Comparison between the 0- and 30-s balloon dilation time in percutaneous transluminal angioplasty for restenosed arteriovenous fistula among hemodialysis patients: a multicenter, prospective, randomized trial (CARP study).

BACKGROUND: This study aims to compare patency rates of the 0- and 30-s (sec) balloon dilation time in hemodialysis (HD) patients with restenosis after percutaneous transluminal angioplasty (PTA). METHODS: The patients who underwent PTA within 6 months for failed arteriovenous fistula at the forearm were randomly assigned the 0-s or 30-s dilation time group. Effect of dilation time on the 3- and 6-month patency rates after PTA was examined. RESULTS: Fifty patients were enrolled in this study. The 3-month patency rate in the 30-s dilation group was better than that in the 0-s dilation group (P = 0.0050), while the 6-month patency rates did not show a significant difference between the two groups (P = 0.28). Cox's proportional hazard model revealed that 30-s of inflation time (hazard ratio 0.027; P = 0.0072), diameter of the proximal (hazard ratio 0.32; P = 0.031), and dilation pressure (hazard ratio 0.63; P = 0.014) were associated with better 3-month patency. Dilation pressure between previous and present PTA did not differ in the 0-s (P = 0.15) and 30-s dilation groups (P = 0.16). The 6-month patency rate of the present PTA in the 30-s dilation group was higher than that of the previous PTA (P = 0.015). The visual analog scale did not differ between the two groups (P = 0.51). CONCLUSION: The presenting data suggest that 30-s dilation potentially results in a better 3-month patency rate than 0-s dilation in HD patients with restenosis after PTA.

Prognostic Relevance of Pretreatment Peripheral Neutrophil Count and Neutrophil-to-lymphocyte Ratio in Primary Cutaneous Angiosarcoma.

Systemic inflammatory response markers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and monocyte-to-lymphocyte ratio, are useful prognostic factors for various malignant tumours. The aim of this study was to investigate the clinical relevance of these markers in primary cutaneous angiosarcoma. Twenty-six patients were retrospectively divided into 2 groups according to pretreatment peri-pheral blood cell counts or systemic inflammatory response marker levels; overall survival and progression-free survival were compared. Univariate analysis found that high neutrophil count (> 3.1×109/l), high neutrophil-to-lymphocyte ratio (> 2.4), high platelet-to-lymphocyte ratio (> 175) and low lymphocyte count (≤ 1.3×109/l) were related to shorter overall survival, while high neutrophil and low lymphocyte groups had shorter progression-free survival. In multivariate analysis, high neutrophil count and high neutrophil-to- lymphocyte ratio (hazard ratio 7.44 and 5.04, 95% confidence interval 1.48-37.2 and 1.26-20.1, respectiv-ely) were identified as independent prognostic factors for poor overall survival. These results indicate that systemic inflammatory response markers serve as prognostic predictors in primary cutaneous angiosarcoma, as well as in other types of soft-tissue sarcoma.

Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan.

Recent evidence on maintenance administration of epoetin beta pegol, a continuous erythropoiesis receptor activator (CERA), in dialysis patients shows the clinical benefit of bi-weekly administration (Q2W) in improving hematopoiesis and iron use efficiency. We undertook a single-center observational study of 33 Japanese maintenance dialysis patients, whose anemia had been kept stable through weekly administration (Q1W) of darbepoetin (DA), to evaluate the effectiveness of CERA Q2W switched from DA in maintaining hemoglobin (Hb) levels over a 12-month period. The target Hb level was 10.0-12.0 g/dL. Throughout the 12-month period, the mean Hb was stably maintained at 10.5-10.8 g/dL, 69.7-87.9% of the patients achieving the target Hb level. The mean CERA dose was within the range of 62.9-78.8 µg/2 weeks. The average CERA dose adjustment frequency after switching was low at 0.42-0.67 times/3 months. In both subgroups stratified by the DA dose prior to the switch, Hb levels were kept stable during CERA administration; however, in the low-dose group (10-20 µg/week of DA), the CERA and iron doses decreased over time, whereas in the high-dose group (30-60 µg/week of DA) they remained unchanged. CERA Q2W achieved long-term successful anemia management in Japanese maintenance dialysis patients after switching from DA Q1W. CERA dose was adjusted based on an overall consideration of past changes in Hb levels, erythropoiesis-stimulating agent and iron doses. Subgroup analysis showed the CERA dose in the low-dose group decreased continuously, due possibly to a long-term improvement in iron use efficiency.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Efficacy of add-on therapy of aliskiren to an angiotensin II receptor blocker on renal outcomes in advanced-stage chronic kidney disease: a prospective, randomized, open-label study.

BACKGROUND: Combination therapy of aliskiren and an angiotensin II receptor blocker (ARB) has been reported to be effective for reducing the level of proteinuria. However, it remains unclear whether this combination therapy contributes to suppression of kidney disease progression. The aim of this study was to investigate the effect of aliskiren on hard renal endpoints, when added to an ARB, in patients with advanced chronic kidney disease (CKD). METHODS: The study design was a prospective, randomized open-label design. 83 CKD patients (52 men and 31 women) were enrolled and assigned randomly to an aliskiren add-on group (n = 42) or control group (n = 41). Entry criteria included elevated serum creatinine ≥ 1.5 mg/dl, urine protein excretion (≥ 1+ on urine dipstick test), and hypertension. All participants were treated with an ARB. The follow-up period was 12 months. 12 participants were withdrawn during the study period and the study was terminated in January 2012 as a consequence of the results of the interim analysis of the ALTITUDE study. RESULTS: Nine patients in the aliskiren group and seven patients in the control group started dialysis. Doubling of the serum creatinine level occurred in one patient in the control group. A Cox proportional hazards test showed that dual blockade of the renin-angiotensin-aldosterone system with aliskiren and ARB was not associated with improvement in hard renal endpoints. CONCLUSION: We conclude that aliskiren add-on therapy to an ARB may not give any benefit and, therefore, should not be recommended in CKD patients.

A new metric for long-range transport potential of chemicals.

We propose a new metric for long-range transport potential (LRTP), GIF, based on source-receptor analyses and evaluate the LRTP and persistence of a wide variety of chlorinated and brominated organic compounds using GIF and overall persistence (POV), respectively. We calculated GIF and POV using our global 3D dynamic multimedia model (FATE). Physicochemical properties were obtained from quantitative structure-property relationship (QSPR) models. The FATE-QSPR combined model enabled us to systematically investigate the LRTP and persistence of a wide variety of chemical substances. On average, the estimated GIF and POV for chlorinated compounds were larger than those for their brominated counterparts, with the largest and smallest values found for polychlorinated biphenyls and polybrominated dibenzodioxins, respectively. We also compared GIF with four differently defined LRTP metrics and two LRTP metrics obtained from a simple model. The results of our analyses indicate that the LRTP ranks can differ considerably among LRTP metrics, the differences being dependent on the governing environmental processes, relevant physicochemical properties, and multimedia model.

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Committee report: Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy.

Background: Patients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis. Methods: A questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021. Results: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities. Conclusions: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy.

Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis.

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.

Vitamin K2 alters bone metabolism markers in hemodialysis patients with a low serum parathyroid hormone level.

BACKGROUND: A low level of intact parathyroid hormone (PTH) is an indicator of adynamic bone disease in hemodialysis patients, and is associated with a significant increase of all-cause mortality. Thus, effective treatment for adynamic bone disease is required. We previously investigated the effect of vitamin K2 on adynamic bone disease. In this study, we assessed the efficacy of oral vitamin K2 in a controlled trial. METHODS: Forty hemodialysis patients with low intact PTH levels (<100 pg/ml) were randomly divided into two groups, which were a vitamin K2 group receiving oral menatetrenone (45 mg/day) for 1 year and a control group without vitamin K2. Venous blood samples were collected at baseline and during the study for measurement of bone metabolism parameters. RESULTS: Thirty-three patients completed follow-up. There was a significant increase of the serum intact osteocalcin level after 1 month of vitamin K2 administration. Serum levels of intact PTH, bone alkaline phosphatase, and cross-linked N-terminal telopeptide of type I collagen increased significantly after 12 months in the vitamin K2 group. The serum osteoprotegerin level was decreased after 12 months in the vitamin K2 group, but the change was not significant. CONCLUSION: Vitamin K2 therapy improves bone remodeling in hemodialysis patients with a low intact PTH level.

Different risk factors are associated with vascular access patency after construction and percutaneous transluminal angioplasty in patients starting hemodialysis.

BACKGROUND: The objective of this multicenter, prospective observational study was to determine the factors related to patency rates after construction of vascular access (VA) and the first percutaneous transluminal angioplasty (PTA). METHODS: The 24-month primary and secondary patency rates after construction of a radiocephalic arteriovenous fistula (RC-AVF) and arteriovenous graft (AVG) were evaluated using the Kaplan-Meier method and log-rank test. The 12-month post-PTA patency rate was also investigated. A Cox proportional hazard model was used to identify clinical parameters associated with the primary patency rate and the post-PTA patency rate. RESULTS: A total of 611 patients were enrolled in the study. The primary patency rate after VA construction was lower in hemodialysis (HD) patients with an AVG than in those with an AVF. Aging (hazard ratio [HR], 1.02 per 1 year; p < 0.001), female sex (HR, 1.41; p = 0.03), diabetes mellitus (HR, 1.37; p = 0.03), low serum albumin (HR, 0.76 per 1-g/dL decrease; p = 0.02), and use of an erythropoietin-stimulating agent (HR, 1.62; p = 0.02) were risk factors for VA problems. The post-PTA patency rate was associated with aging (HR, 1.02; p < 0.001), diabetes mellitus (HR, 1.49; p = 0.02), polycystic kidney disease (HR, 2.14; p = 0.01), temporary catheter use for initiation of HD (HR, 1.60; p = 0.02), and period from VA construction to use (HR, 0.99; p = 0.04). CONCLUSION: Although a poor patency rate is commonly associated with advanced age and diabetes, different risk factors affect patency between VA construction and the first PTA.

Classification of IBV S1 genotypes by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and relationship between serotypes and genotypes of strains isolated between 1998 and 2008 in Japan.

In this study, we attempted to establish a simple detection method for classification of IBV S1 genotypes by direct reverse transcriptase-polymerase chain reaction (RT-PCR). Then, to evaluate the usefulness of the S1 genotype-specific RT-PCR, we examined the relationship between S1 genotypes and serotypes of IBV in Japan. Sequencing of the S1 genes of IBV and phylogenetic tree analysis were conducted. On the basis of the sequencing data of the S1 genotype samples, we determined primer sets specific for each genotype. Five vaccine strains in Japan as reference strains and 46 field isolates were classified into different genetic clusters by phylogenetic tree analysis (JP-1, JP-II, JP-III, Mass and 4/91) and were matched to the results of S1 genotype-specific RT-PCR. A cross virus-neutralizing test showed that the five vaccine strains in Japan exhibited different serotypes from each other. The concordance rate of the 46 field isolates between the S1 genotypes and serotypes was 65.2%. The present study indicates that genotype-specific RT-PCR could be a convenient and useful tool for determining IBV serotypes and could contribute to the control of IBV outbreaks in Japan.

[The role of PPARgamma agonists in kidney diseases].

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor that has a central role in the regulation of insulin sensitivity and adipocyte differentiation. Expression of PPARgamma has been reported in the kidney, including medullary collecting ducts, glomeruli and tubular cells. Thiazolidinediones (TZDs) are synthetic PPARgamma agonists and are used widely in patients with type 2 diabetes. It has been gradually discovered that TZDs have various other actions, such as vascular protective, anti-inflammatory, anti-fibrotic and anti-proliferative actions, over and above their effects on glucose and lipid metabolism. In this review, we will focus on current knowledge and insights on the role of PPARgamma agonists in kidney diseases, especially in diabetic nephropathy, non-diabetic kidney diseases and dialysis therapy.

PPAR-gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-beta.

Thiazolidinediones (TZDs), synthetic peroxisome proliferator-activated receptor (PPAR)-gamma ligands, have a central role in insulin sensitization and adipogenesis. It has been reported that TZDs exert protective effects in both diabetic and nondiabetic models of renal disease, although the exact mechanism is not well understood. In particular, only a few studies have reported the renoprotective effects of TZDs in nondiabetic models of tubulointerstitial fibrosis and inflammation. Therefore, we investigated the anti-fibrotic and anti-inflammatory effects of the TZD troglitazone in the mouse model of unilateral ureteral obstruction (UUO). C57BL/6J mice underwent UUO and were studied after 3 and 7 days. Animals were divided into three groups and received control vehicle, troglitazone (150 mg/kg per day) or troglitazone (300 mg/kg per day) by gavage. Kidneys were harvested for morphological, mRNA and protein analysis. Reverse-transcriptase-PCR was used to assess the expression of transforming growth factor-beta1 (TGF-beta1) and the TGF-beta1 type I receptor (TGF beta R-I). Protein expression was assessed by western blotting (TGF beta R-I) and immunostaining (TGF beta R-I, alpha-smooth muscle actin (alpha-SMA), type I collagen (collagen I), F4/80, and proliferating cell nuclear antigen (PCNA)). The expression of alpha-SMA, collagen I, and F4/80 was decreased in mice treated with troglitazone compared with the control group. The numbers of PCNA-positive interstitial cells were decreased in mice treated with troglitazone. TGF-beta1 mRNA and TGF beta R-I mRNA and protein expression were decreased in the group treated with troglitazone compared with the control group. The beneficial effects of troglitazone treatment were also dose dependent. PPAR-gamma agonist significantly reduced TGF-beta and attenuated renal interstitial fibrosis and inflammation in the model of UUO.

Mizoribine suppresses the progression of experimental peritoneal fibrosis in a rat model.

BACKGROUND/AIMS: Peritoneal fibrosis is a serious complication of peritoneal dialysis (PD). It has been reported that administration of mizoribine, an effective immunosuppressant, ameliorated renal fibrosis in a rat model of unilateral ureteral obstruction. We therefore examined the effects of mizoribine in an experimental model of peritoneal fibrosis. METHODS: 24 rats were given a daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved in saline. The rats were divided into three groups (n = 8 per group) that received either vehicle or mizoribine at a dose of 2 or 8 mg/kg once a day. 28 days after the start of the treatments the rats were sacrificed and peritoneal tissue samples collected. Macrophage infiltration (ED1), myofibroblast accumulation (alpha-smooth muscle actin (SMA)) and expression of type III collagen, transforming growth factor (TGF)-beta and monocyte chemotactic protein-1 (MCP-1) were examined by immunohistochemistry. RESULTS: Mizoribine significantly suppressed submesothelial zone thickening and reduced macrophage infiltration. Mizoribine also reduced collagen III(+) area and decreased the number of alpha-SMA(+), TGF-beta(+) and MCP-1(+) cells. The magnitude of the changes observed was dose-dependent. CONCLUSION: The administration of mizoribine prevented the progression of peritoneal fibrosis in this rat model. Mizoribine may represent a novel therapy for peritoneal sclerosis in patients undergoing long-term PD.

Application of aluminum hydroxide for an in ovo live Newcastle disease vaccine.

Newcastle disease (ND) is a major threat to poultry, but the outbreak of the disease is well controlled by the vaccination. Recently, in ovo administration technology has been realized as a safe, efficacious, and convenient method for chicken vaccination. However, no in ovo administration has been applied for ND or other live vaccines that are highly pathogenic against chicken embryos. We found that an attenuated Newcastle disease virus (NDV) was applicable for an in ovo vaccination by adsorbing the virus to aluminum hydroxide (AH). Pathogenicity to chicken embryos of the AH-adsorbed NDV could be decreased compared with the administration of the virus alone. Namely, in ovo administration of the AH-adsorbed attenuated NDV resulted in improved hatchability and survival rate and better antibody responses of protection-level immunity compared with the administration of NDV alone. However, further improvements in hatchability and survival rate are necessary for practical application. From these results, in ovo vaccination with the AH-adsorbed attenuated NDV was revealed to be safe and immunogenic to chicken embryos. The use of AH-adsorbed attenuated live viruses might be applicable for in ovo vaccinations against not only ND but also other avian infectious diseases.

Up-regulated thromboxane production in the rat liver with biliary obstruction does not contribute to promote hepatic injury.

This study sought to determine whether in vivo inhibition of thromboxane A2 (TXA2) action contribute to attenuate hepatic damage after bile duct ligation (BDL). Male Wistar rats were assigned to sham operation or BDL. At the time of operation, infusion pump with saline, ozagrel natrium (TXA2 synthase inhibitor), or SQ29548 (TXA2 receptor antagonists) was implanted in the abdominal cavity. Plasma alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, and total bilirubin levels were measured at 4 days after the operation. The levels of plasma TXB2, a stable metabolite of TXA2, were significantly increased after BDL. Gene expression of TXA2 synthase was also significantly upregulated in the liver. Nonetheless, either an inhibition of TXA2 synthesis by ozagrel natrium or a blockade of TXA2 receptor by SQ29548 has no effect in every measured parameter related to hepatic function. These results indicated that despite a highly increased production in the liver, TXA2 is not directly related to the hepatic injury in BDL rats.

Comparing the 12-month patency of low- versus high-pressure dilation in failing arteriovenous fistulae: A prospective multicenter trial (YOROI study).

PURPOSE: This study was performed to investigate the effect of the balloon dilation pressure on the 12-month patency rate in patients with failed arteriovenous fistulas undergoing hemodialysis. MATERIALS AND METHODS: In this multicenter, prospective, randomized trial, the 4-mm-diameter YOROI balloon was used for dilation of stenotic lesions. The balloons were inflated to a pressure of 8 atm (low-pressure group) or 30 atm to achieve complete expansion (high-pressure group). The 12-month patency rate after balloon angioplasty was analyzed by the Kaplan-Meier method and log-rank test and/or a Cox proportional hazard model. We also investigated the dilation pressure required to achieve complete expansion in the high-pressure group. RESULTS: In total, 71 patients were enrolled and allocated to either the low-pressure group (n = 34) or the high-pressure group (n = 37). The 12-month patency rates showed no significant difference between the low- and high-pressure groups (47% and 49%, respectively; p = 0.87). In the low-pressure group, the patency rate was not different between patients with complete dilation and residual stenosis (44% and 50%, respectively; p = 0.87). The Cox proportional hazard model revealed that the 12-month patency rate was associated with the stenosis diameter (hazard ratio 0.36; p = 0.001) and the presence of diabetes (hazard ratio 0.33; p = 0.018). Finally, the pressure required to achieve complete dilation was ≤20 atm in 76% of patients and ≤30 atm in 97% of patients. One patient required a dilation pressure of >30 atm. CONCLUSION: The patency rate does not differ between low-pressure dilation and high-pressure dilation.