Potential clinical benefits of warfarin in end-stage cancers: A retrospective analysis.

Background and Aims: Coagulopathy and thromboembolism are common comorbidities in cancer, and anticoagulants, such as warfarin, are needed in specific situations. This study aimed to determine the clinical relevance of prothrombin time (PT) monitoring and the clinical usefulness of warfarin in patients with malignancy. Methods: We retrospectively investigated patients with PT lower than 10% treated in our hospital between April 2006 and March 2013. Cases of false coagulopathy, including those due to technical errors during blood sampling, were excluded. The cause of coagulopathy was determined or estimated by physicians. Results: This study included 338 cases comprising 155 females and 183 males with a median age was 68 (0-97) years. Among them, 89 (26.3%) had cancer, and 163 (48.2%) received warfarin at a median dose of 2.23 (0.5-8.0) mg/day. PT prolongation caused by warfarin overdose and malignancy exacerbation were observed in 75 (22.2%) and 64 (18.9%) patients, respectively. The leading reasons for warfarin administration were arterial fibrillation, chronic heart failure, and deep vein thrombosis. Univariate analysis revealed that the overall survival was higher in the warfarin and nononcology groups than in the nonwarfarin and oncology groups (both p < 0.001). In multivariate analysis, survival was significantly decreased in older adults (p = 0.049), those with malignancy (p < 0.001), and those without warfarin therapy (p < 0.001). Early mortality (within 3 days after PT prolongation) was observed in 65 patients and was mostly related to emergent diseases (36.9%, 24/65) and end-stage malignancy (32.3%, 21/65). Conclusion: Patients with malignancy may experience subclinical PT prolongation upon disease progression. Warfarin treatment mitigates panic PT values in patients with malignancy. Conversely, those not treated with warfarin have poor survival, suggesting that coagulopathy without warfarin treatment can lead to death. Warfarin enhances hemostatic conditions, thereby preventing malignancy-related lethal hemorrhagic or thromboembolic events.

[Mitral Valve Regurgitation Exacerbated by Aortic Dissection:Report of a Case].

The patient was a 74-year-old woman who was originally followed up for hypertrophic cardiomyopathy and mitral regurgitation without subjective symptoms. With the onset of acute aortic dissection, the mitral regurgitation was exacerbated with systolic anterior motion. In addition to aortic dissection surgery, mitral valve surgery was performed. The mitral valve was approached through a right-sided left atrial incision and replaced with a bioprosthetic valve. For aortic dissection, ascending aortic replacement was performed. The postoperative course was uneventful, and the patient was discharged on foot after rehabilitation. Simultaneous mitral valve surgery for acute aortic dissection is rare, but by intervening simultaneously, we were able to achieve a favorable postoperative course.

Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of lateral epicondylitis of the humerus - Secondary publication.

BACKGROUND: The guidelines presented herein provide recommendations for the management of patients with lateral epicondylitis of the humerus. These recommendations are endorsed by the Japanese Orthopaedic Association (JOA) and Japan Elbow Society. METHODS: The JOA lateral epicondylitis guideline committee revised the previous guidelines on the basis of the "Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014", which emphasized the importance of the balance between benefit and harm, and proposed a desirable method for preparing clinical guidelines in Japan. These guidelines consist of 11 clinical questions (CQs), 9 background questions (BQs), and 3 future research questions (FRQs). For each CQ, outcomes from the literature were collected and evaluated systematically according to the adopted study design. RESULTS: The committee proposed recommendations for each CQ by determining the level of evidence and assessing the consensus rate. Physical therapy was the best recommendation with the best evidence. The BQs and FRQs were answered by collecting evidence based on the literature. CONCLUSIONS: The guidelines presented herein were reviewed systematically, and recommendations were proposed for each CQ. These guidelines are expected to be widely used not only by surgeons or physicians but also by other healthcare providers, such as nurses, therapists, and athletic trainers.

Endovascular rescue for malpositioned frozen elephant trunk into the false lumen.

We describe a case of frozen elephant trunk deployment unintentionally malpositioned into the false lumen. An 83-year-old man underwent total arch repair with a frozen elephant trunk for type A acute aortic dissection complicated by mesenteric malperfusion. However, intraoperative transesophageal echocardiography showed expansion of the false lumen in the descending aorta, suggesting a malpositioned frozen elephant trunk into the false lumen. Endovascular fenestration of the dissecting flap and subsequent endograft deployment from the inside of the malpositioned frozen elephant trunk graft to the true lumen of the descending aorta was successfully performed under intravascular ultrasound guidance.

[Traction-assisted Negative Pressure Wound Therapy for Pediatric Poststernotomy Mediastinitis:Report of Two Cases].

We herein report two cases of pediatric poststernotomy mediastinitis treated by traction-assisted negative pressure wound therapy (NPWT) with Zip Surgical Skin Closure (Zip), which is a non-invasive skin closure device. We used this device with NPWT in cases of pediatric poststernotomy mediastinitis to stabilize the sternum and reduce the natural retractive forces of the skin. The patients were two boys (two and three months old), with an onset of infection at 13 and eight postoperative days, respectively. The culture examination detected methicillin-susceptible Staphylococcus aureus in both cases. Traction-assisted NPWT with Zip was performed at-75 mmHg for 16 and 33 days, and the wounds healed completely. In conclusion, this modification was successfully applied to treat pediatric poststernotomy mediastinitis and may help reduce the duration of treatment.

Chronic contained rupture of abdominal aortic aneurysm that developed from chronic abdominal aortic dissection.

A chronic contained rupture is an extremely rare subtype of abdominal aortic aneurysm rupture. We report the case of a 59-year-old man with a medical history of traumatic lumber fracture 7 years ago. He presented to us with an asymptomatic irregular abdominal aortic aneurysm, and surgery was performed 1 week after he was hospitalized. Based on the medical history, imaging, blood tests, and pathologic results, we determined that the chronic contained rupture progressed from a localized abdominal aortic dissection. This case illustrates the need to follow the morphology of aortic aneurysms if chronic abdominal aortic dissection is observed.

[Adhesion Prevention Effect of Circular Pericardial Drainage].

Pericardial adhesions can pose serious problems during cardiac reoperation. Here, we report three cases where circular pericardial drainage (CPD) was performed during the initial surgery and no pericardial adhesions were found during reoperation. All three patients had initially undergone an aortic valve replacement with CPD. Case 1:An 80-year-old female was reoperated this time for an aneurysm of the ascending aorta. A replacement of the ascending aorta was performed. Case 2:A 76-year-old male underwent a second aortic valve repair indicated for prosthetic valve infection. Case 3:The patient was an 82-year-old female. This time, mitral valve replacement, indicated for severe mitral valve stenosis, was performed. In these three cases, there were almost no adhesions in the CPD route. The diaphragmatic pericardial surface, the oblique sinus of pericardium, and the lateral side of the left ventricle were also adhesion-free. CPD can effectively drain postoperative pericardial hemorrhage and thus prevent pericardial adhesions.

Effects of bilirubin configurational photoisomers on the measurement of direct bilirubin by the vanadate oxidation method.

BACKGROUND: Direct-reacting bilirubin concentrations measured using vanadate chemical oxidation method do not exactly match the conjugated bilirubin concentration. One of the causes is the effect of bilirubin photoisomers. However, the quantitative evaluation of the effects of these photoisomers has not been sufficiently conducted. In particular, the influence of bilirubin configurational isomers on direct bilirubin is the most critical factor. METHODS: Sixteen residual serum samples were used. For quantitative analysis based on the change in direct bilirubin and bilirubin configurational isomer, samples were irradiated via blue light-emitting diodes to suppress the production of bilirubin structural isomers. Total bilirubin and direct bilirubin concentrations were measured using the vanadate chemical oxidation method. Concentrations of 4Z,15Z-bilirubin IXα and its photoisomers were measured using high-performance liquid chromatography. The sum of 4Z,15E-bilirubin IXα and 4E,15Z-bilirubin IXα was notated as bilirubin configurational isomer, and the differences between the measured values of the irradiated and non-irradiated samples were calculated and notated as ΔDB and ΔBCI. RESULTS: In non-irradiated and irradiated samples, total bilirubin and direct bilirubin concentrations were 10.73 mg/dL with significant a decrease to 10.60 mg/dL and 0.69 mg/dL with a significant increase to 0.78 mg/dL, while bilirubin configurational isomer values were 1.00 mg/dL and 1.52 mg/dL, respectively. The linear regression equation revealed a significant positive correlation of Y = 0.187X-0.006 between ΔDB (Y) and ΔBCI (X). CONCLUSION: Applying the vanadate chemical oxidation method affected approximately 19% of the bilirubin configurational isomer concentration for direct bilirubin. Extreme caution is necessary when interpreting the measured values of samples indicative of unconjugated hyperbilirubinaemia.

[Thoracic Endovascular Repair for Chronic Aortic Dissection with Aberrant Origin of the Left Vertebral Artery;Report of a Case].

We herein report a case of thoracic endovascular aortic repair( TEVAR) for chronic aortic dissection with an aberrant left vertebral artery( LVA) originating from the aortic arch. A 51-year-old man with a medical history of Stanford type B acute aortic dissection 2 years ago was transferred to our institution for the treatment of an aortic expansion. Computed tomography showed a large entry just distal to the takeoff of the left subclavian artery and a dilated dissected thoracic aorta. A left cervical incision over the anterior border of the sternocleidomastoid was made, and the LVA was identified. The proximal LVA was ligated and anastomosed to the left common carotid artery in an end-to-side fashion. After completion of the carotid-subclavian bypass, TEVAR was performed in the usual fashion. The postoperative course was uneventful without stroke or spinal cord injury. At the 1-year follow-up, the false lumen had shrunk and the LVA remained patent.

[Tricuspid Valve Replacement Preserving the Leaflets in a Congenitally Corrected Transposition of the Great Arteries;Report of a Case].

In patients with a congenitally corrected transposition of the great arteries (ccTGA), the regurgitation of the systemic atrioventricular valve (SAVV) increases and anatomical right ventricular (ARV) dysfunction often progressively develops. A low systemic ventricular ejection fraction( SVEF) is a risk factor for mortality. However, in patients with a low ejection fraction of ARV, it is unclear how to best perform valve replacement for patients with regurgitation of SAVV. A 70-year-old female with respirator discomfort was admitted to our hospital and diagnosed to have situs solitus ccTGA, severe SAVV regurgitation, and ARV dysfunction. Her ARV ejection fraction was 25% and she was therefore dependent on inotropic agents. We successfully performed a tricuspid valve replacement while preserving the leaflets, the chorda tendineae's, and papillary muscles, and placing the lead for cardiac resynchronization therapy on the ARV. Her postoperative course was uneventful. Thereafter, she was discharged 6 weeks after surgery.

Multiple graft injury due to migrated nonbroken sternal wires 2 years after cardiac surgery.

The migration of sternal wires into vital structures is a rare but potentially life-threatening complication and associated with infection in some cases. While a few cases have been reported the sternal wires were broken in those cases. To our knowledge, this is the first report of multiple, nonbroken, migrated sternal wires stabbing vascular grafts.

Intervention using behavior modification techniques to improve the lifestyle of high-risk metabolic syndrome patients.

[Purpose] The present study examined the effects of a 12-week intervention combined with behavior modification techniques to improve the lifestyle and biochemical indicators, of high-risk metabolic syndrome patients. [Participants and Methods] The 21 participants (10 participants in the intervention group and 11 participants in the control group) were provided with information about metabolic syndrome. Participants in the intervention group were asked to set goals to improve their lifestyle (dietary and exercise) and their self-efficacy. The participants completed and submitted a weekly, self-monitoring sheet and were provided with feedback on their lifestyle. [Results] Following intervention, the values of body mass index and abdominal circumference were significantly lower for the intervention group as compared to the control group. There were no differences in the total physical activity level, total energy intake, or blood levels of lipids between the two groups. [Conclusion] According to Motivational Interviewing, to modify and continue behaviors, it is important for people to recognize "their significance" and have "confidence". In the present study, information about metabolic syndrome was provided to enable the recognition of the importance of behaviors. Moreover, participants in the intervention group were required to set goals to increase their self-efficacy. We attribute the participants' weight loss and decrease in abdominal circumference to this.

Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy.

Objective: The chronic kidney disease (CKD) is widely diagnosed on the basis of albuminuria and the glomerular filtration rate. A more precise diagnosis of CKD, however, requires the assessment of other factors. Urinary adiponectin recently attracted attention for CKD assessment, but evaluation is difficult due to the very low concentration of urinary adiponectin in normal subjects. Research design and methods: We developed an ultrasensitive ELISA coupled with thionicotinamide-adenine dinucleotide cycling to detect trace amounts of proteins, which allows us to measure urinary adiponectin at the subattomole level. We measured urinary adiponectin levels in 59 patients with diabetes mellitus (DM) and 24 subjects without DM (normal) to test our hypothesis that urinary adiponectin levels increase with progression of CKD due to DM. Results: The urinary adiponectin levels were 14.88±3.16 (ng/mg creatinine, mean±SEM) for patients with DM, and 3.06±0.33 (ng/mg creatinine) for normal subjects. The threshold between them was 4.0 ng/mg creatinine. The urinary adiponectin levels increased with an increase in the CKD risk. Furthermore, urinary adiponectin mainly formed a medium-molecular weight multimer (a hexamer) in patients with DM, whereas it formed only a low-molecular weight multimer (a trimer) in normal subjects. That is, the increase in urinary adiponectin in patients with DM led to the emergence of a medium-molecular weight form in urine. Conclusions: Our new assay showed that urinary adiponectin could be a new diagnostic index for CKD. This assay is a non-invasive test using only urine, thus reducing the patient burden.

Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice.

Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.

Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection.

BACKGROUND: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4 index, and AST to platelet ratio index (APRI) based on histopathological analysis of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV) infection. METHODS: Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores were calculated using preserved serum samples. The fibrosis staging and activity grading were assessed using a modified METAVIR score. RESULTS: A total of 122 patients were enrolled; the cohort included 27 patients with stage 1, 66 with stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four fibrosis biomarkers presented AUC values greater than 0.8. Each of the four biomarkers in stage 2 was significantly different between the activity grade 1 and 2 groups. CONCLUSION: Fib-4 index and APRI were comparable with WFA-M2BP and ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with HCV infection. All four biomarkers of liver fibrosis were influenced by histopathological activity grading, which implies that liver biopsy should be the gold standard to evaluate liver fibrosis staging even though several noninvasive biomarkers have been investigated well.

GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose.

Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance. These effects are blunted by vagotomy or pharmacological GLP-1R blockade, and by genetic inactivation of GLP-1R signaling in whole body or selectively in vagal afferents. Our results identify D-allulose as prominent GLP-1 releaser that acts via vagal afferents to restrict feeding and hyperglycemia. Furthermore, when administered in a time-specific manner, chronic D-allulose corrects arrhythmic overeating, obesity and diabetes, suggesting that chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.

Fish oil and fenofibrate inhibit pancreatic islet hypertrophy, and improve glucose and lipid metabolic dysfuntions with different ways in diabetic KK mice.

We examined the effects of fish oil and fenofibrate (FF) on the pancreatic islet hypertrophy, and on the modification of glucose and lipid metabolic dysfunctions in KK mice with insulin resistance. The mice were fed one of four diets [25en% lard/safflower oil (LSO), 25en% fish oil (FO), or each of these diets plus 0.1wt% FF (LSO/FF, FO/FF)] for 9 weeks. FO group and both FF groups had significantly lower final body and adipose tissue weights than LSO group. Pancreatic islet hypertrophy was observed only in LSO group but not in the other groups with fish oil or FF. And, it is likely that fish oil has a stronger therapeutic effect on islet hypertrophy. Plasma adiponectin level was significantly higher in FO group but not in both FF groups. Expression of hepatic lipogenic enzyme genes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) was lower in FO groups with or without FF, whereas fatty acid oxidation-related mRNAs such as acyl-CoA oxidase (AOX) and uncoupling protein-2 (UCP-2) were more abundant in FF groups with or without fish oil. Our results suggest that both fish oil and FF improve pancreatic islet hypertrophy with the amelioration of insulin resistance. Fish oil enhances insulin sensitivity by increasing plasma adiponectin; however, the beneficial effect of FF on insulin resistance seems to be independent of the plasma adiponectin level. These results mean that improvement of glucose and lipid metabolic dysfuctions in diabetic KK mice are independently approached by fish oil and FF.

Correlation between serum galectin-9 levels and liver fibrosis.

BACKGROUND AND AIM: Chronic liver diseases progress from chronic inflammation to fibrosis to tumorigenesis. Galectin-9, a ß-galactoside-specific animal lectin, is indicated to contribute to all three steps of progression. The aim of this study was to determine which of the three steps was most dominant in elevating the serum galectin-9 concentration and to test the possibility of galectin-9 as a serum biomarker. METHODS: Japanese patients with chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC), non-alcoholic fatty liver disease, or alcoholic liver disease who provided informed consent were enrolled in this study. Serum galectin-9 levels were measured using a sandwich ELISA. Multiple regression analyses were performed using ezr to identify factors that determined serum galectin-9 concentration. RESULTS: One hundred one patients with 50 of chronic hepatitis and 51 of liver cirrhosis were enrolled; the cohort included 45 cases of hepatitis C virus infection, 13 cases of hepatitis B virus infection, and 46 cases with HCC-related complications. The median serum galectin-9 concentration was 77.54 pg/mL (interquartile range: 18.89-241.9 pg/mL). Multiple linear regression analyses proved Fibrosis-4 index and aspartate aminotransferase to platelet ratio index, indexes of liver fibrosis, were able to predict the serum galectin-9 levels with statistical significance. A multiple logistic regression analysis determined 10 pg/mL increase in the serum galectin-9 concentration presented an odds ratio of 3.90 for liver fibrosis progression. CONCLUSIONS: The serum galectin-9 concentration represents a potential biomarker of liver fibrosis in patients with chronic liver diseases, regardless of chronic inflammation or the presence of HCC complications. Furthermore, higher serum galectin-9 levels are a predictor for liver fibrosis progression.

Effects of bilirubin photoisomers on the measurement of direct bilirubin by the bilirubin oxidase method.

Background We occasionally encounter increases in direct bilirubin value on reanalysis of the surplus serum collected in the past from a neonate with indirect hyperbilirubinemia. But the details of this phenomenon are unclear. We evaluated the change of direct bilirubin and the relation of bilirubin photoisomer of the serum exposed to room light. Methods Surplus serum samples from neonates with indirect hyperbilirubinemia were exposed to room light for 24 h. The bilirubin fraction assay of samples was performed by the bilirubin oxidase method (Nescauto and Aqua-auto Kainos reagent) and high-performance liquid chromatography. Results Direct bilirubin increased significantly from 0.61 to 2.36 mg/dL. The respective ratios of bilirubin photoisomers before and after exposure were as follows: cyclobilirubin (0.007 to 0.29) and (EZ)-bilirubin (0.018 to 0.041) increased significantly, (ZZ)-bilirubin decreased 0.84 to 0.55 significantly. The difference of the cyclobilirubin concentration was most closely associated with those of the direct bilirubin concentration. Conclusion Direct bilirubin value was increased after exposure to the room light, and increase in direct bilirubin was significantly correlated by cyclobilirubin increase in the serum samples from neonates with indirect hyperbilirubinemia.

Chemical Design and Example of Transparent Bipolar Semiconductors.

Transparent bipolar semiconductors (TBSCs) are in demand for transparent electronics to serve as the basis for next generation optoelectronic devices. However, the poor carrier controllability in wide-bandgap materials makes the realization of a bipolar nature difficult. Only two materials, CuInO2 and SnO, have been reported as TBSCs. To satisfy demand for the coexistence of transparency and bipolarity, we propose a design concept with three strategies; choice of early transition metals (eTM) such as Y3+ and Zr4+ for improving controllability of carrier doping, design of chemical bonds to obtain an appropriate band structure for bipolar doping, and use of a forbidden band-edge transition to retain transparency. This approach is verified through a practical examination of a candidate material, tetragonal ZrOS, which is chosen by following the criteria. ZrOS exhibits an excellent controllability of the electrical conductivity (10-7-10-2 S cm-1), p- or n-type nature with ∼10-2 S cm-1 by Y or F doping, respectively, and optically wide gap (below 10-4 cm-1 up to ∼2.5 eV). This concept provides a new kind of TBSC based on eTM ionic compounds.