Immunotherapeutic allogeneic dendritic cell and autologous tumor cell fusion vaccine alone or combined with radiotherapy in canine oral malignant melanoma is safe and potentially effective.

Introduction: Immunotherapy represents a promising breakthrough in cancer management and is being explored in canine melanomas. Dendritic cells (DCs) play a crucial role in priming T-cell-mediated immune reactions through the antigen-presenting function. Combining immunotherapy and radiation therapy may generate more substantial anti-cancer efficacy through immunomodulation. Objectives: Our research reported a preliminary result of the safety and outcome of a kind of immunotherapy, the allogeneic dendritic cell and autologous tumor cell fusion vaccine, alone or in combination with hypofractionated radiation therapy, in canine oral malignant melanoma. Methods: Two groups of dogs with histopathological diagnoses of oral malignant melanoma were recruited. In group 1 (DCRT), dogs received a combination of DC fusion vaccine and radiotherapy. In group 2 (DC), dogs received DC fusion vaccine alone. DC vaccination was given once every 2 weeks for four doses. Radiotherapy was performed weekly for five fractions. Dogs that received carboplatin were retrospectively collected as a control group (group 3). Results: Five dogs were included in group 1 (two stage II, three stage III), 11 in group 2 (three stage I/II, eight stage III/IV), and eight (two stage I/II, six stage III/IV) in the control group. Both DC and DCRT were well-tolerated, with only mild adverse events reported, including mucositis, gastrointestinal discomfort, and injection site reactions. The median progression-free intervals in groups 1, 2, and 3 were 214 (95% CI, NA, due to insufficient data), 100 (95% CI, 27-237), and 42 days (95% CI, NA-170), respectively, which were not significantly different. The 1-year survival rates were 20, 54.5, and 12.5% in groups 1, 2, and 3. Dogs in the DCRT group exhibited significantly higher TGF-ß signals than the DC group throughout the treatment course, indicating a possible higher degree of immunosuppression. Conclusion: The manuscript demonstrated the safety of dendritic cell/tumor cell fusion vaccine immunotherapy, alone or in combination with radiotherapy. The results support further expansion of this immunotherapy, modification of combination treatment and protocols, and investigation of combining DC vaccine with other treatment modalities. Clinical trial registration: Preclinical Trials, PCTE0000475.

Diagnostic Value of Conventional Polymerase Chain Reaction for Detecting BRAF V595E Mutation in Liquid and Tissue Specimens of Canine Urothelial and Prostate Carcinomas.

Canine urothelial carcinoma (UC) and prostatic carcinoma (PC) often present diagnostic challenges due to their anatomical locations. The BRAF V595E mutation, analogous to the human BRAF V600E mutation, has been identified in UC and PC. Digital PCR of urine is a non-invasive diagnostic method of mutation detection, but the availability of the necessary equipment is limited. This study aimed to develop a conventional PCR to detect the BRAF V595E mutation in urine and prostatic wash specimens from dogs with UC or PC. Specific primers for detecting wild-type and mutant BRAF V595E genes were validated in 34 formalin-fixed paraffin-embedded (FFPE) tissues, 116 urine samples, and 9 prostatic wash specimens. The results showed that the BRAF V595E mutation detection rate for UC and PC in the tissues was 51.6%. The detection rate in liquid specimens from dogs with lower urinary tract or prostate masses was 53.2%. Of the 41 cases with follow-up, 16 were further diagnosed with UC or PC, with 75% of liquid specimens from these dogs showing the BRAF V595E mutation. This conventional PCR method provides a reliable and non-invasive screening tool for UC and PC in dogs, especially in settings without advanced equipment.

The urinary shedding of porcine teschovirus in endemic field situations.

Porcine teschoviruses (PTVs) belong to the genus Teschovirus within the family Picornaviridae. PTVs are universal contaminants in pig herds in endemic and multi-infection statuses. Previous research has demonstrated PTV antigens and nucleic acid in renal glomeruli and tubular epithelia, suggesting the possibility that PTVs might be shed and transmitted via urine. The study aimed to demonstrate, in the context of pathogenesis, the presence of PTVs in the urine of naturally infected pigs. Viral loads of fluid and tissue samples quantified by an established qRT-PCR showed detection rates of 100% by head and in urine, feces, plasma and nasal swabs, and 38% in kidney. As predicted, PTVs were present in urine at 10(4.02 ± 1.45) copies/100 µl volume, equivalent to 17% of that in plasma. No significant differences were observed between healthy and culled pigs or among the 7 sampled herds. The presence of PTVs in urine was further substantiated by molecular serotyping. In particular, PTV-10 was identified in the urine of 3 piglets from 3 separate herds, consistent with the most prevalent serotype found in this study, and in plasma. The urine mixes with feces to form slurry making it easier for PTV to spread and contaminate the environment.

Parity, age at first birth and risk of death from kidney cancer: a population-based cohort study in Taiwan.

BACKGROUND: This study was undertaken to examine whether there is an association between parity and age at first birth and risk of kidney cancer. METHODS: The study cohort consisted of 1 292 462 women who had a first and singleton childbirth between 1 January 1978 and 31 December 1987. We tracked each woman from the time of her first childbirth to 31 December 2009, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of death from kidney cancer associated with parity and age at first birth. RESULTS: There were 95 kidney cancer deaths during 34,980,246 person-years of follow-up. The mortality rate of kidney cancer was 0.27 cases per 100,000 person-years. The adjusted HR was 1.88 [95% confidence interval (CI) 1.10-3.19] for women who gave birth between 24 and 26 years of age and 2.52 (95% CI 1.44-4.40) for women who gave birth after 26 years of age, when compared with women who gave birth when <23 years of age. A trend of increasing risk of kidney cancer was seen with increasing age at first birth. The adjusted HR was 0.88 (95% CI 0.49-1.59) for women who had two children and 0.89 (95% CI 0.47-1.67) for women with three or more births, when compared with women who had given birth to only one child. CONCLUSION: This study is the first to suggest that early age at first birth may confer a protective effect on the risk of kidney cancer.

Fine particulate air pollution and hospital admissions for myocardial infarction in a subtropical city: Taipei, Taiwan.

This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions for MI was estimated using a casecrossover approach, controlling for weather variables, day of the week, seasonality, and longterm time trends. For the single-pollutant model (without adjustment for other pollutants), increased numbers of MI admissions were significantly associated with higher PM2.5 levels both on warm days (>23°C) and on cool days (<23°C). This was accompanied by an interquartile range elevation correlated with a 10% (95% CI = 6-15%) and 5% (95% CI = 1-9%) rise in number of MI admissions, respectively. In the two-pollutant models, PM2.5 remained significant after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for MI.

Comparison between calcitriol and calcitriol plus low-dose cinacalcet for the treatment of moderate to severe secondary hyperparathyroidism in chronic dialysis patients.

AIM: Uremic hyperparathyroidism (UHPT) has been shown to contribute to the development and progression of chronic kidney disease-mineral bone disorder. UHPT is frequently observed in chronic dialysis patients, and patients with UHPT are associated with increased risk of all-cause and cardiovascular mortality. Cinacalcet is a novel agent that increases sensitivity to the calcium-sensing receptor and is approved for control of UHPT. Nevertheless, cinacalcet is costly and information regarding efficacy of low-dose cinacalcet on UHPT is limited. METHODS: We conducted a retrospective study to evaluate treatment with either low-dose calcitriol combined with low-dose cinacalcet (25 mg) (d-cinacalcet) or calcitriol alone (VitD) in dialysis patients with moderate to severe UHPT. A total of 81 dialysis patients were enrolled (40 subjects in d-cinacalcet group and 41 subjects in VitD group). Demographic data including age, gender, duration on dialysis and biochemical data were reviewed and recorded. RESULTS: At the end of the study, the intact parathyroid hormone (iPTH) levels of the d-cinacalcet group declined significantly (from 1166.0 ± 469.3 pg/mL to 679.8 ± 421.6 pg/mL, p < 0.0001), while there was no significant change in the VitD group. Significant decrease of serum calcium (Ca: 9.9 ± 0.6 mg/dL vs. 9.6 ± 0.8 mg/dL, p = 0.002), phosphorus (P: 5.9 ± 1.3 mg/dL vs. 4.9 ± 0.9 mg/dL, p < 0.0001) and calcium phosphate product (Ca × P: 58.7 ± 15.0 mg2/dL2 vs. 46.9 ± 8.9 mg2/dL2, p < 0.0001) were observed in the d-cinacalcet group. In addition, the subjects in the d-cinacalcet group had a greater proportion to achieve Kidney Disease Outcomes Quality Initiative (KDOQI)-recommended biochemical targets than the subjects in the VitD group (Ca: 48% vs. 24%; P: 78% vs. 32%; Ca × P: 85% vs. 37%; iPTH: 15% vs. 0%). CONCLUSIONS: We conclude that combination therapy of low-dose cinacalcet and calcitriol is more effective than calcitriol alone as a treatment for moderate and severe UHPT in chronic dialysis patients. Furthermore, this therapy is associated with improvement in hyperphosphatemia and hypercalcemia.

Biomarkers associated with vascular and valvular calcification in chronic hemodialysis patients.

BACKGROUND: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients. METHODS: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared. RESULTS: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC. CONCLUSIONS: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients.

The risk of upper gastrointestinal bleeding in patients treated with hemodialysis: a population-based cohort study.

BACKGROUND: There are no prior studies that have estimated the risk of upper gastrointestinal bleeding (UGIB) among the dialysis population relative to the general population. The aim of this study was to examine the risk of UGIB among end-stage renal disease (ESRD) patients during a 6-year period following their initiation of hemodialysis (HD) therapy in Taiwan- a country with the highest incidence of ESRD in the world, using general population as an external comparison group. METHODS: Data were obtained from the Taiwan National health Insurance Research Database. In total, 796 patients who were beginning HD between 1999 and 2003 were recruited as the study cohort and 3,184 patients matched for age and sex were included as comparison cohort. Multivariate Cox proportional hazard regression models were used to adjust for confounding and to compare the 6-year UGIB-free survival rate between these two cohorts. RESULTS: The incidence rate of UGIB (42.01 per 1000 person-year) was significantly higher in the HD cohort than in the control cohort (27.39 per 1000 person-years). After adjusting for potential confounders, the adjusted hazard ratios for UGIB during the 6-year follow-up periods for HD patients was 1.27 (95% CI=1.03-1.57) compared to patients in the comparison cohort. CONCLUSIONS: We conclude that HD patients were at an increased risk for UGIB compared with the general population.

Parity, age at first birth, and risk of death from chronic renal failure: a cohort study of parous women in Taiwan.

BACKGROUND: This study was undertaken to examine whether there is an association between parity and age at first birth and risk of death from chronic renal failure (CRF). STUDY DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The study cohort consisted of 1 292 462 women who had a first and singleton childbirth between January 1, 1978 and December 31, 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. PREDICTORS: Parity and age at first birth. OUTCOME: Death of chronic renal failure (CRF). RESULTS: There were 225 CRF deaths during 34 980 246 person-years of follow-up. The mortality rate of CRF was 0.64 cases per 100 000 person-years. Adjusted hazard ratios (HRs) were 1.75 (95% CI= 1.30-2.36) for women who gave birth between 26 and 30 years, 2.52 (95% CI=1.57-4.04) for women who gave birth after 30 years, respectively, when compared with women who gave birth younger than 25 years. Adjusted HRs were 0.47 (95% CI= 0.33-0.66) for women who had two children, and 0.40 (95% CI=0.28-0.58) for women with three or more births, respectively, when compared with women who had given birth to only one child. There was a significant decreasing trend in the HRs of CRF death with increasing parity. CONCLUSIONS: This study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of CRF death.

Death of a son is associated with risk of suicide among parous women in Taiwan: a nested case-control study.

BACKGROUND: The impact of the sex of a deceased child on maternal suicide has not been studied. We examined whether the death of a child, especially a son, increased the risk of suicide among parous Taiwanese women. METHODS: This matched case-control study was done within a cohort of 1 292 462 Taiwanese women who experienced a first and singleton childbirth between 1 January 1978 and 31 December 1987 and were followed up until 31 December 2008. From the cohort, 2701 suicide cases were identified and 2701 controls were randomly selected. Multiple logistic regression was used to estimate the risk of suicide associated with the death of a child. RESULTS: The adjusted odds ratios (ORs) for suicide among mothers whose son had died were 2.60 (95% CI = 1.18-5.73), 2.58 (1.28-5.20), and 4.20 (0.79-22.45) for death of a son aged younger than 1 year, 1 to 17 years, and 18 years or older. The ORs for suicide associated with the death of a daughter were not statistically significant: the respective adjusted ORs were 1.86 (0.82-4.62), 1.38 (0.54-3.49), and 2.48 (0.40-15.51). CONCLUSIONS: The death of a child, especially a son, increased the risk of maternal suicide, which supports the notion that preference for a son is firmly rooted in traditional Chinese culture.

Statin use and the risk of bladder cancer: a population-based case-control study.

OBJECTIVE: The aim of this study was to investigate whether the use of statins is associated with bladder cancer risk. METHODS: The authors conducted a population-based case-control study in Taiwan. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of bladder cancer, for the period between 2004 and 2010. The controls were matched to cases by age, sex and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS: The authors examined 325 bladder cancer cases and 1300 controls. The unadjusted ORs for any statin prescription was 0.94 (95% CI 0.70 - 1.28) and the adjusted OR was 0.88 (95% CI 0.61 - 1.25). Compared with no use of statins, the adjusted ORs were 0.72 (95% CI 0.40 - 1.28) for the group having been prescribed statins with cumulative defined daily dose (DDDs) below 56 DDDs, 0.81 (95% CI 0.46 - 1.43) for the group with cumulative dose between 56 DDDs and 196 DDDs, and 1.11 (95% CI 0.67 - 1.85) for the group with cumulative statin use of 196 DDDs or more. CONCLUSIONS: The present data do not provide evidence to support either beneficial or harmful associations between statin use and bladder cancer risk.

Free p-cresol sulfate is associated with survival and function of vascular access in chronic hemodialysis patients.

BACKGROUND: Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresol sulfate (p-CS) have been implicated as an important factor in uremic syndrome. Recent evidence indicates that both IS and p-CS are predictors of cardiovascular as well as all-cause mortality among chronic dialysis patients. We conducted a study to analyze the relationship between IS and p-CS and vascular access (VA) outcome in chronic hemodialysis (HD) patients. METHODS: A total of 91 chronic stable HD patients were divided into groups according to survival of VA and frequency of VA dysfunction. Demographic and biochemical data were reviewed and recorded. Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, and the total and free forms of IS and p-CS were determined. RESULTS: Patients with a history of frequent VA failure and dysfunction had lower albumin and higher levels of ICAM-1, free IS, free and total p-CS. Diabetes was associated with higher IS and p-CS. Logistic regression revealed that diabetes and free p-CS were independent factors associated with poor outcome of VA. CONCLUSION: Endothelial dysfunction and uremic toxins were associated with survival and function of VA. Diabetes and free p-CS were significantly related to the outcome of VA among chronic HD patients.

Disrupted circadian rhythm in rats with nephrectomy-induced chronic kidney disease.

AIMS: Our study investigated the role of circadian rhythm in the pathogenesis of sleep disturbance in patients with chronic kidney disease (CKD) based on an animal model. MAIN METHODS: Sixteen Sprague-Dawley (SD) rats (eight from 5/6 nephrectomized CKD group and eight from control group) were used for electroencephalography (EEG) and electromyography (EMG) recording. Eight rats (four from CKD and four from control group) were sacrificed at six Zeitgeber time (ZT) points and determined the mRNA expression of clock genes, rPer1, rPer2 and rBMAL1b in the hypothalamus. KEY FINDINGS: Our results demonstrated that both slow wave sleep (SWS) and rapid eye movement (REM) sleep were significantly increased in the ZT22-24 Zeitgeber time point of the dark period in the CKD rats when compared with those sleep architectures obtained from the control rats. The CKD-induced sleep disruptions were associated with significant upregulations of rPer1 (in ZT2, ZT6 and ZT14) and rPer2 mRNA expression (in ZT2 and ZT14) in the hypothalamus. SIGNIFICANCE: Our study elucidated that the increases of SWS and REM sleep during ZT22-24 of the dark period in the CKD rats might be due to the enhancement of rPer1 and rPer2 clock genes in the hypothalamus, suggesting that disrupted circadian rhythm plays a role in the pathogenesis of sleep disturbance in patients with CKD.

Relationship between Kt/V urea-based dialysis adequacy and nutritional status and their effect on the components of the quality of life in incident peritoneal dialysis patients.

BACKGROUND: It is well known that the quality of life of patients with chronic kidney disease can be improved by dialysis. While previous studies have used retrospective designs and adhered to a standard target prescribed by clinical guidelines, our study prospectively investigates the association between the adequacy of peritoneal dialysis (PD) and measures of nutritional status on quality-of-life domains in a cohort of incident PD patients. METHODS: It was a prospective 6-month observational study. Eighty incident PD participants who were treated in a hospital-based PD center were enrolled. The period of enrollment was January 2009-June 2010; follow-up continued until December 2010. PD adequacy indices, including Kt/V urea, weekly Ccr (WCcr), measures of nutritional status (albumin, BMI), and nPCR were measured at 1 month and 6 months after PD initiation. SF-36 health survey questionnaires were used to measure the quality of life. The outcomes were used to measure the changes in the domains of the SF-36 after 6 months of PD therapy. RESULTS: Seventy-seven incident patients who underwent PD for 6 months were included in the study. The mean age was 47.3 years, and the male-to-female ratio was 38:39. A peritoneal Kt/V urea value of 1.2, which was also the baseline cutoff value, was found to have the highest influence on SF-36 domains. Patients with baseline peritoneal Kt/V urea value of <1.2 showed improvement in the physical functioning and role limitation of physical functioning components after 6 months of PD. In contrast, patients with baseline peritoneal Kt/V urea values of ≥1.2 showed remarkable improvement in the general health, physical functioning, role limitation caused by physical problems, and bodily pain components. However, the trend of improvement decreased in patients with baseline nPCR of <1.2. Baseline renal WCcr did not influence the improvement in the SF-36 domains. LIMITATIONS: A small cohort and a short observation period. CONCLUSIONS: The baseline level of peritoneal Kt/V urea affected the components of the quality of life after PD initiation. In contrast, a lower baseline nPCR level was associated with deterioration in the quality of life after PD therapy.

Higher parity and earlier age at first birth are associated with lower risk of death from colon cancer.

This study was undertaken to examine whether there is an association between parity and age at first birth and risk of colon cancer. The study cohort consisted of 1,292,462 women who had a first and singleton childbirth between 1978 and 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. We used the Cox proportional hazards model with time-dependent covariates to estimate the hazard ratios (HR) of death from colon cancer associated with parity and age at first birth. We limited eligible colon cancer deaths to those who were 45 years old or more to exclude possible heredity colon cancer cases, which usually occur at an early age. There were 670 colon cancer deaths during 34,980,246 person-years of follow-up. The colon cancer death rate was 1.96 cases per 100,000 person-years. The adjusted HR was 2.76 (95% CI = 1.60-4.75) for women who gave birth between 20 and 24 years and 7.35 (95% CI = 4.28-12.62) for women who gave birth after 24 years of age when compared with women who gave birth at younger than 20 years. A rising risk of colon cancer was seen with increasing age at first birth. The adjusted HR were 0.81 (95% CI = 0.65-1.02) among women with two live births, 0.93 (95% CI = 0.74-1.18) among women with three live births and 0.72 (95% CI = 0.51-1.00) for women with four or more births when compared with women who had given birth to only one child. The present study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of colon cancer.

Statin use and the risk of kidney cancer: a population-based case-control study.

OBJECTIVE: To investigate whether the use of statins was associated with kidney cancer risk. METHODS: We conducted a population-based case-control study in Taiwan. Cases consisted of all patients who were aged 50 years and older, and had a first-time diagnosis of kidney cancer for the period between 2005 and 2009. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS: We examined 177 kidney cancer cases and 708 controls. The adjusted OR for any statin prescription was 1.08 (95% CI = 0.70 - 1.67). Compared with no use of statins, the adjusted ORs were 0.91 (95% CI = 0.50 - 1.63) for the group having been prescribed statins with cumulative defined daily dose (DDDs) below 105 and 1.28 (95% CI = 0.73 - 2.23) for the group with cumulative statin use of 105 DDDs or more. CONCLUSIONS: The present data do not provide evidence to support either beneficial or harmful associations between statin use and kidney cancer risk. However, there is a trend of increased kidney cancer risk with higher cumulative DDDs, and consequently that it is prudent to continue monitoring cancer incidence among long-standing statin users.

Risk of herpes zoster in patients treated with long-term hemodialysis: a matched cohort study.

BACKGROUND: The risk of herpes zoster in the dialysis population relative to the general population is not known. The aim of this study was to perform a population-based cohort study to investigate the risk of herpes zoster after the initiation of hemodialysis therapy in patients with end-stage renal disease (ESRD) in Taiwan, a country with the highest incidence of ESRD in the world. STUDY DESIGN: Matched cohort study. SETTING & PARTICIPANTS: Data were obtained from the Taiwan National Health Insurance Research Database. 843 patients who were beginning hemodialysis therapy in 1999-2003 were included as the study cohort and 3,372 patients without ESRD matched for age and sex were included as a comparison cohort. A multivariate frailty Cox proportional hazard regression model was used to adjust for confounding and compare the 6-year herpes zoster-free survival rate between these 2 cohorts. PREDICTORS: Hemodialysis. OUTCOMES: Herpes zoster. RESULTS: Mean years of follow-up were 4.73 and 5.49 for the hemodialysis and comparison cohorts, respectively. 868 patients developed herpes zoster throughout the study period, 294 from the hemodialysis cohort and 574 from the comparison cohort. The incidence rate of herpes zoster (73.34 events/1,000 person-year) was significantly higher in the hemodialysis cohort than in the control cohort (31.03 events/1,000 person-years). After adjusting for potential confounders, the adjusted HR of herpes zoster was 1.98 (95% CI, 1.72-2.27). LIMITATIONS: We expect that some patients with mild zoster chose not to seek medical help. CONCLUSIONS: We conclude that patients treated with long-term hemodialysis are at an increased risk of herpes zoster compared with the general population.

Haemodialysis and the risk of stroke: A population-based cohort study in Taiwan, a country of high incidence of end-stage renal disease.

AIMS: Data regarding the occurrence of stroke in dialysis patients are limited and epidemiologic studies to date are controversial with respect to the stroke subtype among dialysis patients. The aim of this study was to perform a population-based study with a retrospective cohort design to investigate the risk of stroke after the initiation of haemodialysis (HD) among end-stage renal disease (ESRD) patients in Taiwan - a country with the highest incidence of ESRD in the world. METHODS: Data were retrospectively obtained from the Taiwan National Health Insurance Research Database. In total, 644 patients who were beginning HD between 1999 and 2003 were recruited as the study cohort and 3220 patients matched for age and sex were included as the comparison cohort. Multivariate Cox proportional hazard regression models were used to adjust for confounding and to compare the 5 year stroke-free survival rate between these two cohorts. RESULTS: The incidence rate of stroke (41.76 per 1000 person-years) was significantly higher in the HD cohort than in the control cohort (24.29 per 1000 person-years). After adjusting for potential confounders, the adjusted hazard ratios of ischaemic stroke and haemorrhagic stroke were 2.16 (95% confidence interval = 1.57-2.97) and 3.78 (95% confidence interval = 1.90-7.55), respectively. CONCLUSION: We conclude that HD patients were at an increased risk for both ischaemic and haemorrhagic stroke compared with the general population.

Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells.

AIMS: Endothelial dysfunction is a common manifestation of chronic kidney disease (CKD). The protein-bound uremic toxins have emerged as important factors associated with cardiovascular disease and the outcome of CKD. The effect of indoxyl sulfate (IS) on endothelial cells remains unclear. MAIN METHODS: Human umbilical endothelial cells (HUVEC) were incubated using IS at two concentrations: 100 µM and 1000 µM over two periods of time: 16 and 48 h. HUVEC were also pre-treated with simvastatin to examine its effect. RT-PCR was used to assess changes in the gene expression of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), Monocyte chemotactic protein-1 (MCP-1), E-selectin, and angiotensin receptor type 1 (AT1R). Protein abundance of the investigated molecules was assessed by immunoblotting. KEY FINDINGS: Treatment with 100 µM IS for 16 h induced a 2-fold increase in the expression of ICAM-1, VCAM-1, and MCP-1. At a concentration of 1000 µM, there was a 2-3-fold increase. An extended treatment period at low concentrations was associated with a 2-3 fold increase and the increase of ICAM-1 and VCAM-1 was more prominent under high concentration. Results of immunoblotting confirmed an increase in the abundance of ICAM-1, VCAM-1 and MCP-1. No significant change was noted in E-selectin and AT1R according to concentration or treatment duration. Pre-treatment with simvastatin did not alter IS-induced changes. SIGNIFICANCE: IS increased the expression of adhesion molecules of endothelial cells exhibiting a concentration and duration dependent pattern. Simvastatin did not demonstrate any effect on IS-associated endothelial activation.

Proinflammatory cytokines, hepatocyte growth factor and adipokines in peritoneal dialysis patients.

Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) but not with IL-10 and IL-18. IL-6 correlated with TNF-alpha, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-alpha, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients.