sensor augmented pumps (SAP). Again, results from large-scale clinical trials in Japan, such as J-DOIT 1 to 3 and JDCP studies, have recently been reported. Further, in the last three years, new guidelines for lipid and blood pressure control have been released in a timely fashion from the Japan Atherosclerosis Society and the Japanese Society of Hypertension. Therefore, the current guideline has been compiled to include not only relevant advances in clinical practice but novel findings and new lines of evidence that have been made available to date. While the current guideline has been organized along similar lines to those of the preceding 2016 edition and using the same clinical questions (CQs) and questions (Qs) format, each CQ or Q has been closely reviewed for revision and further CQs or Qs have been added as appropriate to further promote the use of the guidelines in clinical practice. Readers are therefore referred to the 'Methods of developing the "Japanese Clinical Practice Guideline for Diabetes 2019"' for a detailed account of the guideline development processes involved to make effective use of the current guideline. It is hoped that the guideline will prove a helpful guide to evidence-based medicine (EBM) in clinical settings thereby contributing not only to prolongation of healthy lifespan but to improved quality of life in patients with diabetes. The guideline consists of general questions (cited as Qs) and clinical questions (cited as CQs) followed by explanations. Statements of recommendation were developed solely for CQs. Clinical guideline committee (CGC) members conducted systematic review (SR) of evidence from several resources to develop a statement of recommendation for CQs and presented a strength of recommendation rated as a grade. SR support team helped CGC members to make literature retrieval and confirm an evidence level for articles that they obtained. A brief criterion of the literature retrieval process was shown in this guideline. We referred to all the important articles necessary for the judgement of a statement and its strength of recommendation for CQs. Abstract tables were constructed solely for the articles necessary to recommend a statement for CQs. They contained relevant articles with PICO (Populations, Interventions, Comparators, Outcomes of interest), study design, and evidence level as defined in Table 1. The quality of evidence was also summarized based on 5 items for meta-analysis or systematic review, and 3 items for randomized controlled trial as shown in Table 1. The grade of recommendation was determined by each CGC member with consideration given to certainty of overall evidence, balance of benefits and harms, patient preferences/values, and costs (Table 2). Grades A and B stand for strong and weak recommendations, respectively. The CGC members reviewed and discussed all CQ guidelines. Votes were taken for each recommendation statement. A 75% agreement among eligible CGC members was required to approve each recommendation and its strength. Satisfies all of the following 5 items: Satisfies all of the following 3 items: I. Type 1 (Characterized by pancreatic β-cell destruction usually leading to absolute insulin deficiency) III. Diabetes due to some other specific mechanism or disease Individuals who have met the above criteria 1–3 are to be diagnosed with acute-onset (autoimmune) type 1 diabetes. Those who have met the above criteria 1, 2, and 4 are to be diagnosed with acute-onset type 1 diabetes. Those who have met the above criteria 1 and 2 but not 3 and 4 are to be re-evaluated after an interval with the diagnosis put on hold. Those who have met the criteria for fulminant type 1 diabetes are to be diagnosed as such. Some may lead to the onset of ketosis or ketoacidosis within about 1–2 weeks. The onset of fulminant type 1 diabetes may be associated with pregnancy. Exocrine pancreatic enzymes, e.g., amylase, lipase, and esterase 1, are shown to be elevated in 98% of affected individuals. Upper airway and gastrointestinal symptoms are noted in 70% of affected individuals. Fulminant type 1 diabetes is shown to be linked to HLA DRB1*04:05–DQB1*04:01. [Q2-3] How is the glycemic goal to be set for each individual patient? (Figure 5) Glucose levels in affected individuals are to be controlled as close to normal as possible. Achieving and maintaining favorable glycemic control early after initiation of treatment is likely to lead to favorable long-term outcomes in these individuals1. [Q2-4] How is the onset of chronic diabetic complications prevented or their progression delayed? Diabetes management is aimed not merely at glycemic control1 but also at ensuring continued smoking cessation and control of blood pressure and lipid levels, thereby preventing chronic diabetic complications or delaying their progression2-5. [CQ3-2] Is MNT education by registered dieticians effective? MNT education by registered dieticians is effective10, 11 (grade A: 95% agreement). As per the statement on target body weight vs total energy intake, for each patient, his/her target body weight and total energy intake is to be individually determined. Again, all values given below are primarily intended as suggested targets only and therefore need to be modified, as required, during patient consultation, in consideration of each patient's current body weight, glycemic control and other parameters. There is also a need for accumulating evidence for body weight and total energy intake determination. For elderly patients, the coefficient could be made larger than that associated with their actual level of physical activity to prevent them from developing frailty. Conversely, for obese patients in a weight loss program, the coefficient could be made lower than that associated with their actual level of physical activity. In either case, individuals whose actual body weight widely differs from their target body weight, the coefficient could be flexibly determined with consideration given to the levels of physical activity and corresponding energy coefficients to given above. Given that insulin is shown to have a wide-ranging action affecting not only glucose metabolism but lipid and protein metabolism, all of which are closely linked, energy-producing nutrients as components of MNT must be assessed for their balance and validity against each patient's disease condition, as well as associated risks including hyperglycemia. Furthermore, consideration is to be given not only to the safety of the dietary components but to Japanese cuisine culture and patient preferences, to ensure long-term implementation of MNT. However, there is no evidence available to support the effectiveness of any particular dietary nutrient ratios that contribute to long-term management of diabetes. To ensure long-term implementation of MNT in patients with diabetes, priority is to be given to honoring their eating habits and preferences thus allowing them to enjoy their meals as far as they do not defeat the purpose of MNT medically, while at the same time giving consideration to any potential risks associated with their individual diet regimens. Advantage: This Scr-based formula offers convenience by allowing renal function to be estimated with a blood test alone. With this formula, eGFR is likely to fall ± 30% of measured GFR (mGFR) in 75% of patients. Disadvantage: Adjusted for average body surface area (BSA) (1.73 m2), the formula is likely to be associated with a greater estimation error in patients of large and small build. The formula is also associated with overestimated values in patients with low muscle mass. Advantage: Secreted from all nucleated cells, cysteine C is thought less likely to be influenced by muscle mass or dietary content. Disadvantage: Adjusted for average BSA (1.73 m2), the formula is also likely to be associated with a greater estimation error in patients of large and small build. Subjective symptoms of diabetic polyneuropathy are characterized as: Findings of interest (diabetic neuropathy is to be confirmed if one of the following two has been met, despite failure to meet the criteria described above) [Q15-3] What is the office blood pressure threshold for initiating antihypertensive therapy in patients with diabetes? (Table 7, Figure 6) [CQ15-4] Is controlling office blood pressure to <130/80 mmHg effective in preventing the onset of complications in patients with diabetes and hypertension? (Figure 7) GDM is diagnosed if one or more of the following criteria have been met in a 75 g OGTT: ① Fasting blood glucose value ≥92 mg/dL ② 1-h post-OGTT glucose value ≥180 mg/dL ③ 2-h post-OGTT glucose value ≥153 mg/dL Overt diabetes in pregnancy is diagnosed if ① or ② below has been met: ① Fasting blood glucose value ≥126 mg/dL ② HbA1c ≥6.5% ① Diabetes mellitus diagnosed before pregnancy ② Pregnancy associated with unequivocal evidence of diabetic retinopathy <5.3 mmol/L*4 (<95 mg/dL) 1-h PPG <140 mg/dL Or 2-h PPG <120 mg/dL 1-h PPG <140 mg/dL Or 2-h PPG <120 mg/dL 1-h PPG <7.8 mmol/L (<140 mg/dL) Or 2-h PPG <6.4 mmol/L (115 mg/dL) [I-CQ-1] Is there any relationship between aging and impaired glucose tolerance? [I-CQ-2] What are the characteristics of diabetes in the elderly? [I-CQ-3] What are the complications associated with diabetes in the elderly? [II-CQ-1] Are the diagnostic criteria employed for diabetes in the elderly similar to those used for diabetes in adults? [II-CQ-2] Are elderly patients with diabetes susceptible to postprandial hyperglycemia? [II-CQ-3] Are elderly patients with diabetes susceptible to hyperosmolar hyperglycemic state (HHS)? [II-CQ-4] How is hypoglycemia characterized in elderly patients with diabetes? [II-CQ-5] Are elderly patients with diabetes associated with drug-related adverse events? [II-CQ-6] Is diabetes in the elderly associated with an increased incidence of atherosclerotic disease? [II-CQ-7] Is the risk of mortality increased in elderly patients with diabetes compared to that in those without? [II-CQ-8] Are elderly patients with diabetes likely to be associated with cognitive impairment or dementia? [II-CQ-9] What psychological states need to be watched for in elderly patients with diabetes? [II-CQ-10] Are elderly patients with diabetes associated with impairment of physical function? [III-CQ-1] What do elderly patients with diabetes need to be assessed for? [III-CQ-2] Why do elderly patients with diabetes need to be assessed for cognitive function? [III-CQ-3] How are elderly patients with diabetes screened for cognitive impairment? [III-CQ-4] How are elderly patients with diabetes assessed for physical function? [IV-CQ-1] What complications should elderly patients with diabetes be assessed for? [IV-CQ-2] Should elderly patients with diabetes be referred to an ophthalmologist for assessment of diabetic retinopathy? [IV-CQ-3] Should elderly patients with diabetes be assessed regularly for urinary albumin/protein values and estimated glomerular filtration rates (eGFR)? [IV-CQ-4] How are elderly patients with diabetes assessed for diabetic neuropathy and cared for? [IV-CQ-5] What infections are elderly patients with diabetes susceptible to? Summary [IV-CQ-6] Are these infections amenable to prevention with pneumococcal and influenza vaccines? [V-CQ-1] Is diabetes or hyperglycemia a likely risk factor for cognitive impairment or onset of dementia in the elderly? [V-CQ-2] Is severe hypoglycemia a likely risk factor for cognitive impairment or onset of dementia in the elderly? [V-CQ-3] Is tight glycemic control effective in reducing cognitive impairment or dementia in elderly patients with diabetes? [VI-CQ-1] Is hyperglycemia a likely risk factor for decreased ADL, sarcopenia, and falls/fractures in elderly patients with diabetes? [VI-CQ-2] Is low HbA1c or hypoglycemia a likely risk factor for falls/fractures or frailty in elderly patients with diabetes? [VI-CQ-3] Is glycemic control effective in maintaining ADL in elderly patients with diabetes? [VI-CQ-4] Is diabetes or hypoglycemia a likely risk factor for depression (depression or depressive tendency) in the elderly? [VII-CQ-1] Is glycemic control effective in inhibiting the onset or progression of complications in elderly patients with diabetes? [VII-CQ-2] Is glycemic control effective in preventing infections in elderly patients with diabetes? [VII-CQ-3] Is there any relationship between HbA1c values and the onset of macroangiopathy or mortality? [VII-CQ-4] Should tight glycemic control be implemented in elderly patients with diabetes? [VII-CQ-5] What are the considerations to be kept in mind in determining the glycemic control goal for elderly patients with diabetes? [VIII-CQ-1] Is MNT as effective for elderly patients with diabetes as for non-elderly patients? [VIII-CQ-2] What are the considerations to be kept in mind in determining adequate energy intake at initiation of therapy for elderly patients with diabetes? * While the term 'ideal body weight' was used in this section of the Japanese version of the current Guidelines in reference to the Clinical Practice Guidelines for the Management of Diabetes in the Elderly 2017, the term 'target body weight' is used, instead of 'ideal body weight', to ensure consistency with that used in the Chapter 3 on Medical nutrition therapy (MNT) of the current English-language version. [VIII-CQ-3] What are the considerations to be kept in mind in determining adequate carbohydrate, protein and lipid intakes for elderly patients with diabetes? [VIII-CQ-4] Is dietary sodium (salt) restriction effective for elderly patients? [VIII-CQ-5] Is there any relationship between vitamin/fatty acid intake and cognitive impairment in elderly patients with diabetes? [VIII-CQ-6] Is there any dietary pattern recommended for elderly patients with diabetes? [VIII-CQ-7] Is there any relationship between inadequate vitamin D/calcium intake and bone mineral density (BMD)? [VIII-CQ-8] How are elderly patients with diabetes assessed for undernutrition? [IX-CQ-1] Is physical activity/exercise effective in improving glycemic control, cognitive function, ADL, depression and QOL in elderly patients with diabetes? [X-CQ-1] What are the precautions to be kept in mind when implementing glucose-lowering therapy in elderly patients with diabetes? [X-CQ-2] Is the use of sulfonylureas (SUs) likely to cause hypoglycemia in elderly patients with diabetes? [X-CQ-3] Does metformin reduce cardiovascular death in elderly patients with diabetes? [X-CQ-4] Is metformin a risk factor for lactic acidosis in elderly patients with diabetes? [X-CQ-5] What are the precautions to be kept in mind when using oral hypoglycemic agents other than SUs or metformin, as well as GLP-1 receptor agonists, in elderly patients with diabetes? [X-CQ-6] Is multi-drug combination therapy a risk factor for hypoglycemia or falls in elderly patients with diabetes? [XI-CQ-1] What are the precautions to be kept in mind when implementing insulin therapy in elderly patients with diabetes? [XII-CQ-1] Are hypoglycemic symptoms in elderly patients with diabetes similar to those in younger adults? [XII-CQ-2] What are the risk factors for hypoglycemia in elderly patients with diabetes? [XII-CQ-3] What are the precautions against diabetes sick days characterized by the onset of fever, diarrhea, vomiting and decreased appetite? [XIII-CQ-1] Is antihypertensive management effective in reducing the onset or progression of diabetic microangiopathy and macroangiopathy in elderly patients with diabetes? [XIII-CQ-2] Is antidyslipidemic management effective in reducing the onset or progression of macroangiopathy in elderly patients with diabetes? [XIV-CQ-1] Is diabetes in elderly patients a likely risk factor for nursing home institutionalization? [XIV-CQ-2] What are the characteristics of institutionalized elderly patients with diabetes? [XV-CQ-1] What are the precautions to be kept in mind in providing terminal care for elderly patients with diabetes? [Q21-1] How are patients assessed to determine their risk of type 2 diabetes? Various risk factors have been identified for type 2 diabetes, and a risk model (risk scores) is currently being developed for type 2 diabetes in Japanese1-3. Eiichi Araki received honoraria from AstraZeneca, Daiichi Sankyo, Kowa, Mitsubishi Tanabe Pharma, MSD, Novo Nordisk, Ono Pharmaceutical and Sanofi, also received subsidies or donations from Astellas Pharma, Bayer Yakuhin, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk, Pfizer Japan, Sanofi, Sumitomo Dainippon Pharma, Taisho Pharmaceutical and Takeda Pharmaceutical, and belongs to endowed departments by MSD, Ono Pharmaceutical and Terumo. Mitsuhiko Noda received subsidies or donations from Astellas Pharma, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly Japan, Mitsubishi Tanabe Pharma, MSD, Novo Nordisk Pharma, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Takeda Pharmaceutical and Teijin Pharma. Hiroshi Noto received honoraria from Eli Lilly Japan and MSD. Haruhiko Osawa received research funding from Daiichi Sankyo, Ono Pharmaceutical, Sysmex, Taisho Toyama Pharmaceutical and Takeda Pharmaceutical. Yukio Tanizawa received honoraria from Astellas Pharma, MSD, Novo Nordisk Pharma, Ono Pharmaceutical and Takeda Pharmaceutical, also received research funding from Seastar, also received subsidies or donations from Astellas Pharma, Daiichi Sankyo, Eli Lilly Japan, Kyowa Kirin, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Sanofi, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. Kazuyuki Tobe received honoraria from Novo Nordisk Pharma, Kowa Pharmaceutical and Astellas Pharma, also received research funding from The Uehara Memorial Foundation and The Naito Foundation, also received subsidies or donations from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Daiichi Sankyo, MSD, Asahi Kasei Pharma, Teijin Pharma, Boehringer Ingelheim, Ono Pharmaceutical, Novo Nordisk Pharma, Eli Lilly Japan, Fuji Chemical Industries and Arkray. Narihito Yoshioka received honoraria from Novo Nordisk Pharma and Takeda Pharmaceutical. Atsushi Goto, Tatsuya Kondo, Hideki Origasa, Akihiko Taguchi have nothing to declare. The Japan Diabetes Society: Organizational Conflict of Interest Co-sponsored seminar: Abbott Diagnostics Medical, Abbott Japan, Abbott Vascular Japan, Aegerion Pharmaceuticals, Ajinomoto, AR Brown, Arkray, Arkray Global Business, Asahi Kasei Pharma, ASKA Pharmaceutical, Astellas Pharma, AstraZeneca, Bayer Yakuhin, Cosmic Corporation, Covidien Japan, Daiichi Sankyo, Eiken Chemical, Eizai, Eli Lilly Japan, Fujifilm Pharma, Fujifilm Toyama Chemical, Fukuda Colin, Fukuda Denshi, Gilead Sciences, Hakubaku, Healthy Network, Hitachi Chemical Diagnostics Systems, Horiba, InBody Japan, Johnson & Johnson, Kaken Pharmaceutical, Kissei Pharmaceutical, Kotobuki Pharmaceutical, Kowa, Kracie Pharmaceutical, Kyowa Kirin, LifeScan Japan, LSI Medience, Medtronic Japan, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Mylan EPD, Nikkiso, Nippon Becton Dickinson, Nippon Boehringer Ingelheim, Nipro, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Rizap Group, Roche DC Japan, Sanofi, Santen Pharmaceutical, Sanwa Kagaku Kenkyusho, SRL, Sumitomo Dainippon Pharma, Taisho Pharma, Taisho Pharmaceutical, Takeda Pharmaceutical, Terumo, Unex, Welby. Supporting member: Abbott Japan, Arkray Global Business, Astellas Pharma, AstraZeneca, Bunkodo, Chugai Pharmaceutical, Daiichi Sankyo, EA Pharma, Eizai, Eli Lilly Japan, H + B Life Science, Horiba, Japan Tobacco, Johnson & Johnson, Kaken Pharmaceutical, Kissei Pharmaceutical, Kowa, Kyowa Kirin, LifeScan Japan, Medtronic Japan, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Nipro, Novo Nordisk Pharma, Ono Pharmaceutical, PHC, Roche DC Japan, Sanofi, Sanwa Kagaku Kenkyusho, Sekisui Medical, Shionogi, SRL, Sumitomo Dainippon Pharma, Sysmex, Taisho Pharma, Taisho Pharmaceutical, Takeda Pharmaceutical, Terumo, Tosoh. Research grant: Abbott Japan, Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Sanofi, Takeda Pharmaceutical. Award system: Eli Lilly Japan, Novo Nordisk Pharma, Sanofi. Funding statement: The society received no specific funding for this work. The article does not contain any studies with human or animal subjects performed by any of the authors. In recent years, clear evidence has emerged from multiple meta-analyses of the available data including those from the Japanese population to demonstrate the between diabetes and In the Diabetes and the Society released their on the relationship between diabetes and from the Japan Diabetes Society and the Japanese a the first in which its for and as well as for the general The its of the on Diabetes and in To a of studies have the between diabetes and diabetes the type 2 is to be associated with an increased risk of and as well as a risk of mechanisms of in diabetes include insulin and associated hyperglycemia and chronic However, diabetes is a risk factor for to be the between glucose-lowering agents and the risk to be is thought to be that priority be given to the benefits of favorable glycemic control with these with due given to the contained in their The of the on Diabetes and this and the of glycemic control on the risk of in patients with that there is no evidence at to the between glycemic control and risk in patients with diabetes. It is that patients with and diabetes are associated with and long-term life than patients with It is also shown that diabetic patients with are less likely to therapy than patients with with and with pancreatic and diabetes whose HbA1c is or have a lower than those whose HbA1c is less than strength is determined by bone mineral density and bone The is determined by the of bone mineral in bone and the is determined by factors including bone and in bone strength is associated with an increased risk of bone The risk of developing is increased by about to in patients with type 1 patients are characterized by decreased bone mineral but the risk of bone is It is that bone quality as well as decreased bone mineral density for decreased bone strength. The of bone quality is more in patients with type 2 diabetes than those with type 1 diabetes. The risk of developing is shown to be increased to to in those with type 2 they have greater bone mineral density than those with type 1 A meta-analysis of randomized controlled trials patients with type 2 diabetes and those not e.g., that the risk of is increased to among those The risk is shown to be increased to among but not no has been about the risk of associated with the use of GLP-1 receptor agonists, metformin, or A of data from no in or with the use of between patients with type 2 diabetes and is and and for of all performed in Japan and the of the from the and performed in Japan as of the of a of with the and rates of and respectively. is a of that from a the of a is performed on patients with diabetes shown to have severe hypoglycemia despite diabetes may not its to insulin therapy for of is to reduce the of hypoglycemia and glucose values by glycemic from were conducted to a total of patients with the between 2004 and in As in studies, HbA1c was and severe hypoglycemia among those with While the need for multiple and of long-term were among the with the of which consists of with or an receptor followed by therapy with a and an or an was to lead to the from insulin therapy in all patients with type 1 diabetes from each In Japan, from was as a of care B in patients with severe hypoglycemic a similar to that of of and is currently being implemented as to the on of and the Japan Diabetes 1 was conducted to the effectiveness of in individuals at risk of diabetes in preventing diabetes. Of the in the individuals those with impaired glucose years were identified and to the and the of the study followed all subjects for years on average by of and and no in incidence of diabetes between the and but a lower incidence among those per than among those such 3 or per in the when at each study The Diabetes 2 was an study intended to to by patients with type 2 diabetes. The implemented in the study patients who were being by their to providing and their in their The results of the study that decreased by that the were In a total of patients with type 2 diabetes and to years were to current treatment therapy HbA1c blood pressure <120 mg/dL mg/dL in those with a of cardiovascular or to treatment aimed at more control therapy HbA1c blood pressure mg/dL mg/dL in those with a of cardiovascular of years, the of the study were by in the therapy while this was not from that in the therapy but were by after for all such as smoking compared to that in the therapy The JDCP study was a large-scale study of Japanese patients with type 1 and type 2 diabetes. The study was conducted to the risk factors for that they develop during The JDCP study a total of patients, years of who were being at between and The of the study the of and in the of the study are currently being reviewed by the involved in the A large-scale to be in an to patients with diabetes are being currently and diabetic complications may as a as well as to improved diabetes care and with these in a large-scale has been since as a between the Japan Diabetes Society and the for Global and the of diabetes education the of a total of and other have in the with the of patients registered some of or more patients have type 1 diabetes. 1

PURPOSE: Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery. PATIENTS AND METHODS: In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n = 420) or prospective validation set (n = 315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay. RESULTS: In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer. CONCLUSION: In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.

This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to mLSG15, a dose-intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T-cell leukaemia-lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15-plus-mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33-71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16-55%) and 75%, respectively. Grade ≥ 3 treatment-emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15-plus-mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15-plus-mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

BACKGROUND: The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific. AIMS/METHODS: To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry. RESULTS: We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients (69 %) were symptomatic. The majority of them (n = 463) presented with acute metabolic crisis during (n = 220) or after the newborn period (n = 243) frequently demonstrating impaired consciousness, vomiting and/or muscular hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency, unexpectedly low in male OTC deficiency, and least frequently in GA1 and female OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency (male and female), hyperammonemia was more severe in metabolic crises during than after the newborn period, whereas metabolic acidosis tended to be more severe in MMA and PA patients with late onset of symptoms. Symptomatic patients without metabolic crises (n = 94) often presented with a movement disorder, mental retardation, epilepsy and psychiatric disorders (the latter in UCD only). CONCLUSIONS: The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis.

Images of breath-hold MR cholangiopancreatography (MRCP) using HASTE (half-Fourier acquisition single-shot turbo spin-echo) sequences were taken in healthy volunteers. The technique was then evaluated as a noninvasive alternative to direct cholangiopancreatography in patients with pancreaticobiliary diseases. Forty healthy volunteers and 56 patients with various pancreaticobiliary diseases were examined by MRCP using HASTE with 128 echo train lengths on a 1.5-T MR unit. A body phased-array coll was used for data collection. Imaging times were 2 sec for the single-slice technique with a 20-mm slice thickness and 18 sec for sequential acquisition by the multislice technique with a 5-mm slice thickness (effective TE, 87 msec). We used the healthy volunteers to determine our ability to detect normal structures. The results obtained by HASTE for both patient groups were correlated with imaging by percutaneous transhepatic cholangiography or endoscopic retrograde cholangiopancreatography. In all healthy volunteers, HASTE-MRCP showed both the common bile duct and the main pancreatic duct. Cystic ducts were visualized in 88% of these volunteers by HASTE-MRCP, and branches of pancreatic ducts were visualized in 75% by HASTE-MRCP. The diameter and length of dilated or stenotic ducts seen on HASTE-MRCP were correlated with percutaneous transhepatic cholangiography or endoscopic retrograde cholangiopancreatography images in 56 diseased patients. Not only the position of stenosis or dilatation but also the distal portion of the stenosis was visualized by HASTE-MRCP. Breath-hold HASTE-MRCP with a phased-array multicoil consistently allows for high-quality images of both normal and diseased pancreaticobiliary tracts. This technique can be used as a noninvasive screening method for pancreaticobiliary diseases in the majority of patients.

INTRODUCTION: Recent accumulating evidence indicates a crucial involvement of macrophage lineage in the pathogenesis of systemic sclerosis (SSc). To analyze the assembly of the monocyte/macrophage population, we evaluated the expression of CD163 and CD204 and various activated macrophage markers, in the inflammatory cells of the skin and in the peripheral blood mononuclear cells (PBMCs) derived from patients with SSc. METHODS: Skin biopsy specimens from 6 healthy controls and 10 SSc patients (7 limited cutaneous SSc and 3 diffuse cutaneous SSc) were analyzed by immunohistochemistry using monoclonal antibody against CD68 (pan-macrophage marker), CD163 and CD204. Surface and/or intracellular protein expression of CD14 (marker for monocyte lineage), CD163 and CD204 was analysed by flow cytometry in PBMCs from 16 healthy controls and 41 SSc patients (26 limited cutaneous SSc and 15 diffuse cutaneous SSc). Statistical analysis was carried out using Mann-Whitney U test for comparison of means. RESULTS: In the skin from SSc patients, the number of CD163+ cells or CD204+ cells between the collagen fibers was significantly larger than that in healthy controls. Flow cytometry showed that the population of CD14+ cells was significantly greater in PBMCs from SSc patients than that in healthy controls. Further analysis of CD14+ cells in SSc patients revealed higher expression of CD163 and the presence of two unique peaks in the CD204 histogram. Additionally, we found that the CD163+ cells belong to CD14brightCD204+ population. CONCLUSIONS: This is the first report indicating CD163+ or CD204+ activated macrophages may be one of the potential fibrogenic regulators in the SSc skin. Furthermore, this study suggests a portion of PBMCs in SSc patients abnormally differentiates into CD14brightCD163+CD204+ subset. The subset specific to SSc may play an important role in the pathogenesis of this disease, as the source of CD163+ or CD204+ macrophages in the skin.

Background: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous “more versus less statins” trials. However, no clear evidence for more versus less statins has been established in an Asian population. Methods: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) &lt;120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. Results: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P &lt;0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; P =0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73–0.93; P =0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (&lt;95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. Conclusions: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01042730.

Abstract Gut dysbiosis caused by antibiotics impairs response to immune checkpoint blockade (ICB). Gut microbiota is becoming an attractive therapeutic target for cancer. The Clostridium butyricum MIYAIRI 588 strain is a probiotic therapy used to improve symptoms related to antibiotic-induced dysbiosis in Japan. We hypothesized that probiotic Clostridium butyricum therapy (CBT) may affect the therapeutic efficacy of ICBs. We retrospectively evaluated 118 patients with advanced non–small cell lung cancer treated with ICBs at Kumamoto University Hospital (Kumamoto-shi, Kumamoto, Japan). Survival analysis comparing patients given CBT before and/or after ICB was conducted using univariate analyses and Cox proportional hazards regression models using propensity score. Propensity score analyses confirmed that probiotic CBT significantly prolonged progression-free survival (PFS) and overall survival (OS). Probiotic CBT significantly associated with longer PFS and OS even in patients who received antibiotic therapy. This study suggests that probiotic CBT may have a positive impact on therapeutic efficacy of ICB in patients with cancer. See articles by Hakozaki et al., p. 1243, and Peng et al., p. 1251

BACKGROUND: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. AIMS: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. RESULTS: Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. CONCLUSIONS: Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

Purpose: To test whether our proposed denoising approach with deep learning-based reconstruction (dDLR) can effectively denoise brain MR images.

UNLABELLED: The Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) was recently shown to be a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We evaluated the ability of WFA+-M2BP to predict the development of hepatocellular carcinoma (HCC) in patients who were infected with the hepatitis C virus (HCV). A total of 707 patients who had been admitted to our hospital with chronic HCV infection without other potential risk factors were evaluated to determine the ability of WFA+-M2BP to predict the development of HCC; factors evaluated included age, sex, viral load, genotypes, fibrosis stage, aspartate and alanine aminotransferase levels, bilirubin, albumin, platelet count, alpha-fetoprotein (AFP), WFA+-M2BP, and the response to interferon (IFN) therapy. Serum WFA+-M2BP levels were significantly increased according to the progression of liver fibrosis stage (P<0.001). In each distinctive stage of fibrosis (F0-F1, F2, F3, and F4), the risk of development of HCC was increased according to the elevation of WFA+-M2BP. Multivariate analysis identified age>57 years, F4, AFP>20 ng/mL, WFA+-M2BP ≥4, and WFA+-M2BP 1-4 as well as the response to IFN (no therapy vs. sustained virological response) as independent risk factors for the development of HCC. The time-dependent areas under the receiver operating characteristic curve demonstrated that the WFA+-M2BP assay predicted the development of HCC with higher diagnostic accuracy than AFP. CONCLUSION: WFA+-M2BP can be applied as a useful surrogate marker for the risk of HCC development, in addition to liver biopsy.

AIMS: To compare the occurrence of cerebral, cardiovascular, and renal events in patients with hyperuricaemia treated with febuxostat and those treated with conventional therapy with lifestyle modification. METHODS AND RESULTS: This multicentre, prospective, randomized open-label, blinded endpoint study was done in 141 hospitals in Japan. A total of 1070 patients were included in the intention-to-treat population. Elderly patients with hyperuricaemia (serum uric acid >7.0 to ≤9.0 mg/dL) at risk for cerebral, cardiovascular, or renal disease, defined by the presence of hypertension, Type 2 diabetes, renal disease, or history of cerebral or cardiovascular disease, were randomized to febuxostat and non-febuxostat groups and were observed for 36 months. Cerebral, cardiovascular, and renal events and all deaths were defined as the primary composite event. The serum uric acid level at endpoint (withdrawal or completion of the study) in the febuxostat (n = 537) and non-febuxostat groups (n = 533) was 4.50 ± 1.52 and 6.76 ± 1.45 mg/dL, respectively (P < 0.001). The primary composite event rate was significantly lower in the febuxostat group than in non-febuxostat treatment [hazard ratio (HR) 0.750, 95% confidence interval (CI) 0.592-0.950; P = 0.017] and the most frequent event was renal impairment (febuxostat group: 16.2%, non-febuxostat group: 20.5%; HR 0.745, 95% CI 0.562-0.987; P = 0.041). CONCLUSION: Febuxostat lowers uric acid and delays the progression of renal dysfunction. REGISTRATION: ClinicalTrials.gov (NCT01984749).

PURPOSE: To reduce radiation dose from abdominal computed tomography (CT) without degradation of low-contrast detectability by using a technique with low tube voltage (90 kV). MATERIALS AND METHODS: The institutional review board approved the participation of the radiologists in the observer performance test, and informed consent was obtained from all participating radiologists. A phantom for measurement of the radiation dose and a phantom containing low-contrast objects were scanned with a 16-detector row CT scanner at 120 kV and 90 kV. For determination of the radiation dose at both 90 kV and 120 kV, the tube current-time product settings were 100-560 mAs, and the doses at the center and periphery of the phantom were measured. To assess low-contrast detectability, we used a 300-mAs setting at 120 kV and 250-560-mAs settings at 90 kV. Five observers participated in the receiver operating characteristic analysis. Area under the receiver operating characteristic curve (A(z)) values were calculated in each observer. A(z) values obtained with each of the scanning techniques were recorded, and differences were examined for significance by using the Dunnet method. RESULTS: The mean A(z) value was 0.951 at 120 kV and 300 mAs. A(z) values were 0.927-0.973 at 90 kV and 450-560 mAs, and the differences between those values and values obtained at 120 kV and 300 mAs were not significant (P = .937-.952). A value of 100% was assigned to the radiation dose delivered to the center of the phantom at 120 kV and 300 mAs. The relative dose delivered at 90 kV ranged from 65% at 450 mAs to 79% at 560 mAs. CONCLUSION: A reduction from 120 kV to 90 kV led to as much as a 35% reduction in the radiation dose, without sacrifice of low-contrast detectability, at CT.

The purpose of this study was to determine the relationship between the apparent diffusion coefficient (ADC) and diffuse renal disease by diffusion-weighted echolanar magnetic resonance (MR) imaging (EPI). Thirty-four patients were examined with diffusion-weighted EPI. The average ADC values were 2.55 x 10(-3) mm2/sec for the cortex and 2.84 x 10(-3) mm2/sec for the medulla in the normal kidneys. The ADC values in both the cortex and medulla in chronic renal failure (CRF) kidneys and in acute renal failure (ARF) kidneys were significantly lower than those of the normal kidneys. In renal artery stenosis kidneys, the ADC values in the cortex were significantly lower than those of the normal and the contralateral kidneys. In the cortex, ADC values were above 1.8 x 10(-3) mm2/sec in all 32 normal kidneys, ranging from 1.6 to 2.0 x 10(-3) mm2/sec in all 8 ARF kidneys, and below 1.5 x 10(-3) mm2/sec in 14 of 15 CRF kidneys. In the medulla, there was considerable overlap in the ADC values of the normal and diseased kidneys. There was a linear correlation between ADC value and sCr level in the cortex (r = 0.75) and a weak linear correlation in the medulla (r = 0.60). Our results show that diffusion-weighted MR imaging may be useful to identify renal dysfunction.