Effects of Exercise Training on Mitochondrial Fatty Acid ß-Oxidation in the Kidneys of Dahl Salt-Sensitive Rats.

Exercise training (Ex) has anti-hypertensive and renal protective effects. In this study, we investigate the effects of Ex on mitochondrial fatty acid metabolism in the kidneys of Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS) diet. Eight-week-old, male Dahl-S rats were divided into three groups: (1) normal-salt diet, sedentary (NS-Sed), (2) HS diet, sedentary (HS-Sed), and (3) HS-Ex. The NS and HS groups were fed a diet containing 0.6% and 8% NaCl, respectively. The HS-Ex group performed treadmill running for 8 weeks (5 days/week; 60 min/day at 16-20 m/min, 0% gradient). Renal function and the expression of enzymes and regulators of ß-oxidation and electron transport chain (ETC) complexes were assessed. HS increased systolic blood pressure and proteinuria, and Ex ameliorated these defects. HS also reduced creatinine clearance, and Ex ameliorated it. HS reduced the renal expression of enzymes of ß-oxidation (carnitine palmitoyltransferase type I (CPTI) and acyl-CoA dehydrogenases (CADs)) and the related transcription factors peroxisome proliferator-activated receptor α (PPARα) and PPARγ-coactivator-1α (PGC-1α), and Ex restored this. HS also reduced the renal expression of enzymes in ETC complexes, and Ex restored this expression. Ex ameliorates HS-induced renal damage by upregulating enzymes involved in fatty acid ß-oxidation and ETC complexes via increases in PPAR-α and PGC-1α expressions in the kidneys of Dahl-S rats. These results suggest that Ex may have beneficial effects on HS-induced mitochondrial dysfunction in the kidney.

Exercise Training Prevents High Fructose-Induced Hypertension and Renal Damages in Male Dahl Salt-Sensitive Rats.

INTRODUCTION: High-fructose diet (HFr) causes metabolic syndrome, and HFr-induced hypertension and renal damage are exaggerated in Dahl salt-sensitive (DS) rats. Exercise training (Ex) has antihypertensive and renal protective effects in rats fed HFr; however, there has been little discussion about the DS rats, which exhibit metabolic disturbances. This study thus examined the effects of Ex on DS rats fed HFr. METHODS: Male DS rats were divided into three groups. The control group was fed a control diet, and both the HFr group and the HFr-Ex group were fed an HFr (60% fructose). The HFr-Ex group also underwent treadmill running (20 m·min -1 , 60 min·d -1 , 5 d·wk -1 ). After 12 wk, renal function, histology, and renin-angiotensin system were examined. RESULTS: HFr increased blood pressure, urinary albumin, and creatinine clearance, and Ex inhibited these increases. HFr induced glomerular sclerosis, podocyte injury, afferent arteriole thickening, and renal interstitial fibrosis, and Ex ameliorated them. HFr reduced plasma renin activity, and Ex further reduced the activity. HFr also increased the expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor, and Ex restored the ACE expression to the control levels. HFr decreased the expression of ACE2, angiotensin II type 2 receptor, and Mas receptor, and Ex restored the ACE2 and Mas receptor expressions to the control levels and further decreased the angiotensin II type 2 receptor expression. HFr increased the ACE activity and decreased the ACE2 activity, and Ex restored these activities to the control levels. CONCLUSIONS: Ex prevents HFr-induced hypertension and renal damages in DS rats. The changes in renal renin-angiotensin system may be involved in the mechanism of the antihypertensive and renal protective effects of Ex.

Supporting Shared Decision-making About Surveillance After Breast Cancer With Personalized Recurrence Risk Calculations: Development of a Patient Decision Aid Using the International Patient Decision AIDS Standards Development Process in Combination With a Mixed Methods Design.

BACKGROUND: Although the treatment for breast cancer is highly personalized, posttreatment surveillance remains one-size-fits-all: annual imaging and physical examination for at least five years after treatment. The INFLUENCE nomogram is a prognostic model for estimating the 5-year risk for locoregional recurrences and second primary tumors after breast cancer. The use of personalized outcome data (such as risks for recurrences) can enrich the process of shared decision-making (SDM) for personalized surveillance after breast cancer. OBJECTIVE: This study aimed to develop a patient decision aid (PtDA), integrating personalized risk calculations on risks for recurrences, to support SDM for personalized surveillance after curative treatment for invasive breast cancer. METHODS: For the development of the PtDA, the International Patient Decision Aids Standards development process was combined with a mixed methods design inspired by the development process of previously developed PtDAs. In the development, 8 steps were distinguished: establishing a multidisciplinary steering group; definition of the end users, scope, and purpose of the PtDA; assessment of the decisional needs of end users; defining requirements for the PtDA; determining the format and implementation strategy for the PtDA; prototyping; alpha testing; and beta testing. The composed steering group convened during regular working-group sessions throughout the development process. RESULTS: The "Breast Cancer Surveillance Decision Aid" consists of 3 components that support the SDM process: a handout sheet on which personalized risks for recurrences, calculated using the INFLUENCE-nomogram, can be visualized and which contains an explanation about the decision for surveillance and a login code for a web-based deliberation tool; a web-based deliberation tool, including a patient-reported outcome measure on fear of cancer recurrence; and a summary sheet summarizing patient preferences and considerations. The PtDA was assessed as usable and acceptable during alpha testing. Beta testing is currently ongoing. CONCLUSIONS: We developed an acceptable and usable PtDA that integrates personalized risk calculations for the risk for recurrences to support SDM for surveillance after breast cancer. The implementation and effects of the use of the "Breast Cancer Surveillance Decision Aid" are being investigated in a clinical trial.

Development of an online patient decision aid for kidney failure treatment modality decisions.

BACKGROUND: Patient decision aids (PtDAs) support patients and clinicians in shared decision-making (SDM). Real-world outcome information may improve patients' risk perception, and help patients make decisions congruent with their expectations and values. Our aim was to develop an online PtDA to support kidney failure treatment modality decision-making, that: 1) provides patients with real-world outcome information, and 2) facilitates SDM in clinical practice. METHODS: The International Patient Decision Aids Standards (IPDAS) development process model was complemented with a user-centred and convergent mixed-methods approach. Rapid prototyping was used to develop the PtDA with a multidisciplinary steering group in an iterative process of co-creation. The results of an exploratory evidence review and a needs-assessment among patients, caregivers, and clinicians were used to develop the PtDA. Seven Dutch teaching hospitals and two national Dutch outcome registries provided real-world data on selected outcomes for all kidney failure treatment modalities. Alpha and beta testing were performed to assess the prototype and finalise development. An implementation strategy was developed to guide implementation of the PtDA in clinical practice. RESULTS: The 'Kidney Failure Decision Aid' consists of three components designed to help patients and clinicians engage in SDM: 1) a paper hand-out sheet, 2) an interactive website, and 3) a personal summary sheet. A 'patients-like-me' infographic was developed to visualise survival probabilities for each treatment modality on the website. Other treatment outcomes were incorporated as event rates (e.g. hospitalisation rates) or explained in text (e.g. the flexibility of each treatment modality). No major revisions were needed after alpha and beta testing. During beta testing, some patients ignored the survival probabilities because they considered these too confronting. Nonetheless, patients agreed that every patient has the right to choose whether they want to view this information. Patients and clinicians believed that the PtDA would help patients make informed decisions, and that it would support values- and preferences-based decision-making. Implementation of the PtDA has started in October 2020. CONCLUSIONS: The 'Kidney Failure Decision Aid' was designed to facilitate SDM in clinical practice and contains real-world outcome information on all kidney failure treatment modalities. It is currently being investigated for its effects on SDM in a clinical trial.

Effects of Exercise Training on the Renin-Angiotensin System in the Kidneys of Dahl Salt-Sensitive Rats.

PURPOSE: Exercise training (Ex) has antihypertensive and renal protective effects; however, the precise mechanisms remain unclear. The renal renin-angiotensin system (RAS) plays a vital role in renal function and pathology. Therefore, we investigated the effects of Ex on the renal RAS components in Dahl salt-sensitive (Dahl-S) rats. METHODS: Male Dahl-S rats were divided into four groups: normal salt diet + sedentary, normal salt diet + Ex, high-salt diet (HS, 8% NaCl) + sedentary, and HS + Ex. Treadmill running was performed for 8 wk in the Ex groups. RESULTS: Ex attenuated the HS-induced renal dysfunction and glomerular injury without causing blood pressure alterations. HS increased urinary excretion of both total and intact angiotensinogen. Ex decreased the HS-induced increased urinary excretion of total angiotensinogen. However, it did not change the HS-induced urinary excretion of intact angiotensinogen, indicating reduced intact angiotensinogen cleaving. Ex restored the HS-induced increased angiotensinogen and angiotensin II type 1 receptor expressions in the outer medulla and the HS-induced increased angiotensin-converting enzyme expression in the cortex. Ex restored the HS-induced decreased renin expression in the cortex and outer medulla, and the HS-induced decreased angiotensin-converting enzyme 2, angiotensin II type 2 receptor, and Mas receptor expressions in the outer medulla. CONCLUSIONS: Ex attenuates HS-induced renal dysfunction, glomerular injury, and renal RAS dysregulation in Dahl-S rats.

Febuxostat ameliorates high salt intake-induced hypertension and renal damage in Dahl salt-sensitive rats.

OBJECTIVE: Several clinical studies have reported that xanthine oxidoreductase inhibitors have antihypertensive and renal protective effects but their mechanisms have not been fully determined. This study aims to clarify these mechanisms by examining the effects of febuxostat, which is a novel selective xanthine oxidoreductase inhibitor, in Dahl salt-sensitive rats. METHODS: Eight-week-old male Dahl salt-sensitive rats were fed a normal salt (0.6% NaCl) or high salt (8% NaCl) diet for 8 weeks. A portion of the rats that were fed high salt diet were treated with febuxostat (3 mg/kg per day) simultaneously. Additionally, acute effects of febuxostat (3 mg/kg per day) were examined after high salt diet feeding for 4 or 8 weeks. RESULTS: Treatment with febuxostat for 8 weeks attenuated high salt diet-induced hypertension, renal dysfunction, glomerular injury, and renal interstitial fibrosis. Febuxostat treatment reduced urinary excretion of H2O2 and malondialdehyde and renal thiobarbituric acid reactive substances content. High salt diet increased xanthine oxidoreductase activity and expression in the proximal tubules and medullary interstitium. Febuxostat completely inhibited xanthine oxidoreductase activity and attenuated the high salt diet-increased xanthine oxidoreductase expression. Febuxostat transiently increased urine volume and Na+ excretion without change in blood pressure or urinary creatinine excretion after high salt diet feeding for 4 or 8 weeks. CONCLUSION: Febuxostat ameliorates high salt diet-induced hypertension and renal damage with a reduction of renal oxidative stress in Dahl salt-sensitive rats. The antihypertensive effect of febuxostat may be mediated in part by diuretic and natriuretic action.

Erucic Acid-Rich Yellow Mustard Oil Improves Insulin Resistance in KK-Ay Mice.

Obesity is a major risk factor for some metabolic disorders including type 2 diabetes. Enhancement of peroxisome proliferator-activated receptor (PPAR) γ, a master regulator of adipocyte differentiation, is known to increase insulin-sensitive small adipocytes. In contrast, decreased PPARγ activity is also reported to improve insulin resistance. We have previously identified erucic acid as a novel natural component suppressing PPARγ transcriptional activity. In this study, we investigated the effect of erucic acid-rich yellow mustard oil (YMO) on obese/diabetic KK-Ay mice. An in vitro luciferase reporter assay and mesenchymal stem cell (MSC) differentiation assay revealed that 25 µg/mL YMO significantly inhibited PPARγ transcriptional activity and differentiation of MSCs into adipocytes but promoted their differentiation into osteoblasts. In KK-Ay mice, dietary intake of 7.0% (w/w) YMO significantly decreased the surrogate indexes for insulin resistance and the infiltration of macrophages into adipose tissue. Furthermore, 7.0% YMO increased bone mineral density. These results suggest that YMO can ameliorate obesity-induced metabolic disorders.

Erucic acid derived from rosemary regulates differentiation of mesenchymal stem cells into osteoblasts/adipocytes via suppression of peroxisome proliferator-activated receptor γ transcriptional activity.

Osteoporosis is associated with increase in fat tissue in bone marrow in humans. Mesenchymal stem cells in bone marrow are induced to differentiate into osteoblasts rather than adipocytes by the stimulation of peroxisome proliferator-activated receptor (PPAR) γ antagonists. PPARγ antagonists are expected to be useful to prevent osteoporosis by regulating the lineages of mesenchymal stem cells in bone marrow, as well as the prevention of obesity. In this study, we explored natural components suppressing PPARγ transcriptional activity in rosemary. Separation of active fraction of rosemary extract by repeated high performance liquid chromatograph and PPARγ luciferase reporter assay identified erucic acid, one of the monounsaturated fatty acids, as an active component. Twenty-five-micrometer erucic acid significantly decreased PPARγ luciferase activity and enhanced the differentiation of mouse-delivered C3H10T1/2 cells into osteoblasts rather than adipocytes. Furthermore, 25-µM erucic acid significantly decreased the expression of adipocyte marker genes, while accelerating osteoblast marker genes. In conclusion, erucic acid is a novel natural component derived from rosemary regulating mesenchymal stem cell differentiation via suppression of PPARγ transcriptional activity.

Superior outcomes (but at higher costs) of non-operative management with interval appendectomy over immediate surgery in appendicitis with abscess: Results from a large adult population cohort.

INTRODUCTION: The aim of this study was to compare surgical outcomes and hospitalization costs between immediate surgery and non-operative management followed by interval appendectomy in adults presenting with appendicitis with abscess. METHODS: From 2003 to 2015, 3316 patients presented with appendicitis, including 101 who presented with appendicular abscess. Between 2003 and 2006, 33 patients with appendicular abscess were managed with emergency operations (emergency group). Non-operative management followed by interval appendectomy was implemented in 2007 and offered to 68 patients during the study period. Of these patients, 64 patients underwent the procedure (interval group), and 4 patients refused. RESULTS: Non-operative management was successful in 76.6% of cases (49/64 patients) in the interval group. Operative time and length of hospital stay were similar between the emergency and interval groups. In the interval group, blood loss, the need for extended resection, and overall postoperative morbidity were significantly lower than in the emergency group (P < 0.01, respectively). Medical costs for surgery in the interval group were lower than in the emergency group ($4512 vs $6888, P = 0.002), but this group's total medical costs were higher ($9591 vs $6888, P < 0.01). CONCLUSION: The interval strategy is associated with a reduced need for extended resection, lower postoperative morbidity, and a shorter length of hospital stay. However, total medical costs for the interval strategy are higher than those for emergency operations in cases of appendicular abscess in adults.

Prospective short-term feasibility study of perioperative suprapubic catheters in laparoscopic colectomy.

INTRODUCTION: Here we report a prospective study on whether a temporary suprapubic catheter (SPC) can be safely inserted as a substitute for transurethral balloon catheterization during laparoscopy-assisted colectomy. METHODS: Our subjects included 52 cases who gave informed consent to have an SPC inserted. These subjects were selected from cases who underwent laparoscopy-assisted surgery for primary colorectal cancer from October 2014 to August 2015. RESULTS: An SPC was inserted into 45 of the original 52 cases. The median surgical duration was 220 min (range, 11-438 min), and the SPC insertion was performed at a median of 133 min (range, 9-384 min) after the start of surgery. Insertion required a median duration of 116 s. In one case (2.2%), the bladder was perforated by the paracentesis needle, and in two cases (4.4%), hematuria was observed at the time of insertion; however, surgery was completed without any incident in these three cases. Six of the remaining 42 cases (13.3%) demonstrated neither micturition desire nor independent urination on the day the catheter was clamped. In these cases, the clamp was released two to four times, and draining of an average of 586-mL urine, micturition desire, and independent urination were confirmed 2-4 days later. CONCLUSION: Transurethral balloon catheterization is a simple procedure that is commonly used on surgical patients, but it can cause pain, discomfort, and infection. In contrast, SPC insertion is a procedure that avoids crossing the urethra and its associated disadvantages. Here we were able to demonstrate that the procedure can be safely used in laparoscopic surgery patients.

Xanthine Oxidase Inhibitor, Febuxostat Ameliorates the High Salt Intake-Induced Cardiac Hypertrophy and Fibrosis in Dahl Salt-Sensitive Rats.

BACKGROUND: Xanthine oxidase (XO) is a source of reactive oxygen species production in the heart. However, pathophysiological role of XO has not been clarified in hypertensive heart disease. Thus, the present study examined the impacts of high salt (HS) intake and febuxostat (Fx), a XO inhibitor in Dahl salt-sensitive (Dahl-S) rats. METHODS: Eight-week old, male Dahl-S rats were fed a normal salt diet (0.6% NaCl) or a HS diet (8% NaCl) for 8 weeks. A part of the rats fed the HS diet were simultaneously treated with Fx (3 mg/kg/day). RESULTS: HS intake increased blood pressure and heart weight with cardiomyocyte hypertrophy and interstitial fibrosis in the left ventricle (LV), and Fx diminished them. HS increased the XO activity 4.7-fold and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity 1.5-fold, and Fx not only blocked the XO activity but also inhibited the HS-increased NADPH oxidase activity. HS increased the expression of XO, collagen, transforming growth factor-ß1 (TGF-ß1), angiotensin-converting enzyme, and angiotensin II type 1 receptor and the phosphorylation of extracellular signal-regulated kinase (ERK) in the LV, and Fx reduced the expression and phosphorylation of these proteins except XO. CONCLUSIONS: Fx ameliorates the HS intake-induced hypertension, LV hypertrophy, and fibrosis with decreasing the TGF-ß1 expression and ERK phosphorylation in Dahl-S rats. Fx also down-regulates cardiac NADPH oxidase and renin-angiotensin system. The XO inhibition may be an effective therapy for hypertensive heart disease.

[Carcinosarcoma of the Esophagus That Presented as Esophageal Stenosis].

Esophageal carcinosarcoma is a rare malignant tumor. A 76-year-old man consulted near hospital about dysphagia. A gastrointestinal fiberscopy showed a stricture of the thoracic esophagus at approximately 34 cm from the incisor, and the macroscopic type of the tumor was 0-Ip. Biopsy results indicated carcinosarcoma. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. Pathological examination of the surgical specimen revealed that the majority of the tumor was composed of spindle-shaped atypical cells, but because a very small transitional area between squamous cell carcinoma and sarcoma was noted, a diagnosis of carcinosarcoma was made. The depth of invasion was small, and no region lymph node metastasis was detected. We classified the tumor as pT1b(SM)N0M0, pStage I. Immunohistochemically, the spindle-shaped sarcomatous cells displayed a posi- tive reaction to vimentin and cytokeratin AE1/AE3. Ki -67(MIB-1)labeling index was high. The patient was discharged after an uneventful postoperative course and remains well as an outpatient at his 6-month follow-up. We report this case with a review of the literature.

[A Case of Advanced Gastric Cancer with Ptosis Caused by Orbital Metastasis].

Orbital metastasis of gastric cancer occurs very rarely.A 76-year-old woman, who consulted another doctor with the chief complaints of palpitation, shortness of breath, and anorexia 1 month previously, was referred to our clinic for workup and treatment.Workup revealed type III advanced gastric cancer at the lesser curvature of the gastric antrum.Biopsy revealed a diagnosis of poorly differentiated adenocarcinoma.As computed tomography suggested periaortic lymph node metastasis, a diagnosis of T4a(SE)N3aM1(LYM), cStage IV was made.Two weeks later, ptosis was observed in the right eye, and positron emission tomography-computed tomography(PET-CT)revealed metastasis to the right superior rectus muscle.No intracranial tumor progression was observed.The Cyberknife system(20 Gy/1 Fr)was used for treating the orbital tumor. Increased LYM was observed even after 2 courses of S-1 plus oxaliplatin(SOX)therapy.Therefore, weekly combination therapy of paclitaxel and ramucirumab(wPTX plus Rmab)was administered as second-line therapy.No new distal metastasis has been detected in the 10 months since the orbital metastasis development, and the patient is still alive.

Open surgery versus laparoscopic surgery after stent insertion for obstructive colorectal cancer.

PURPOSE: To compare the outcomes of laparoscopic surgery vs. open surgery after insertion of a colonic stent for obstructive colorectal cancer. METHODS: Between April 2005 and August 2013, 58 patients underwent surgery after the insertion of a colonic stent for obstructive colorectal cancer. We analyzed the outcomes of the patients who underwent laparoscopic surgery vs. those who underwent open surgery. RESULTS: We compared blood loss, operative time, hospital stay, and complications in 26 patients who underwent laparoscopic surgery and 32 patients who underwent open surgery. Blood loss was significantly less in the laparoscopic surgery group, but operative time was significantly shorter in the open surgery group. The length of hospital stay was shorter in the laparoscopic surgery group than in the open surgery group, but the difference was not significant. There was no significant difference in postoperative surgical complications between the groups. CONCLUSION: The patients who underwent laparoscopic resection had less blood loss, although no significant difference was found in postoperative morbidity or mortality. Thus, laparoscopic resection after stent insertion is a feasible and safe option for patients with obstructive colorectal cancer.

Resection of a giant cardiac hemangioma.

We present a case of a 61-year-old female who underwent excision of the mass within left atrial appendage. She underwent cardiac surgery due to cardiac tumor. The tumor was measured 6 cm, and it was completely resected. After surgery, pathological examination diagnosed endocardiac-based cardiac hemangioma. The post operative course was uneventful and the patient discharged on the 18th postoperative day.