Dyslipidemia and coronary artery calcium: From association to development of a risk-prediction nomogram.

BACKGROUND AND AIMS: The associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC). METHODS AND RESULTS: This study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis. Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90-1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83-1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06-1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose. CONCLUSIONS: Hypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC.

Galectin-9 Is Critical for Mucosal Adaptive Immunity through the T Helper 17-IgA Axis.

Impairment of the intestinal mucosal immunity significantly increases the risk of acute and chronic diseases. IgA plays a major role in humoral mucosal immunity to provide protection against pathogens and toxins in the gut. Here, we investigated the role of endogenous galectin-9, a tandem repeat-type ß-galactoside-binding protein, in intestinal mucosal immunity. By mucosal immunization of Lgals9-/- and littermate control mice, it was found that lack of galectin-9 impaired mucosal antigen-specific IgA response in the gut. Moreover, Lgals9-/- mice were more susceptible to developing watery diarrhea and more prone to death in response to high-dose cholera toxin. The results indicate the importance of galectin-9 in modulating intestinal adaptive immunity. Furthermore, bone marrow chimera mice were established, and galectin-9 in hematopoietic cells was found to be critical for adaptive IgA response. In addition, immunized Lgals9-/- mice exhibited lower expression of Il17 and fewer T helper 17 (Th17) cells in the lamina propria, implying that the Th17-IgA axis is involved in this mechanism. Taken together, these findings suggest that galectin-9 plays a role in mucosal adaptive immunity through the Th17-IgA axis. By manipulating the expression or activity of galectin-9, intestinal mucosal immune response can be altered and may benefit the development of mucosal vaccination.

First-year estimated glomerular filtration rate variability after pre-end-stage renal disease program enrollment and adverse outcomes of chronic kidney disease.

BACKGROUND: Scarce evidence associates the first-year estimated glomerular filtration rate (eGFR) variability and longitudinal change scales concomitantly to the risk of developing end-stage renal disease (ESRD), acute coronary syndrome (ACS) and death following pre-ESRD program enrollment in chronic kidney disease (CKD). METHODS: We conducted a prospective cohort study of 5092 CKD patients receiving multidisciplinary care between 2003 and 2015 with careful ascertainment of ESRD, ACS and death during the follow-up. First-year eGFR variability and longitudinal change scales that were based on all first-year eGFR measurements included coefficient of variation of eGFR (eGFR-CV), percent change (eGFR-PC), absolute difference (eGFR-AD), slope (eGFR-slope) and area under the curve (AUC). RESULTS: A total of 786 incident ESRD, 292 ACS and 410 death events occurred during the follow-up. In the multiple Cox regression, the fully adjusted hazard ratios (HRs) of progression to ESRD for each unit change in eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope, eGFR-AUC were 1.03 [95% confidence interval (CI) 1.02-1.04], 1.04 (1.03-1.04), 1.16 (1.14-1.18), 1.16 (1.14-1.17) and 1.04 (1.03-1.04), respectively. The adjusted HRs for incident ESRD comparing the extreme with the reference quartiles of eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope and eGFR-AUC were 2.67 (95% CI 2.11-3.38), 8.34 (6.33-10.98), 19.08 (11.89-30.62), 13.08 (8.32-20.55) and 6.35 (4.96-8.13), respectively. Similar direction of the effects on the risk of developing ACS and mortality was observed. In the 2 × 2 risk matrices, patients with the highest quartile of eGFR-CV and concomitantly with the most severely declining quartiles of any other longitudinal eGFR change scale had the highest risk of all outcomes. CONCLUSIONS: The dynamics of eGFR changes, both overall variability and longitudinal changes, over the first year following pre-ESRD program enrollment are crucial prognostic factors for the risk of progression to ESRD, ACS and deaths among patients with CKD. A risk matrix combining the first-year eGFR variability and longitudinal change scales following pre-ESRD enrollment is a novel approach for risk characterization in CKD care. Randomized trials in CKD may be required to ascertain comparable baseline eGFR dynamics.

Prolonged QT interval is linked to all-cause and cardiac mortality in chronic peritoneal dialysis patients.

AIM: Prolonged QT interval is related to changes of electrolytes in haemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients. METHODS: The QT intervals were measured in 2003 and all patients were followed to December 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis. RESULTS: Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 (95% confidence interval (CI): 1.06-2.39, P = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, P = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and < 450 ms) was significantly associated with a worse overall survival (P = 0.03, log-rank test) and cardiac mortality free survival (P = 0.05, log-rank test). CONCLUSIONS: Prolonged QT interval was associated with all-cause and cardiac mortality in patients on peritoneal dialysis. The association is independent of patient's age and diabetes.

Increased risk of hydrocephalus in long-term dialysis patients.

BACKGROUND: The risk of hydrocephalus in end-stage renal disease (ESRD) patients on dialysis has not been studied in depth. METHODS: Using Taiwan National Health Insurance claims data, we identified 29 684 incident ESRD patients from 2000 to 2010, including 10 030 peritoneal dialysis (PD) patients and 19 654 hemodialysis (HD) patients. The control cohort consisted of 118 736 people randomly selected from those without kidney disease, frequency matched with ESRD patients by age, sex and index year. We also established propensity score-matched cohorts with 10 014 PD and 10 014 HD patients. The incidence rates and hazard ratios (HRs) of hydrocephalus were calculated until the end of 2011. RESULTS: Incidence rates of hydrocephalus were greater in HD and PD patients than in controls (8.44 and 11.0 versus 4.11 per 10 000 person-years, respectively), with an adjusted HR of 1.86 [95% confidence interval (CI) 1.43-2.41] for all ESRD patients compared with controls. A higher proportion of hydrocephalus patients underwent surgical bypass to relieve hydrocephalus in ESRD patients than controls, 40.7% (46/113) versus 24.5% (67/273), with an adjusted odds ratio of 2.11 (95% CI 1.33-3.36). Compared with controls, the adjusted HRs of communicating hydrocephalus for HD and PD patients were 1.77 (95% CI 1.22-2.55) and 2.51 (95% CI 1.61-3.89), respectively. The propensity score-matched analysis showed an HR of 0.72 (95% CI 0.42-1.23) for hydrocephalus in HD patients compared with PD patients. CONCLUSIONS: Patients with ESRD are at an increased risk of hydrocephalus. The risk difference between HD and PD patients is not significant.

Icodextrin decreases technique failure and improves patient survival in peritoneal dialysis patients.

AIM: It remains unclear whether long-term daily icodextrin use can decrease technique failure and improve survival in peritoneal dialysis (PD) patients. The aim of the present study was to investigate whether icodextrin use, once daily, can decrease technique failure and prolong patient survival in incident PD patients. METHODS: Incident PD patients who survived more than 90 days were recruited from the China Medical University Hospital, Taiwan, between 1 January 2007 and 31 December 2011. All patients were followed until transfer to haemodialysis (HD), renal transplantation, transfer to another centre, death, or 31 December 2011. RESULTS: A total of 306 incident PD patients (89 icodextrin users, 217 icodextrin non-users) were recruited during the study period. Icodextrin users were more likely to have hypertension, diabetes and high or high-average peritoneal transport compared with non-users. During the follow-up period, 43 patients were transferred to HD: seven (7.87%) of the icodextrin group, and 36 (16.59%) of the non-icodextrin group. Thirty-two patients died during the follow-up period: five (5.62%) of the icodextrin group, and 27 (12.44%) of the non-icodextrin group. Icodextrin use was significantly associated with a better prognosis, in terms of technique failure (adjusted HR = 0.32; 95% CI = 0.14-0.72). With regard to patient survival, icodextrin use (adjusted HR = 0.33; 95% CI = 0.12-0.87) was associated with a significantly lower risk of death. CONCLUSION: The use of icodextrin once daily may decrease technique failure and improve survival in incident PD patients.

Patients with diabetes as the primary kidney disease have a worse survival than patients with comorbid diabetes in chronic haemodialysis patients.

AIM: Diabetes is the leading cause of chronic kidney disease (CKD) that requires dialysis. It is not clear if survival of patients with diabetes as primary kidney disease (DKD) is different from the survival of patients with diabetes as comorbidity (DCM). We investigated the survival of patients with DKD and patients with DCM in patients on maintenance haemodialysis (HD) using propensity score matching approach. METHODS: All patients on maintenance HD in Taiwan Renal Registry Database from 1997 to 2005 were analyzed and were prospectively followed to 31 December 2008. Patients' survival was determined using Cox proportional-hazards regression. RESULTS: We analyzed the survival of 2632 patients with DCM and 13,160 matched patients with DKD. The first year mortality rate was 11.9% in patients with DCM and 13.9% in patients with DKD. The incidence density rate of overall mortality was 11.2 per 100 patient-years in patients with DCM and 12.9 in patients with DKD. Patients with DKD had a worse survival than patients with DCM (P < 0.01). Compared to patients with DCM, the odds ratio (95% confidence interval [CI]) for first year mortality was 1.27 (1.10-1.47) and the hazard ratio for overall mortality was 1.18 (1.12-1.25) in patients with DKD. Patients' age, male gender, comorbid liver cirrhosis, higher fasting blood glucose, lower haematocrit, and lower serum phosphorus were independently associated with higher mortality. CONCLUSIONS: Patients with diabetes as primary kidney disease are associated with higher first year and overall mortality, compared to patients with diabetes as comorbidity in patients on maintenance haemodialysis.

Acute large-dose exposure to organophosphates in patients with and without diabetes mellitus: analysis of mortality rate and new-onset diabetes mellitus.

BACKGROUND: We investigated the mortality rates of patients with and without diabetes mellitus after acute large-dose exposure to organophosphate insecticides. All patients without diabetes mellitus were traced to examine the long-term risk of new-onset diabetes mellitus. Previous reports indicated that organophosphate exposure might increase the risk of new-onset diabetes mellitus. METHODS: We analyzed the records of 118 patients referred to Chang Gung Memorial Hospital for management of intentional organophosphate poisoning between 2000 and 2011. Patients were stratified by diabetes mellitus status. Demographic, clinical, laboratory and mortality data were analyzed. RESULTS: Most patients were middle aged (53.45 ± 16.20 years) and male (65.3%) and were referred to our hospital after a relatively short amount of time had elapsed since poisoning (median 3.0 hours). 18 (15.2%) of 118 patients died, including 15 (13.8%) of 109 patients without diabetes mellitus and 3 (33.3%) of 9 with diabetes mellitus. There was no significant difference in mortality between these groups (P = 0.117). In a multivariate Cox regression model, hypotension (P = 0.000), respiratory failure (P = 0.042), coma (P = 0.023), and corrected QT interval prolongation (P = 0.002) were significant risk factors for mortality. Conversely, diabetes mellitus status was not a significant variable in this model. At routine outpatient follow up a median of 1.25 months post exposure, random blood glucose measurements gave no evidence of new-onset diabetes in patients without pre-existing diabetes. CONCLUSIONS: Diabetes mellitus status might not increase mortality risk following acute large-dose exposure to organophosphates, and the risk of new-onset diabetes mellitus also might be minimal in the short term. Larger prospective studies with formal testing for diabetes at later times post-exposure are required.

Thymic epithelial ß-catenin is required for adult thymic homeostasis and function.

The role of ß-catenin in thymocyte development has been extensively studied, however, the function of ß-catenin in thymic epithelial cells (TECs) remains largely unclear. Here, we demonstrate a requirement for ß-catenin in keratin 5 (K5)-expressing TECs, which comprise the majority of medullary TECs (mTECs) and a progenitor subset for cortical TECs (cTECs) in the young adult thymus. We found that conditionally ablated ß-catenin in K5(+)-TECs and their progeny cells resulted in thymic atrophy. The composition of TECs was also aberrantly affected. Percentages of K5(hi)K8(+)-TECs, K5(+)K8(-)-TECs and UEA1(+)-mTECs were significantly decreased and the percentage of K5(lo)K8(+)-TECs and Ly51(+)-cTECs were increased in ß-catenin-deficient thymi compared with that in the control thymi. We also observed that ß-catenin-deficient TEC lineage could give rise to K8(+)-cTECs more efficiently than wild-type TECs using lineage-tracing approach. Importantly, the expression levels of several transcription factors (p63, FoxN1 and Aire), which are essential for TEC differentiation, were altered in ß-catenin-deficient thymi. Under the aberrant differentiation of TECs, development of all thymocytes in ß-catenin-deficient thymi was impaired. Interleukin-7 (IL-7) and chemokines (Ccl19, Ccl25 and Cxcl12) levels were also downregulated in the thymic stromal cells in the mutants. Finally, introducing a BCL2 transgene in lymphoid lineages, which has been shown to rescue IL-7-deficient thymopoiesis, partially rescued the thymic atrophy and thymocyte development defects caused by induced ablation of ß-catenin in K5(+)-TECs. Collectively, these findings suggest that ß-catenin is required for the differentiation of TECs, thereby contributing to thymocyte development in the postnatal thymus.

The role of physical activity in chronic kidney disease in the presence of diabetes mellitus: a prospective cohort study.

BACKGROUND/AIMS: Although the effect of exercise on health is well established, nephrologists seldom consider physical activity in the treatment of chronic kidney disease (CKD) or CKD in the presence of diabetes mellitus (DM/CKD). The aim of the present study was to analyze the benefits of leisure-time physical activity (LTPA) in DM/CKD. METHODS: A total of 445,075 adult participants who underwent a medical screening program between 1996 and 2008 were prospectively recruited. Of these, 7,863 DM/CKD subjects were identified. Each participant was categorized according to LTPA level (a product of duration and intensity) as inactive, low-active or fully active. Hazard ratios (HRs) for mortality risk were calculated. RESULTS: Fully active LTPA was associated with lower odds of DM/CKD development and lower risk of mortality among patients with DM/CKD in a dose-response relationship. The fully active and low-active DM/CKD groups had a 26% (HR 0.74, 95% CI 0.66-0.85) and 13% (HR 0.87, 95% CI 0.75-1.01) lower risk of all-cause mortality, respectively, in comparison to the inactive group. The association of exercise with mortality rate reduction was more pronounced among DM/CKD subjects (mortality rate reduction of 446.5 per 100,000 person-years) than among subjects with diabetes alone or CKD alone. CONCLUSION: Exercise, at the recommended level or more, is associated not only with lower odds of DM/CKD but also with a 26% lower mortality risk among DM/CKD patients. Nephrologists should encourage all DM/CKD subjects to be physically active

Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study.

BACKGROUND: Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women with hypertensive disorders during pregnancy. METHODS: We used insurance claims data from 1998 to 2009 to identify 26,651 women aged 19-40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213,397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors. RESULTS: Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09-12.4) and 12.4 (95% CI 8.54-18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76-4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43-20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20-15.7). INTERPRETATION: Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.

Comparing Survival between peritoneal dialysis and hemodialysis patients with subclinical peripheral artery disease: a 6-year follow-up.

Peripheral artery disease (PAD) is known to be an increased mortality risk in patients with end-stage renal disease (ESRD). The aim of this study was to compare patient survival between patients with subclinical PAD undergoing peritoneal dialysis (PD) and hemodialysis (HD). Subclinical peripheral artery was defined as an ankle-brachial index of less than 0.9. This study was conducted from April 2005, and the observation period ended on 30 June 2011. At the end of the follow-up, the status of all patients was assessed and data on mortality were obtained for the entire cohort. A total of 91 patients (61 HD and 30 PD) were included for analyses in this study. Mortality rate was 60.0% (18/30) for PD and 52.5% (32/61) for HD. Kaplan-Meier estimate demonstrate that PD patients had a higher mortality rate than those underwent HD (log-rank p = 0.0039). Cox regression model demonstrated that PD was an independent predictor for further mortality in ESRD patients with subclinical peripheral artery disease.(p = 0.012, HR: 1.776, 95% CI: 1.136-2.775). In multivariate analysis, the HD group still had a greater survival than PD group (p = 0.005, HR:1.916, 95% CI: 1.218-3.015). In patients with subclinical peripheral artery disease, the patient survival is better in HD patients as compared with PD patients.

Paraquat poisoning in pediatric patients.

OBJECTIVE: This observational study examined the outcome of Taiwanese pediatric patients with paraquat poisoning and compared these data with the published data on paraquat poisonings from other international poisoning centers. METHODS: We performed a retrospective study on children with acute paraquat poisoning that were admitted to the Chang Gung Memorial Hospital during a period of 10 years (2000-2010). Of the 193 paraquat poisoning patients, only 6 were children. RESULTS: The mean age was 8.85 ± 5.55 (1-15.6) years. Younger patients had accidentally swallowed paraquat, whereas older patients had intentionally ingested paraquat. Most patients were referred within a relatively short period (0.5-2.0 hours). Paraquat poisoning was associated with high morbidity and often resulted in severe complications, including acute respiratory distress syndrome and multiple-organ failure. The complications included shock (50.0%), hypoxemia (33.3%), respiratory failure (33.3%), nausea/vomiting (16.7%), abdominal pain (33.3%), hepatitis (66.7%), gastrointestinal tract bleeding (33.3%), acute renal failure (33.3%), and seizures (16.7%). Patients were treated aggressively with a standard detoxification protocol consisting of gastric lavage, active charcoal, charcoal hemoperfusion, and cyclophosphamide and steroid pulse therapies. Secondary bacterial infections were common after hospitalization and included sepsis (33.3%), pneumonia (33.3%), and urinary tract infection (50.0%). In the end, 2 patients (33.3%) died from multiple-organ failure, despite intensive resuscitation. CONCLUSIONS: Our data (mortality rate, 33.3%) are comparable to the data of other published reports from other international poison centers. Evidently, a prompt diagnosis of paraquat poisoning and an immediate institution of a detoxification protocol is a prerequisite for a favorable outcome.

Real-time PCR analysis of the intestinal microbiotas in peritoneal dialysis patients.

Bifidobacterium and Lactobacillus can beneficially affect the host by producing acetic acid and lactic acid, which lower pH and thereby inhibit the growth of pathogens or allow the probiotic bacteria to compete with pathogens for epithelial adhesion sites and nutrients. The transmural migration of enteric organisms into the peritoneal cavity can cause peritonitis in peritoneal dialysis (PD) patients. We hypothesized that the composition of the intestinal microbiota with regard to Lactobacillus species and Bifidobacterium species differed between PD patients and healthy controls. The aim of the study was to investigate these differences by real-time PCR analysis of fecal samples. From 1 August 2009 to 31 March 2010, a total of 29 nondiabetic PD patients and 41 healthy controls from China Medical University Hospital were recruited after giving their informed consent. Fecal samples were collected from the PD patients and their age-matched counterparts in the morning using a standardized procedure. DNA extracted from these samples was analyzed by real-time PCR. All bifidobacteria, Bifidobacterium catenulatum, B. longum, B. bifidum, Lactobacillus plantarum, L. paracasei, and Klebsiella pneumoniae were less frequently detected in the patient samples. Dysbiosis (microbial imbalance) may impair intestinal barrier function and increase host vulnerability to pathogen invasion. Further studies are necessary to confirm our findings before clinical trials with probiotic supplementation in PD patients.

The risk for chronic kidney disease in patients with heart diseases: a 7-year follow-up in a cohort study in Taiwan.

BACKGROUND: The worldwide increasing trend of chronic kidney disease (CKD) is of great concern and the role of heart disease deserves longitudinal studies. This study investigated the risk of developing CKD among patients with heart diseases. METHODS: From universal insurance claims data in Taiwan, we retrospectively identified a cohort of 26005 patients with newly diagnosed heart diseases and 52010 people without such disease from the 2000-2001 claims. We observed prospectively both cohorts until the end of 2007 to measure CKD incidence rates in both cohorts and hazard ratios (HR) of CKD. RESULTS: The incidence of CKD in the cohort with heart disease was 4.1 times greater than that in the comparison cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37 (95% confidence interval (CI)=2.05-2.74) in the multivariate Cox proportional hazard model after controlling for sociodemographic characteristics and comorbidity. Compared with individuals aged<40 years, the HRs for CKD ranged from 2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD observed in our patients were also independently associated with hypertension (HR=2.26, 95% CI=1.94-2.63) and diabetes mellitus (HR=2.44, 95% CI=2.13-2.80), but not with hyperlipidemia (HR=1.13, 95% CI=0.99-1.30). CONCLUSIONS: This population study provides evidence that patients with heart disease are at an elevated risk of developing CKD. Hypertension and diabetes mellitus are also comorbidity associated with increasing the CKD risk independently.

Hypertensive disorders in pregnancy and preterm delivery and subsequent stroke in Asian women: a retrospective cohort study.

BACKGROUND AND PURPOSE: Few studies exist concerning the risk of stroke associated with hypertensive disorders in pregnancy (HDP) in Asian women. This study investigates whether preterm delivery further complicates this risk in women with HDP in Taiwan. METHODS: Based on universal insurance claims data, 1092 pregnant women with newly diagnosed HDP from 2000 to 2004 and aged 15 to 40 years were identified as the HDP cohort. Then, 4715 randomly selected persons without HDP frequency matched with the index year were designated as the non-HDP controls. Both cohorts were followed-up until the end of 2008 to measure the incidence of stroke. RESULTS: The HDP cohort had a higher incidence of stroke than the non-HDP cohort (30.1 vs 12.8 per 10 000 person-years), with an overall adjusted hazard ratio of 2.04 (95% CI, 1.18- 3.51) for stroke. Preterm delivery increased the risk of stroke to 3.22-fold (95% CI, 1.48-6.99; P for trend=0.002). The age-specific V-shape risk association showed that the highest risk of stroke was noted among subjects 15 to 18 years old in the HDP group (hazard ratio, 13.4; 95% CI, 1.54-116.7) and followed by women aged 35 years and older (hazard ratio, 5.56; 95% CI, 1.47-21.0). CONCLUSIONS: Pregnant women with HDP have an increased risk of subsequent stroke. Preterm delivery and older ages increase the risk of subsequent stroke. Adolescents with HDP also have an elevated risk of stroke. Early identification of women with HDP is needed for prevention.

Nutritional status of vegetarians on maintenance haemodialysis.

AIM: Vegetarian diets have long been thought of as beneficial to health. However, vegetarian diets are often low in protein, which is contradictory to the high protein diet guideline for uraemia patients. The purpose of the study was to investigate the impact of a vegetarian diet on the nutritional status of haemodialysis (HD) patients. METHODS: Patients on chronic HD for over 6 months were included in the study. The normalized protein catabolic rate (nPCR) was used to reflect daily protein intake. Biochemical markers of nutrition, anthropometric parameters, subjective global assessment (SGA) and functional activity of daily living were assessed to evaluate the nutritional status of vegetarians on chronic HD. RESULTS: Nineteen out of 318 HD patients were vegetarians. The nPCR was lower in the vegetarian group (1.20 ± 0.24 vs 1.10 ± 0.29 g/kg per day, non-Veg vs Veg, P < 0.05). The serum albumin and prealbumin were similar in vegetarian and non-vegetarian HD patients. The body mass index (BMI) and mid-arm muscular circumference (MAMC) were lower in vegetarian patients (P < 0.05). The haematocrit of vegetarians can be maintained at a level similar to that of non-vegetarian patients but erythropoietin doses needed were higher in vegetarian patients (P < 0.05). The muscle strength evaluated by the hand-grip test, SGA and activities of daily living were similar in vegetarians and non-vegetarians. CONCLUSION: The present study revealed that HD patients on vegetarian diets might have a smaller BMI, but SGA and function of daily activities were similar to those of the non-vegetarians. The haematocrit of vegetarians can be maintained with a higher erythropoietin dose.

Long-term use of fenofibrate is associated with increased prevalence of gallstone disease among patients undergoing maintenance hemodialysis.

BACKGROUND: In spite of insufficient evidence to guide the use of lipid-lowering drugs (LLDs) among the dialysis population, these drugs are frequently used to treat dyslipidemia. Several studies have found that long-term use of LLDs is associated with an increased risk of gallstone disease (GSD) in the general population. However, the lithogenic risk of LLDs in patients undergoing hemodialysis (HD) has not been studied. AIM: It is to assess the influence of long-term use of LLDs on the prevalence of GSD among patients undergoing HD. METHODS: This cross-sectional study included 108 eligible patients receiving maintenance HD: 35 receiving lovastatin; 34 fenofibrate; and 39 no LLD. GSD was defined as the presence of gallstones or the performance of cholecystectomy while taking LLD. Abdominal ultrasonography, demographic parameters, and laboratory data were obtained for all enrolled subjects. ANOVA with Bonferroni's test and chi-square test were used to compare differences among the three groups. RESULTS: The three groups had similar clinical characteristics with regard to age, gender, duration of HD, body mass index, and total cholesterol values. However, a significantly higher prevalence of GSD and higher triglyceride levels were found in patients receiving fenofibrate, compared with those in other groups (p < 0.05). Among dialysis patients on fenofibrate, increased age, female gender, larger daily dose, and longer duration of treatment were associated with increased risks for GSD. CONCLUSIONS: Our study shows that long-term use of fenofibrate is related to increased risk of GSD among HD patients. Further large-scale studies are needed to confirm our findings.

Prophylactic use of omeprazole associated with a reduced risk of peptic ulcer disease among maintenance hemodialysis patients.

BACKGROUND: Patients undergoing maintenance hemodialysis (MHD) have a high prevalence of peptic ulcer disease (PUD). Omeprazole is a proton pump inhibitor with proven efficacy in the prevention and treatment of PUD. However, there is little data on the prophylactic use of omeprazole in reducing the risk of PUD among MHD patients. METHODS: This prospective study included 93 patients undergoing MHD at Zen-Ho Dialysis Center between July 2008 and December 2009. Fifty-three patients were assigned to receive 20 mg of omeprazole daily for 18 months and 40 patients served as control. The Kaplan-Meier method was applied to calculate the cumulative incidence of PUD. RESULTS: The per-protocol population comprised 85 patients (omeprazole group, 49; control group, 36). Both groups had similar baseline characteristics. The need for endoscopy was found to be significantly less (10.2 vs. 44.4%, p = 0.001) in the omeprazole group than in the control group. Dialysis patients in the omeprazole group required fewer blood transfusions and erythropoietin doses than did the control group patients. Kaplan-Meier analysis revealed a higher cumulative ulcer rate in the control group (log-rank test, p = 0.04). However, omeprazole did not reduce the risk of PUD in MHD patients on regular aspirin or warfarin. CONCLUSIONS: We conclude that prophylactic use of omeprazole might be effective to lower the incidence of PUD among MHD patients without regular aspirin or warfarin use. Further large-scale controlled trials should be carried out to confirm our findings.

Cytokine changes in fatal cases of paraquat poisoning.

Cytokine-mediated inflammation is involved in the pathophysiology of paraquat toxicity. Nevertheless, few human studies have examined fluctuations in circulating cytokine levels. Blood samples were obtained from 21 patients with paraquat poisoning and compared to those of 18 healthy controls. All paraquat patients received a standard detoxification protocol composed of hemoperfusion, pulse therapies of methylprednisolone and cyclophosphamide, followed by dexamethasone therapy. Nonsurvivors not only had higher scores for the severity index of paraquat poisoning (P=0.004) but also presented with higher white blood cell counts (P=0.046) than survivors. Multiplex immunoassays revealed higher circulating levels of interleukin 2 (IL-2), interleukin 9 (IL-9), interleukin 10 (IL-10) and macrophage inflammatory protein-1 beta (MIP-1ß) in survivors than in healthy controls. Furthermore, the circulating levels of interleukin 1 beta (IL-1ß), IL-2, interleukin 5 (IL-5), interleukin 8 (IL-8), IL-9, IL-10, interleukin 12 (IL-12 p70), interleukin 17A (IL-17A), eotaxin, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and MIP-1ß were higher in nonsurvivors than in healthy controls. Finally, the circulating levels of IL-1ß and MCP-1 were higher in nonsurvivors than in survivors. Therefore, the observation of cytokine-mediated inflammation is in line with the detoxification protocol because glucocorticoids and cyclophosphamide are potent anti-inflammatory agents. Additionally, circulating levels of IL-1ß and MCP-1 could serve as promising prognostic markers for patients with paraquat poisoning.