[Paclitaxel plus Bevacizumab Therapy plus Surgical Resection Results in Local Control of Stage â ¢C Breast Cancer].

The case was a 40-year-old female who was aware of a right breast mass for 1 year before her first visit. She had visited her previous doctor because the mass was gradually increasing in size. After close examination, she was diagnosed with Stage ⅢC triple-negative breast cancer. She underwent 4 courses of EC therapy and 7 courses of paclitaxel(PTX)plus bevacizumab( Bev)therapy and was then, referred to our hospital for resection. We instituted a 2-month break from Bev to prevent postoperative complications. She underwent a right mastectomy, combined chest wall resection, lymph node dissection, and chest wall reconstruction. Because the postoperative course was good and quality of life improved, the multidisciplinary treatment with surgery and pharmacotherapy was considered effective in locally advanced breast cancer.

Nuss procedure for pectus excavatum in a patient with cleidocranial dysplasia.

Cleidocranial dysplasia is an autosomal skeletal disorder resulting from delayed or abnormal ossification of bony growth. Pectus excavatum independently presented in a 9-year-old boy with cleidocranial dysplasia and was corrected using the Nuss procedure. There were no perioperative complications, and the post-operative course was uneventful. Although there were concerns regarding extraordinary late consolidation or remodeling of the bony thorax, placement of a Nuss plate for 5 years and 6 months improved the patient's concave deformity without re-depression.

Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial.

BACKGROUND: Limited evidence suggests that multifactorial interventions for control of glucose, blood pressure, and lipids reduce macrovascular complications and mortality in patients with type 2 diabetes. However, safe and effective treatment targets for these risk factors have not been determined for such interventions. METHODS: In this multicentre, open-label, randomised, parallel-group trial, undertaken at 81 clinical sites in Japan, we randomly assigned (1:1) patients with type 2 diabetes aged 45-69 years with hypertension, dyslipidaemia, or both, and an HbA1c of 6·9% (52·0 mmol/mol) or higher, to receive conventional therapy for glucose, blood pressure, and lipid control (targets: HbA1c <6·9% [52·0 mmol/mol], blood pressure <130/80 mm Hg, LDL cholesterol <120 mg/dL [or 100 mg/dL in patients with a history of coronary artery disease]) or intensive therapy (HbA1c <6·2% [44·3 mmol/mol], blood pressure <120/75 mm Hg, LDL cholesterol <80 mg/dL [or 70 mg/dL in patients with a history of coronary artery disease]). Randomisation was done using a computer-generated, dynamic balancing method, stratified by sex, age, HbA1c, and history of cardiovascular disease. Neither patients nor investigators were masked to group assignment. The primary outcome was occurrence of any of a composite of myocardial infarction, stroke, revascularisation (coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting), and all-cause mortality. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00300976. FINDINGS: Between June 16, 2006, and March 31, 2009, 2542 eligible patients were randomly assigned to intensive therapy or conventional therapy (1271 in each group) and followed up for a median of 8·5 years (IQR 7·3-9·0). Two patients in the intensive therapy group were found to be ineligible after randomisation and were excluded from the analyses. During the intervention period, mean HbA1c, systolic blood pressure, diastolic blood pressure, and LDL cholesterol concentrations were significantly lower in the intensive therapy group than in the conventional therapy group (6·8% [51·0 mmol/mol] vs 7·2% [55·2 mmol/mol]; 123 mm Hg vs 129 mm Hg; 71 mm Hg vs 74 mm Hg; and 85 mg/dL vs 104 mg/dL, respectively; all p<0·0001). The primary outcome occurred in 109 patients in the intensive therapy group and in 133 patients in the conventional therapy group (hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·094). In a post-hoc breakdown of the composite outcome, frequencies of all-cause mortality (HR 1·01, 95% CI 0·68-1·51; p=0·95) and coronary events (myocardial infarction, coronary artery bypass surgery, and percutaneous transluminal coronary angioplasty; HR 0·86, 0·58-1·27; p=0·44) did not differ between groups, but cerebrovascular events (stroke, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting) were significantly less frequent in the intensive therapy group (HR 0·42, 0·24-0·74; p=0·002). Apart from non-severe hypoglycaemia (521 [41%] patients in the intensive therapy group vs 283 [22%] in the conventional therapy group, p<0·0001) and oedema (193 [15%] vs 129 [10%], p=0·0001), the frequencies of major adverse events did not differ between groups. INTERPRETATION: Our results do not fully support the efficacy of further intensified multifactorial intervention compared with current standard care for the prevention of a composite of coronary events, cerebrovascular events, and all-cause mortality. Nevertheless, our findings suggest a potential benefit of an intensified intervention for the prevention of cerebrovascular events in patients with type 2 diabetes. FUNDING: Ministry of Health, Labour and Welfare of Japan, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Kissei Pharmaceutical, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Novo Nordisk, Ono Pharmaceutical, Pfizer, Sanwa Kagaku Kenkyusho, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda.

Design of and rationale for the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3): a multicenter, open-label, randomized, parallel-group trial.

OBJECTIVE: Multifactorial intervention including the management of levels of blood glucose (BG), blood pressure (BP), and lipids has been suggested to decrease cardiovascular disease (CVD) risk. However, the target ideal and feasible levels for these individual parameters have not been fully evaluated. In this study, we examine the hypothesis that stricter control compared with the current targets in the Japanese guideline for BG, BP, and lipids could efficiently and safely reduce CVD risk. RESEARCH DESIGN AND METHODS: We screened patients with type 2 diabetes and hypertension and/or dyslipidemia among 81 hospitals in Japan and allocated them into 2 groups: the intensive therapy group (ITG) and the conventional therapy group (CTG). For the 2 respective groups, the target for glycated hemoglobin (HbA1c) is <6.2% (44 mmol/mol) and <6.9% (52 mmol/mol), for BP it is <120/75 mm Hg and <130/80 mm Hg, and for low-density lipoprotein cholesterol it is <80 mg/dL (<70 mg/dL in the presence of CVD history) and <120 mg/dL (<100 mg/dL in the presence of CVD history). The primary end point is the occurrence of CVD events or death by any cause. These patients are scheduled for stepwise intensifications of medication for BG, BP, and lipid control in the ITG, until the number of primary end point events reaches 250. RESULTS: We recruited 2542 patients and randomly allocated 1271 into the ITG and 1271 into the CTG between June 2006 and March 2009. The mean HbA1c was 8.0% (64 mmol/mol) and the mean duration of diabetes was 8.3 years. CONCLUSIONS: This randomized controlled study will test the hypothesis that strict multifactorial intervention therapy is effective for the prevention of CVDs in patients with type 2 diabetes who are at high CVD risk. TRIAL REGISTRATION NUMBER: NCT00300976.

Proanthocyanidins in an astringent persimmon inhibit Salmonella pathogenicity island 1 (SPI1) secretion.

BACKGROUND: Astringent compounds contained in persimmon fruits have been widely used in Japan as food preservatives and thus as anti-bacterial and anti-fungi reagents. However, the molecular mechanism of the anti-microbial activity has been unclear. One of the virulence secretion systems in Salmonella enterica was used to test the anti-microbial activity of extracts from a persimmon (Diospyros kaki Thunb 'Saijo'). RESULTS: We found that the extract could inhibit the secretion of virulence proteins but did not affect cell growth and determined the critical concentrations of the extract to show the effect. Then, the effective fraction on the suppression of secretion of virulence proteins was purified from the crude extracts using solvent partition, absorption chromatography and gel filtration chromatography. The anti-bacterial fraction was analysed by HCl-butanol treatment and gel permeation chromatography followed by nuclear magnetic resonance and identified as the octamers of epigallocatechin and its gallate as major components. CONCLUSION: Proanthocyanidins suppress the secretion of Salmonella pathogenicity island 1 virulence proteins.

[Gender-difference in diabetes mellitus].

Gender-difference is thought to be an important factor in the pathogenesis of glucose metabolism. Imbalances in sex hormones, such as increasing levels of progesterone or testosterone, are associated with systemic insulin resistance. After menopause, women are at an increased risk to develop visceral obesity due to the loss of endogenous ovarian hormone production. On the other hand, insulin resistance caused excess secretion of androgen, leading to menstrual disorder in obese young female. For the better management of glucose intolerance in pregnancy, the diagnostic criteria for gestational diabetes was revised in Japan. Although glucose intolerance in pregnancy is usually recovered after delivery, the subjects who diagnosed gestational diabetes need to be followed for an early detection of type 2 diabetes development. In addition, gender-differences in living practice and attitude are related to their lifestyle, including diet and exercise, therefore, gender-specific medicine increasingly plays key roles in the treatment of diabetes.

Seasonal variation of severe hypoglycemia in hospitalized patients 60 years of age or older presenting to an emergency center hospital between 2004 and 2010.

OBJECTIVE: To investigate the seasonal variation of severe hypoglycemia in hospitalized elderly patients. METHODS: Among the patients hospitalized in our department between 2004 and 2010, we analyzed the records of 67 patients who required emergency admission for severe hypoglycemia and were aged 60 years or older. Comparisons were made between those admitted during the warm season (April-September) and those in the cold season (October-March). PATIENTS: The mean age of the 67 patients was 76±8 years, including 45 men and 22 women. Twenty-four patients were admitted in the warm season and 43 patients were admitted in the cold season, with the average annual number being 3.4±1.9 and 6.1±2.8, respectively (p<0.05). RESULTS: Admissions for patients taking insulin showed no significant difference between the warm and cold season. In contrast, significantly fewer patients taking oral hypoglycemic agents were admitted in the warm season than in the cold season (5 vs. 22, p<0.05). Among them, 26 patients (96%) were taking sulfonylurea, and anorexia associated with acute infections was the main cause of severe hypoglycemia. In the warm season, all of the patients were discharged without complications, while 8 patients had complications in the cold season. CONCLUSION: A seasonal variation regarding hospitalization was observed for severe hypoglycemia among the patients 60 years of age or older, with a higher incidence in the cold season than the warm season, and anorexia related to infections in patients taking sulfonylureas was responsible for this variation. Accordingly, careful management of acute illness is needed for patients using sulfonylureas, especially during the cold season.