Search

We present a new technique for carotid artery reconstruction using a modified bifurcated saphenous vein graft in a patient with a malignant neck tumor. This technique can optimize the size match between the SVG and common carotid artery, as well as the internal and external carotid arteries. Post operative computed tomography performed a year after the operation demonstrated excellent graft alignment and patent carotid arteries., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Binge eating is a characteristic symptom observed in obese individuals that is related to dysfunction of dopaminergic neurons (DNs). Intermittent administration of a high-fat diet (HFD) is reported to induce binge-like eating, but the underlying mechanisms remain unclear. We generated dopaminergic neuron specific IKKβ deficient mice (KO) to examine the effects of inflammation in DNs on binge-like eating under inflammatory conditions associated with HFD. After administration of HFD for 4 weeks, mice were fasted for 24 h, and then the consumption of HFD was measured for 2 h. We also evaluated that the mRNA expressions of inflammatory cytokines, glial markers, and dopamine signaling-related genes in the ventral tegmental area (VTA) and striatum. Moreover, insulin was administered intraventricularly to assess downstream signaling. The consumption of HFD was significantly reduced, and the phosphorylation of AKT in the VTA was significantly increased in female KO compared to wild-type (WT) mice. Analyses of mRNA expressions revealed that DNs activity and inflammation in the VTA were significantly decreased in female KO mice. Thus, our data suggest that HFD-induced inflammation with glial cell activation in the VTA affects DNs function and causes abnormal eating behaviors accompanied by insulin resistance in the VTA of female mice.

Leptin, a hormone secreted by adipocytes, exhibits therapeutic potential for the treatment of type 1 diabetes (T1D). Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme that negatively regulates leptin receptor signaling. Here, the role of PTP1B in the treatment of T1D was investigated using PTP1B-deficient (knockout [KO]) mice and a PTP1B inhibitor. T1D wild-type (WT) mice induced by streptozotocin showed marked hyperglycemia compared with non-T1D WT mice. KO mice displayed significantly improved glucose metabolism equivalent to non-T1D WT mice, whereas peripheral or central administration of leptin partially improved glucose metabolism in T1D WT mice. Peripheral combination therapy of leptin and a PTP1B inhibitor in T1D WT mice improved glucose metabolism to the same level as non-T1D WT mice. Leptin was shown to act on the arcuate nucleus in the hypothalamus to suppress gluconeogenesis in liver and enhance glucose uptake in both brown adipose tissue and soleus muscle through the sympathetic nervous system. These effects were enhanced by PTP1B deficiency. Thus, treatment of T1D with leptin, PTP1B deficiency, or a PTP1B inhibitor was shown to enhance leptin activity in the hypothalamus to improve glucose metabolism. These findings suggest a potential alternative therapy for T1D., (© 2022 by the American Diabetes Association.)

We investigated whether peripheral combination treatment of a sodium-glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptozotocin to produce IDDM. IDDM mice were then divided into five groups: SGLT2 inhibitor treatment alone, leptin treatment alone, leptin and SGLT2 inhibitor co-treatment, untreated IDDM mice, and healthy mice groups. The blood glucose (BG) level at the end of the dark cycle was measured, and a glucose tolerance test (GTT) was performed and compared between the five groups. Leptin was peripherally administered at 20 μg/day using an osmotic pump, and an SGLT2 inhibitor, ipragliflozin, was orally administered at 3 mg/kg/day. Monotherapy with SGLT2 inhibitor or leptin significantly improved glucose metabolism in mice as evaluated by BG and GTT compared with the untreated group, whereas the co-treatment group with SGLT2 inhibitor and leptin further improved glucose metabolism as compared with the monotherapy group. Notably, glucose metabolism in the co-treatment group improved to the same level as that in the healthy mice group. Thus, peripheral combination treatment with leptin and SGLT2 inhibitor improved glucose metabolism in IDDM mice without the use of insulin., Competing Interests: Declaration of competing interest The authors declare that they have no conflict interests., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABA B R) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABA B R-deficient knockout (KO) mice compared to WT mice. Treatment with the GABA B R agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABA B R signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice., (© 2021. The Author(s).)

Objective: To evaluate patient acceptability and bowel preparation efficacy of sodium picosulfate-magnesium citrate (PICOPREP) for colonoscopy., Methods: A questionnaire survey regarding the patient acceptability of bowel preparation agent PICOPREP was administered to 54 patients, and its efficacy was evaluated using the Ottawa Bowel Preparation Scale (OBPS)., Results: Eighteen (33.3%) participants reported that PICOPREP is very easy to drink, 30 (55.5%) easy, four (7.4%) acceptable, one (1.9%) difficult, and one (1.9%) very difficult. The flavor was very good as reported by eight (14.8%) participants, good by 25 (46.3%), neutral by 20 (37.0%), bad by one (1.9%), and very bad by none. The number of patients who requested PICOPREP was 42 (77.7%), indicating its high acceptability. Evaluation of the OBPS score showed that the rectosigmoid colon had significantly better polyethylene glycol (PEG) scores than PICOPREP, but the entire colon did not show a significant difference between PICOPREP and PEG scores (1.09 ± 0.65 vs. 1.17 ± 0.76, p  = 0.632 in the right colon; 0.48 ± 0.52 vs. 0.72 ± 0.66, p  = 0.079 in the mid colon, 0.93 ± 0.49 vs. 0.63 ± 0.52, p  = 0.012 in the rectosigmoid colon, and 3.28 ± 1.70 vs. 3.20 ± 1.90, p  = 0.836 in the entire colon)., Conclusion: PICOPREP is considered as one of the important options due to its good patient acceptability and high efficacy similar to PEG., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The reward system, which consists of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens and caudate-putamen in the striatum, has an important role in the pathogenesis of not only drug addiction but also diet-induced obesity. In the present study, we examined whether signaling through glucocorticoid receptors (GRs) in the reward system affects the rewarding value of a high-fat diet (HFD). To do so, we generated mice that lack functional GRs specifically in dopaminergic neurons (D-KO mice) or corticostriatal neurons (CS-KO mice), subjected the mice to caloric restriction stress conditions, and evaluated the rewarding value of a HFD by conditioned place preference (CPP) test. Caloric restriction induced increases in serum corticosterone to similar levels in all genotypes. While CS-KO as well as WT mice exhibited a significant preference for HFD in the CPP test, D-KO mice exhibited no such preference. There were no differences between WT and D-KO mice in consumption of HFD after fasting or cognitive function evaluated by a novel object recognition test. These data suggest that glucocorticoid signaling in the VTA increases the rewarding value of a HFD under restricted caloric stress.

The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.

Objective We investigated the muscle cramp status of patients with liver cirrhosis by focusing on the degree of liver damage, skeletal muscle mass, and nutritional status. Methods All enrolled patients completed a questionnaire about muscle cramps. The degree of liver damage was examined using the Child-Pugh classification and the albumin-bilirubin (ALBI) grade. The nutritional status and skeletal muscle mass were examined using the Controlling Nutritional Status (CONUT) method and the psoas muscle index (PMI). Results Among the respondents, 55.7% of the patients reported experiencing muscle cramps. An analysis of the two patient groups-those who experienced muscle cramps and those who did not-revealed significant differences in Child-Pugh classification (muscle cramp-positive vs. muscle cramp-negative: A/B/C, 54.1%/32.4%/13.5% vs. 90.0%/10.0%/0.0%; p=0.004), ALBI grade (1/2/3, 20.5%/71.8%/7.7% vs. 54.8%/38.7%/6.5%; p=0.011), modified ALBI grade (1/2a/2b/3, 20.5%/20.5%/51.3%/7.7% vs. 54.8%/22.6%/16.1%/6.5%; p=0.008), CONUT score (normal/mild/moderate/severe, 25.6%/28.2%/41.0%/5.1% vs. 22.6%/61.3%/12.9%/3.2%; p=0.024), and PMI (3.85±1.13 cm 2 /m 2 vs. 4.94±1.86 cm 2 /m 2 ; p=0.012). Conclusion Our findings suggest that muscle cramps occur more frequently in patients with liver cirrhosis due to their decreased liver function and poorer nutritional status.

Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas., Competing Interests: The authors have declared that no competing interests exist.

Background: Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM)., Methods: A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint., Results: Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05)., Conclusions: In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone., Clinical Trials Registration: UMIN000019024., Competing Interests: Competing interests: SI receives personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb, MSD K.K., and Chugai Pharmaceutical Co., Ltd. TO receives personal fees from MSD K.K. HT receives grants from MSD K.K. YI receives grants from Sanwa Kagaku Kenkyusho, Kowa Pharmaceutical, MSD K.K., Dainippon Sumitomo, Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Boehringer Ingelheim, Nihon Medi-Physics Co., Ltd., and personal fees from Astellas Pharma, Daiichi Sankyo, and Ono Pharmaceutical Company. KY receives personal fees from Ono Pharmaceutical Company, MSD K.K., and Bristol-Myers Squibb. TH received personal fees from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Company, and Bristol-Myers Squibb while the study was being conducted. TH also received grants from Boehringer Ingelheim, Taiho Pharmaceutical Co., Ltd., and personal fees from Boehringer Ingelheim outside the submitted work. MMS receives personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb, MSD K.K., and Chugai Pharmaceutical Co., Ltd. MA receives grants from Kyowa Kirin Co., Ltd. YA receives grants and personal fees from Ono Pharmaceutical Company, Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co. Ltd. as well as personal fees from Bristol-Myers Squibb. MA receives grants and personal fees from Ono Pharmaceutical Company, MSD K.K., and personal fees from Bristol-Myers Squibb. YH receives grants and personal fees from Ono Pharmaceutical Company, Chugai Pharmaceutical Co., Ltd., Eli Lilly, Boehringer Ingelheim, Bristol-Myers Squibb, MSD K.K., and Pfizer; grants from Novartis and Taiho Pharmaceutical Co., Ltd., and personal fees from Astra Zeneca. HA receives grants from Ono Pharmaceutical Company, MSD K.K., Chugai Pharmaceutical Co. Ltd., and personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb, and MSD K.K., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The present study aimed to evaluate the effects of flash glucose monitoring (FGM) and conventional self-monitoring of blood glucose (SMBG) on glycemic control in patients with non-insulin-treated type 2 diabetes., Research Design and Methods: In this 24-week, multicenter, open-label, randomized (1:1), parallel-group study, patients with non-insulin-treated type 2 diabetes at five hospitals in Japan were randomly assigned to the FGM (n=49) or SMBG (n=51) groups and were provided each device for 12 weeks. The primary outcome was change in glycated hemoglobin (HbA1c) level, and was compared using analysis of covariance model that included baseline values and group as covariates., Results: Forty-eight participants in the FGM group and 45 in the SMBG group completed the study. The mean HbA1c levels were 7.83% (62.1 mmol/mol) in the FGM group and 7.84% (62.2 mmol/mol) in the SMBG group at baseline, and the values were reduced in both FGM (-0.43% (-4.7 mmol/mol), p<0.001) and SMBG groups (-0.30% (-3.3 mmol/mol), p=0.001) at 12 weeks. On the other hand, HbA1c was significantly decreased from baseline values in the FGM group, but not in the SMBG group at 24 weeks (FGM: -0.46% (-5.0 mmol/mol), p<0.001; SMBG: -0.17% (-1.8 mmol/mol), p=0.124); a significant between-group difference was also observed (difference -0.29% (-3.2 mmol/mol), p=0.022). Diabetes Treatment Satisfaction Questionnaire score was significantly improved, and the mean glucose levels, SD of glucose, mean amplitude of glycemic excursions and time in hyperglycemia were significantly decreased in the FGM group compared with the SMBG group., Conclusions: Glycemic control was better with FGM than with SMBG after cessation of glucose monitoring in patients with non-insulin-treated type 2 diabetes., Trial Registration Number: UMIN000026452, jRCTs041180082., Competing Interests: Competing interests: HA reports grants and speaker honoraria from Abbott Japan outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To compare different configurations of the bilateral internal thoracic arteries for the left coronary system and examine early and late outcomes, including mid-term graft patency., Methods: We reviewed 877 patients who underwent primary isolated coronary artery bypass grafting using in situ bilateral internal thoracic arteries [in situ right internal thoracic artery (RITA)-to-left anterior descending artery (LAD) grafting, n = 683; in situ left internal thoracic artery (LITA)-to-LAD grafting, n = 194]. We compared mid-term patency between the grafts. Propensity score matching was performed to investigate early and long-term outcomes., Results: The 2-year patency rate for RITA-to-LAD and LITA-to-LAD grafts were similar. Multivariate analysis revealed that RITA-to-non-LAD anastomosis (P = 0.029), postoperative length of stay (P = 0.003) and chronic obstructive pulmonary disease (P = 0.005) were associated with graft failure. After statistical adjustment, 176 propensity-matched pairs were available for comparison. RITA-to-LAD grafting enabled a more distal anastomosis. Kaplan-Meier analysis revealed that the incidences of death, repeat revascularization and myocardial infarction were significantly higher in the LITA-to-LAD group among both the unmatched and matched samples (P = 0.045 and 0.029, respectively)., Conclusions: The mid-term patency and outcomes of RITA-to-LAD grafting are good and reduces future cardiac event, in contrast to LITA-to-LAD grafting., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia caused by impairment of arginine vasopressin (AVP) secretion. In this study, we evaluated plasma AVP concentrations during a hypertonic saline infusion test using a new AVP radioimmunoassay (RIA) which is now available in Japan. Thirteen control subjects, mostly with hypothalamo-pituitary disease but without CDI, and 13 patients with CDI were enrolled in the study. Whether or not subjects had CDI was determined based on the totality of clinical data, which included urine volumes and osmolality. Regression analysis of plasma AVP and serum Na concentrations revealed that the gradient was significantly lower in the CDI group than in the control group. The area under the receiver-operating-characteristic (ROC) curve was 0.99, and the <0.1 gradient cut-off values for the simple regression line to distinguish CDI from control had a 100% sensitivity and a 77% specificity. The ROC analysis with estimated plasma AVP concentrations at a serum Na concentration of 149 mEq/L showed that the area under the ROC curve was 1.0 and the <1.0 pg/mL cut-off values of plasma AVP had a 99% sensitivity and a 95% specificity. We conclude that measurement of AVP by RIA during a hypertonic saline infusion test can differentiate patients with CDI from those without CDI with a high degree of accuracy. Further investigation is required to confirm whether the cut-off values shown in this study are also applicable to a diagnosis of partial CDI or a differential diagnosis between CDI and primary polydipsia.

Background: Anti-programmed cell death-1 (PD-1) antibodies can cause thyroid dysfunction. However, no predictive biomarkers enabling stratification of thyroid dysfunction risk have been identified., Methods: A total of 209 patients treated with an anti-PD-1 antibody were evaluated for anti-thyroid antibodies at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the visits stopped. Thyroid ultrasonography was performed if the patient was positive for anti-thyroid antibodies at baseline., Results: Of the 209 patients, 19 (9.1%) developed thyroid dysfunction (destructive thyroiditis or hypothyroidism). The cumulative incidence of thyroid dysfunction was significantly higher in patients who were positive vs. negative for anti-thyroid antibodies (15/44 [34.1%] vs. 4/165 [2.4%], p < 0.001). Forty-two patients positive for anti-thyroid antibodies at baseline were divided into two groups according to the presence of an irregular echo pattern. The cumulative incidence of thyroid dysfunction was significantly higher in those with an irregular vs. a regular echo pattern (13/23 [56.5%] vs. 1/19 [5.3%], p = 0.001). None of the patients developed thyroid dysfunction after the initial 24-week period., Conclusions: The risk of thyroid dysfunction induced by anti-PD-1 antibodies can be predicted by evaluation of anti-thyroid antibodies and the thyroid echo pattern at baseline., Trial Registration: UMIN000019024.

Background: Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD., Methods: Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined., Results: In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P < .05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r = .42, P = .05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L)., Conclusion: The d-ROMs test may provide a useful indicator of nAMD in men but not in women.

Type 2 diabetes and dyslipidemia are diseases that collectively increase the risk of patients developing cardiovascular complications. Several incretin-based drugs are reported to improve lipid metabolism, and one of these medications, anagliptin, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been shown to decrease serum triglyceride and low-density lipoproteins cholesterol. This study aimed to conduct an investigation into the effects of anagliptin on serum lipid profiles. This multicenter, open-label, randomized (1:1), parallel group study was designed to evaluate the effects of anagliptin on serum lipid profiles (triglycerides, lipoproteins, apolipoproteins, and cholesterol fractions). The study involved 24 patients with type 2 diabetes at two participating hospitals for a period of 24 weeks. Patients were randomly assigned to the anagliptin (n = 12) or control (n = 12) groups. Patients in the anagliptin group were treated with 200 mg of the drug twice daily. Patients in the control group did not receive anagliptin, but continued with their previous treatment schedules. Lipid metabolism was examined under fasting conditions at baseline and 24 weeks. Patients treated with anagliptin for 24 weeks exhibited significantly reduced levels of serum apolipoprotein B-48, a marker for lipid transport from the intestine, compared with the control group patients (P < 0.05). After 24 weeks of treatment, serum adiponectin levels were significantly raised, whereas glycated hemoglobin (HbA1c) levels were significantly lower compared with the baseline in the anagliptin group (P < 0.05), but not in the control group. This study showed that the DPP-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels, suggesting that this drug may have beneficial effects on lipid metabolism possibly mediated by the inhibition of intestinal lipid transport., Competing Interests: Yoshiaki Morishita, Yusuke Seino, and Yoji Hamada belonged to the Department of Metabolic Medicine, which was established by a donation from the Sanwa Kagaku Co. Ltd. Yoshihiro Ito belongs to the Department of Nephrology/CKD initiatives, which receives donations from the Sanwa Kagaku Co. Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The pituitary is a major hormone center that secretes systemic hormones responding to hypothalamus-derived-releasing hormones. Previously, we reported the independent pituitary induction and hypothalamic differentiation of human embryonic stem cells (ESCs). Here, a functional hypothalamic-pituitary unit is generated using human induced pluripotent stem (iPS) cells in vitro. The adrenocorticotropic hormone (ACTH) secretion capacity of the induced pituitary reached a comparable level to that of adult mouse pituitary because of the simultaneous maturation with hypothalamic neurons within the same aggregates. Corticotropin-releasing hormone (CRH) from the hypothalamic area regulates ACTH cells similarly to our hypothalamic-pituitary axis. Our induced hypothalamic-pituitary units respond to environmental hypoglycemic condition in vitro, which mimics a life-threatening situation in vivo, through the CRH-ACTH pathway, and succeed in increasing ACTH secretion. Thus, we generated powerful hybrid organoids by recapitulating hypothalamic-pituitary development, showing autonomous maturation on the basis of interactions between developing tissues., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Binge eating could contribute to the development of obesity, and previous studies suggest that gamma-aminobutyric acid (GABA) type B receptor (GABA B R) signaling is involved in the regulation of binge eating. Here, we show that time-restricted access to a high-fat diet (HFD) induces binge-like eating behavior in wild-type mice. HFD consumption during restricted time was significantly increased in corticostriatal neuron-specific GABA B R-deficient mice compared with wild-type mice. Furthermore, the GABA B R agonist baclofen suppressed HFD intake during restricted time in wild-type mice but not in corticostriatal or dopaminergic neuron-specific GABA B R-deficient mice. In contrast, there were no significant differences in food consumption among genotypes under ad libitum access to HFD. Thus, our data show that the mesolimbic system regulates food consumption under time-restricted but not ad libitum access to HFD and have identified a mechanism by which GABA B R signaling suppresses binge-like eating of HFD., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

High differentiation efficiency is one of the most important factors in developing an in vitro model from pluripotent stem cells. In this report, we improved the handling technique applied to mouse-induced pluripotent stem (iPS) cells, resulting in better differentiation into hypothalamic vasopressin (AVP) neurons. We modified the culture procedure to make the maintenance of iPS cells in an undifferentiated state much easier. Three-dimensional floating culture was demonstrated to be effective for mouse iPS cells. We also improved the differentiation method with regards to embryology, resulting in a greater number of bigger colonies of AVP neurons differentiating from mouse iPS cells. Fgf8, which was not used in the original differentiation method, increased iPS differentiation into AVP neurons. These refinements will be useful as a valuable tool for the modeling of degenerative disease in AVP neurons in vitro using disease-specific iPS cells in future studies., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Based on the hypothesis that silicone oil (SO) with a higher refractive index than water induces unexpected vignetting effects during surgeries, we aimed to investigate the relationship between the volume of SO and light intensity using a surgical microscope., Methods: Using a light-sensitive paper and model eye filled with varying volumes (0%, 50%, 62.5%, 75%, 87.5% and 100%) of SO, the light intensity of intraocular lens (IOL) with various refractive powers (0, 10 and 20 dioptres) illuminated by a surgical microscope was measured., Results: Light exposure density with 1.0% coaxial and oblique light was approximately 22-fold higher than that with 0.1% coaxial and oblique light. Further, it was approximately 34-fold higher in eyes with +20 D IOL than in those with no IOL. The density in eyes with 75% SO was the highest among all groups followed by that with 0% SO. Light exposure densities in the eyes with 75% and 0% SO were significantly higher than those with other volumes of SO. In SO-filled eyes, a microscope set with only an oblique light and a filter successfully reduced light exposure., Conclusion: Silicone oil-related vision loss (SORVL) during SO removal surgeries might be due to increased light exposure on the macular retina caused by the SO-associated vignetting effect. SORVL could be prevented by placing a filter in the microscope during SO removal surgeries., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral tanycytes. They highly expressed tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ tanycyte-like cells from mESCs [induced tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool., (Copyright © 2019 Endocrine Society.)

Background: This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 m Tc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 m Tc-tetrofosmin/stress 201 Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols., Conclusions: The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.

The traditional classification of hypertensive retinopathy was based on the Keith-Wagener-Barker (KWB) grading, which is a subjective scaling system, and it is difficult to distinguish between the first and second grades. Retinal and choroidal vasculatures are affected by systemic hypertension, although retinal vasculature changes with age, axial length, intraocular pressure, and retinal diseases. It is necessary to establish a new objective method to assess hypertensive vascular changes. In the present study, we have examined the vasculature of the macular choriocapillaris in order to establish a new objective method to assess hypertensive vascular changes using optical coherence tomography angiography (OCTA). Choriocapillaris vessel density (VD), vessel length, and vessel diameter index in a 3 × 3 mm macular area were measured by OTCA in a total of 567 volunteers (361 healthy subjects and 206 subjects with systemic hypertension) who attended a basic health check-up. Ocular factors, systemic factors, and medications were evaluated. We detected significant differences in normative choriocapillaris vasculature between the left and right eyes in 53 healthy subjects and revealed correlations between age, intraocular pressure, axial length, and choriocapillaris vasculature in 308 healthy subjects. Normative foveal VD was correlated with age only and the efficiency was weak. The analysis of 206 right eyes (KWB grade 0, 159 eyes; grade 1, 35 eyes; and grade 2, 12 eyes) revealed that foveal VD was strongly correlated with KWB grade only (P < 0.001). This is the first report suggesting that OCTA for foveal choriocapillaris measurement by OCTA would might provide the advantage of evaluating be objective method for evaluating the progression of systemic hypertension.

Context: Immune checkpoint inhibitors, including anti-programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies., Objective: This study examined the incidence of endocrine irAEs induced by nivolumab., Patients and Main Outcome Measured: Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks., Results: Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti-thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions., Conclusions: Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.

Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the "sub-silicone oil fluid (SOF)", enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like choroidal neovascularization and a branching vascular network. Intravitreal aflibercept injection (IAI) or photodynamic therapy (PDT) is used for treatment. We retrospectively compared the 1-year outcomes of IAI monotherapy and its combination with initial PDT for PCV. Twelve eyes with naïve PCV received three IAIs and a single PDT after the first IAI and as needed injection (combination group); 11 eyes with naïve PCV received three IAIs and as needed injections (IAI group). Significant improvements in visual acuity after 2 months and in CRT after 1 month were maintained at 12 months in both groups (both P < 0.05); groups did not differ significantly at any time point. CCT significantly reduced after 3 and 12 months in the combination group (both P < 0.05) but not in the IAI group. A mean of 3.7 ± 0.9 and 5.6 ± 2.0 injections was administered to the combination and IAI groups, respectively (P = 0.013). Within a 1-year period, combination therapy was found to yield similar visual acuity and retinal structure improvements and maintenance as IAI monotherapy while requiring fewer IAIs.

Objectives: To identify factors that determine early saphenous vein graft failure (VGF) within 1 month after coronary artery bypass grafting (CABG)., Methods: Seven hundred forty-nine consecutive patients underwent primary isolated CABG with saphenous vein grafts at three Japanese centres from 1 January 2005 to 31 December 2014. According to angiographic findings within 1 month of CABG surgery, 63 patients (8.4%) developed early VGF. We examined the relationships between variables and early VGF by using multivariable logistic regression analysis., Results: The preoperative clinical characteristics were similar between patients with and without early VGF, except for median preoperative haemoglobin A1c levels, which were significantly higher among patients with early VGF (6.7 vs 6.4%, P = 0.046). Additionally, anastomosis to the vessel with chronic total obstruction was performed more frequently among patients with early VGF (22/63 [34.9%] vs 140/686 [20.4%], P = 0.007), and myocardial infarction during the hospital admission occurred more frequently among patients with early VGF (4/63 [6.3%] vs 2/686 [0.3%], P < 0.0001). Results of multivariable analysis showed that the preoperative haemoglobin A1c level was associated with early VGF (odds ratio per unit increase, 1.30; 95% confidence interval, 1.06-1.60; P = 0.013)., Conclusions: An increased preoperative haemoglobin A1c level was strongly associated with early VGF after CABG. Thus, VGF happened more frequently in patients with poorly controlled diabetes mellitus., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNFα led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries., Competing Interests: The authors have declared that no competing interests exist.

Purpose. We had earlier reported positive hsa-miR-148a-3p expression in eyes with rhegmatogenous retinal detachment (RRD) and its involvement in the epithelial-mesenchymal transition of retinal pigment epithelium in vitro. Here we investigated the association of hsa-miR-148a-3p expression levels in the vitreous fluid of patients with RRD with severity of RRD. Methods. The hsa-miR-148a-3p expression levels in the vitreous fluid, range (degree) of retinal detachment (RD), and pixels of retinal break were measured in 27 eyes with RRD. The association of hsa-miR-148a-3p expression levels with other factors was evaluated by multiple regression analysis. Results. The hsa-miR-148a-3p expression levels, time from onset of RRD to vitrectomy, range of RD, and pixels of retinal breaks were 23.68 ± 43.00, 12.07 ± 15.36 days, 155.85 ± 86.67 degrees, and 37000 ± 67100 pixels, respectively. Five eyes with RRD had vitreous hemorrhage preoperatively. The hsa-miR-148a-3p expression levels were significantly associated with pixels of retinal breaks ( β = 0.699) and the time from onset of RRD to vitrectomy ( β = 0.358) but not with the range of RD or presence of vitreous hemorrhage. Conclusion. The hsa-miR-148a-3p expression levels in the vitreous fluid were significantly associated with the size of retinal break and disease duration., Competing Interests: The authors declare that they have no competing interests.

Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

To evaluate, using pupillography, the difference between eyes affected by age-related macular degeneration and their contralateral normal eyes with regard to the mean relative afferent pupillary defect (RAPD) score. Also, to ascertain any correlations between this difference in RAPD score and differences in visual acuity or age-related macular degeneration (AMD) dimensions. Measurements were made using the RAPDx pupillographer (Konan Medical, Nishinomiya, Japan), which analyzes pupil response to light stimulation. Both best corrected visual acuity (converted to logMAR) and greatest linear dimension (GLD; calculated on the basis of fluorescence angiography images) were measured. The correlations between RAPD difference and logMAR difference, and GLD difference were then analyzed. The study included 32 patients (18 men, 14 women; mean age = 74.8 ± 9.7 years) who had AMD in 1 eye and a normal fundus in the contralateral eye. Mean resting pupil diameter, mean latency onset of constriction, mean velocity of constriction, and recovery were not significantly different in AMD eyes compared with normal eyes. The mean amplitude of constriction was smaller (P = 0.028), and the mean latency of maximum constriction was shorter (P = 0.0013) in AMD eyes than in normal eyes. Regarding RAPD scores, there was a significant correlation between visual acuity difference and RAPD score differences of both amplitude (P < 0.001, r = 0.53) and latency (P = 0.034, r = 0.33). GLD difference was also significantly correlated with differences in both amplitude (P = 0.021, r = 0.36) and latency (P = 0.033, r = 0.33) scores. RAPD outcomes were correlated with visual acuity and AMD dimension. Automated pupillography may be a useful tool in monitoring the progression of AMD and assessing changes in retinal function that result from novel interventions., Competing Interests: The authors report no conflicts of interest.

Purpose: The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro., Methods: Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT)., Results: MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays., Conclusions: The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

Background: Echocardiographic parameters to predict pulmonary capillary wedge pressure (PCWP) in mitral regurgitation (MR) are not yet elucidated. We reported that PCWP could be accurately estimated by novel KT index which is defined as log10[left atrial (LA) emptying function (EF)/LA volume]. We examined the usefulness of the KT index as a predictor of PCWP in primary and secondary MR with sinus rhythm and also MR with atrial fibrillation., Methods: LA dimension, strain, volume, EF, and E/e' were measured in moderate to severe MR with sinus rhythm (n=58, age: 67±8 years) and MR with atrial fibrillation (n=24, age: 69±11 years) just before catheterization and in normal subjects (n=26, age: 67±11 years) using speckle tracking echocardiography. MR with sinus rhythm was divided into primary MR (n=27) and secondary MR (n=31). The estimated PCWP (ePCWP) was calculated as 10.8-12.4×KT index., Results: There was a correlation between PCWP and LA dimension, E/e', minimum LA volume index, active LAEF, total LAEF, or LA strain (r=0.32, r=0.31, r=0.55, r=-0.61, r=-0.51, and r=-0.50, respectively, p<0.05). The better correlation was found between PCWP and ePCWP in MR including both primary and secondary MR and also MR with atrial fibrillation (r=0.70, r=0.67, and r=0.58, respectively, p<0.01). Multiple regression analysis revealed that ePCWP was an independent predictor of PCWP in MR. The ePCWP demonstrated good diagnostic accuracy (area under the curve of 0.86) and sensitivity (81%) and specificity (71%) to predict elevated PCWP >15mmHg using a cut-off of 16mmHg., Conclusion: The ePCWP was the reliable echocardiographic parameter to predict PCWP in primary and secondary MR and might also be useful in MR with atrial fibrillation. The ePCWP may have an incremental value in a clinical setting., (Copyright © 2015. Published by Elsevier Ltd.)

Purpose . It is a matter of increasing concern that exposure to light-emitting diodes (LED), particularly blue light (BL), damages retinal cells. This study aimed to investigate the retinal pigment epithelium (RPE) damage caused by BL and to elucidate the role of nuclear factor (erythroid-derived)-related factor 2 (Nrf2) in the pathogenesis of BL-induced RPE damage. Methods . ARPE-19, a human RPE cell line, and mouse primary RPE cells from wild-type and Nrf2 knockout ( Nrf2 -/- ) mice were cultured under blue LED exposure (intermediate wavelength, 450 nm). Cell death rate and reactive oxygen species (ROS) generation were measured. TUNEL staining was performed to detect apoptosis. Real-time polymerase chain reaction was performed on NRF2 mRNA, and western blotting was performed to detect Nrf2 proteins in the nucleus or cytoplasm of RPE cells. Results . BL exposure increased cell death rate and ROS generation in ARPE-19 cells in a time-dependent manner; cell death was caused by apoptosis. Moreover, BL exposure induced NRF2 mRNA upregulation and Nrf2 nuclear translocation in RPE. Cell death rate was significantly higher in RPE cells from Nrf2 -/- mice than from wild-type mice. Conclusions . The Nrf2 pathway plays an important role in protecting RPE cells against BL-induced oxidative stress.

Minocycline, a derivative of tetracycline, is a broad-spectrum antibiotic used in the treatment of various infections. Black discolouration of the skin, teeth, bones and the thyroid gland are sequelae of long-term minocycline therapy. We report an unusual case of minocycline-induced pigmentation of the aortic valve and sinuses of Valsalva., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Giant bilateral atria with mitral and tricuspid regurgitation can cause postoperative respiratory dysfunction. In this article, we describe a case of giant atria with poor respiratory function that was improved by atrial volume reduction. A 79-year-old woman was referred to our institution for valve surgery. Her vital capacity was 1,080 mL. The mitral and tricuspid valves were repaired during surgery. We removed a circular section of the left atrial wall. The right atrial wall and interatrial septum were removed; this improved her vital capacity to 1,370 mL. We conclude that aggressive volume reduction of both atria improves respiratory function., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A wide and redundant prolapse of the posterior mitral leaflet in active infective endocarditis cannot be easily repaired. A sliding plasty can be attempted, but the range of annular plication is often too large. Chordal replacement is another option, but is prone to long-term degeneration because the redundant leaflet still exists. Here, we describe a simple resection technique that utilizes only two small triangular resections. The resections are sutured with no need to shorten the annulus. The leaflet tissue between the two triangular resections must be preserved to make an appropriately shaped posterior leaflet.

Objectives: We examined the impact of the bioresorbable osteosynthesis sternal pin (Super Fixsorb 30) on sternal healing after median sternotomy., Methods: Sixty-three patients who underwent aortic surgery through median sternotomy between January 2006 and March 2009 were analysed. Sternal pins were utilized in 36 patients in addition to the standard closure of the sternum with Ethibond sutures (Group A), and 27 patients received no pins with the standard Ethibond sternal closure (Group B). The occurrence of transverse sternal dehiscence, anterior-posterior displacement and complete fusion of the sternum were evaluated by a computed tomography scan. The cross-sectional cortical bone density area (CBDA) of the sternum was examined to evaluate the osteoconductivity of the sternal pin over a 12-month period., Results: There was no sternal displacement (0%) observed in Group A at discharge. Meanwhile, five displacements (18.5%) were observed in Group B (P = 0.007). The complete sternal fusion rates at 12 months postoperatively were 100% in Group A, and 21.6% in Group B (P < 0.001). A significant increase in the CBDA was observed in Group A (P < 0.001; between CBDA at discharge and 12 months postoperatively)., Conclusions: The Super Fixsorb 30 sternal pin reduced an anterior-posterior sternal displacement and facilitated an earlier sternal fusion. The pin may have the potential to promote osteogenesis.

A 58-year-old woman was referred to our hospital because of liver dysfunction. Her serum levels of AST (619 IU/l) and ALT (603 IU/l) had increased. Histological findings in the liver biopsy were compatible to autoimmune hepatitis (AIH), and the diagnosis of AIH was confirmed by the diagnostic criteria. She was admitted to a nearby hospital 3 years ago, and diagnosed with Graves' disease. She received methimazole (MMI) at first, which was discontinued due to liver injury in one month, then propylthiouracil (PTU) was administered. One year later, transaminase increased and was decreased by stopping PTU administration. PTU was restarted after her transaminase decreased, but a recurrence of hepatotoxicity was observed, and she was referred to our hospital. Oral prednisolone decreased liver function immediately. In this case, PTU-induced liver injury was suspected as a possible trigger of AIH. While PTU remains a commonly used drug in the treatment of hyperthyroidism, severe liver injury is reported in some cases. If liver injury is observed in patients treated with PTU, rechallenge is not recommended in order to avoid severe hepatotoxicity.

Background: The aim of this study was to evaluate the early and long-term results of a composite valve graft root replacement for various aortic root diseases., Methods: Between 1978 and 2005, 273 patients with various disorders of the aortic root underwent a composite valve graft root replacement. The mean age of the patients was 47.5 +/- 13.2 years. There were 93 patients with Marfan syndrome, 56 aortitis, and 63 type A aortic dissections. Thirty-nine emergency operations and 55 redo operations were included. For the proximal anastomosis, a skirted technique was used in 157 patients. For the coronary reconstruction, Bentall's original inclusion technique was utilized in 36 patients, a direct button technique in 159, and a graft interposition technique in 63. The mean follow-up was 106 months., Results: The in-hospital mortality was 9.5%. An emergency operation emerged as a significant predictor of early death. The actuarial survival rate was 87.0% and 72.9% at 5 and 15 years, respectively. The age at the operation, aortitis, Marfan syndrome, and use of a standard proximal anastomosis emerged as independent determinants of late death. The actuarial reoperation free rate was 96.3% and 89.7% at 5 and 15 years, respectively. In the patients who underwent the skirted technique the incidence of late graft detachment was less frequent than that of the standard technique., Conclusions: A composite valve graft root replacement is a safe and reliable procedure for various aortic root diseases with stable early- and long-term results. The skirted technique seems to be attractive to avoid late graft detachment even in cases with a fragile inflammatory pathology.