Nephrotoxicity of organophosphate flame retardants in patients with chronic kidney disease: A 2-year longitudinal study.

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.

Update on the Application of Ultrasonography in Understanding Autosomal Dominant Polycystic Kidney Disease.

With an estimated prevalence of 1 in 1000 individuals globally, autosomal dominant polycystic kidney disease (ADPKD) stands as the most prevalent inherited renal disorder. Ultrasonography (US) is the most widely used imaging modality in the diagnosis and monitoring of ADPKD. This review discusses the role of US in the evaluation of ADPKD, including its diagnostic accuracy, limitations, and recent advances. An overview of the pathophysiology and clinical manifestations of ADPKD has also been provided. Furthermore, the potential of US as a noninvasive tool for the assessment of disease progression and treatment response is examined. Overall, US remains an essential tool for the management of ADPKD, and ongoing research efforts are aimed at improving its diagnostic and prognostic capabilities.

Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History.

OBJECTIVE: To test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history. DESIGN: Prospective cross-sectional study. SETTING: Largest medical center in southern Taiwan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states. PARTICIPANTS: A total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125). RESULTS: Plantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71). CONCLUSIONS: FOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.

Is regular in-person recall superior to non-regular in-person recall in clinical outcomes among new patients undergoing peritoneal dialysis.

OBJECTIVE: To investigate the different impacts on clinical outcomes between regular recall and non-regular recall among incident peritoneal dialysis (PD) patients. METHODS: A two-center cohort of 216 new PD patients from 1January 2013, to 31 December 2014, was studied. Informative clinical data were collected from baseline until two years after PD initiation, including demographics, laboratory and PD-related parameters, PD-related peritonitis rates, and frequency of hospitalization. Regular in-person recall (RPR) was defined as having a one-month interval and non-regular in-person recall (NRPR) as an interval ranging from more than one month to less than three months. RESULTS: Percentage of patients with peritonitis was significantly higher among patients in the NRPR group than among those in the RPR group (27.7% vs. 16.5%, p = .049). PD-related peritonitis rate was higher in the NRPR vs. RPR cohorts (0.16 vs. 0.09 person/year, p = .019). PD-related hospitalization frequency was also higher in the NRPR cohort (0.8 ± 1.0 vs. 0.5 ± 0.9, p = .039) over two years. Kt/V values in the NRPR cohort gradually decreased over two years and were at lower levels than in the RPR cohort. CONCLUSIONS: New PD patients with NRPR showed higher rates of PD-related peritonitis and hospitalization frequency than patients with RPR.

Hemogram parameters can predict in-hospital mortality of patients with Myasthenic crisis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease involving the neuromuscular junction. Myasthenic crisis (MC), which is characterized by respiratory failure and the requirement of mechanical ventilation in patients with MG, is still a medical emergency despite the decrease in mortality with the advances in acute management. Hemogram is a cost-effective test for evaluating hematological complications and systemic inflammation, and hemogram data have been used to predict various clinical outcomes of several diseases. The relationship between hemogram and MG has been discussed, but the role of hemogram data in predicting the prognosis of MC patients has not been established. METHODS: To identify whether hemogram data can predict in-hospital mortality in patients with MC, we retrospectively investigated 188 myasthenic crisis events from the Chang Gung Research Database between April 2001 and March 2019. Demographic and clinical characteristics were collected, as well as hemogram data before intubation and extubation. The endpoints were mortality during mechanical ventilation and mortality after extubation. RESULTS: The overall in-hospital mortality rate was 22%. Multivariate logistic regression analysis for predicting mortality during mechanical ventilation showed that old age at MC onset (OR = 1.039, p = 0.022), moderate-to-severe anemia (OR = 5.851, p = 0.001), and extreme leukocytosis (OR = 5.659, p = 0.022) before intubation were strong predictors of mortality, while acute management with plasma exchange or double-filtration plasmapheresis (PE/DFPP) significantly decreased mortality (OR = 0.236, p = 0.012). For predicting mortality after extubation, moderate-to-severe anemia before extubation (OR = 8.452, p = 0.017) and non-treated with disease-modifying therapy before MC (OR = 5.459, p = 0.031) were crucial predictive factors. CONCLUSION: This study demonstrated that both old age at MC onset and moderate-to-severe anemia are important predictors of in-hospital mortality in patients with MC, and extreme leukocytosis is another crucial predictor of mortality during mechanical ventilation. The suggested mechanism is that anemia-induced hypoxia may enhance the release of proinflammatory cytokines, exacerbate systemic inflammation, and lead to multiple organ dysfunction syndrome and, finally, mortality.

Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes.

BACKGROUND: Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. METHODS: The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value). RESULTS: A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS. CONCLUSIONS: Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.

Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.

Decreased cerebral blood flow and improved cognitive function in patients with end-stage renal disease after peritoneal dialysis: An arterial spin-labelling study.

OBJECTIVES: The aim of this study was to evaluate the relationship between cognitive impairment and brain perfusion using arterial spin labelling (ASL) in end-stage renal disease (ESRD) patients undergoing PD. METHODS: ESRD patients undergoing PD were recruited. Laboratory screening, neuropsychological tests and ASL magnetic resonance imaging (MRI) were conducted prior to and after 6 months of PD. Age- and sex-matched normal subjects without ESRD served as the control group. Comparisons of regional CBF between ESRD patients before or after undergoing PD and normal controls were performed. Correlations between biochemical, neuropsychological and CBF data were also conducted to evaluate the relationships. RESULTS: ESRD patients showed poor performance in many of the neuropsychological tests; PD improved cognition in some domains. Pre-PD patients had higher mean CBF than post-PD patients and normal controls, but no significant difference was found between the normal controls and post-PD patients. Negative correlations were observed pre-PD (regional CBF in left hippocampus vs. perseverative responses, r = -0.662, p = 0.014), post-PD (mean CBF vs. haemoglobin level, r = -0.766, p = 0.002), and before and after PD (change in CBF in the left putamen vs. change in haematocrit percentage, r = -0.808, p = 0.001). CONCLUSION: Before PD, ESRD patients had increased cerebral perfusion that was related to poorer executive function, especially in the left hippocampus. Post-PD patients performed better in some cognitive test domains than pre-PD patients. The degree of anaemia, i.e., haemoglobin level or haematocrit percentage, might predict cognitive impairment in PD patients. KEY POINTS: • In this study, ESRD patients before PD had cerebral hyperperfusion that was related to poorer executive function. • Post-PD patients performed better in some cognitive test domains than pre-PD patients did. • The degree of anaemia might predict cognitive impairment in PD patients.

Effects of Peritoneal Dialysis on Clinical Factors and Functional Performance.

BACKGROUND: We investigated the longitudinal trend of functional performance in peritoneal dialysis (PD) patients over 1 year after PD commencement and its related clinical parameters. METHODS: One hundred and ninety-six PD patients were enrolled in this study. Karnofsky Performance Status Scale(KPSS) scores were used to assess functional performance. Patients were stratified into 3 groups according to the changes in KPSS from baseline to 1 year. A logistic regression analysis was performed to examine the associations of clinical parameters with KPSS changes. RESULTS: Patients with KPSS declined showed older age and higher serum albumin concentration reduction within 1 year than those in KPSS improved and stable changes. Age was the significant risk factor for KPSS decline, while male and diabetes were significantly associated with non-declined KPSS by multivariable logistic regression analysis. CONCLUSION: The main determinants of KPSS trend were age, sex, and diabetes in new PD patients.

Time-varying serum albumin levels and all-cause mortality in prevalent peritoneal dialysis patients: a 5-year observational study.

BACKGROUND: In this study, we investigated the association of time-varying serum albumin levels with mortality over a 5-year period in one cohort of patients undergoing long-term peritoneal dialysis (PD) therapy. METHODS: The participants in this study enrolled 302 patients who underwent long-term PD at a single PD center in Taiwan. We reviewed medical records from 2011 to 2015 retrospectively. Time-averaged albumin level and serum albumin reach rate (defined as the percentage of serum albumin measurements that reached ≥3.5 g/dL) were applied as the predictor variables in the first 2 years (2011-2012). All-cause mortality was used as the outcome variable in the subsequent 3 years (2013-2015). Hazard function of all-cause mortality in the study participants was examined by using Cox proportional hazard regression models . RESULTS: Patients with different albumin reach rates (75-< 100%, 50-< 75%, 1-< 50%) did not exhibit a significantly increased risk for all-cause mortality. Patients with a 0% albumin reach rate exhibited a significantly increased risk for all-cause mortality (hazard ratio [HR] 7.59, 95% confidence interval [CI], 2.38-24.21) by fully adjusted analysis. Patients with time-averaged albumin levels of < 3.5 g/dL (HR 15.49, 95% CI 1.74-137.72) exhibited a higher risk for all-cause mortality than those with serum albumin levels ≥4.0 g/dL. CONCLUSIONS: This study demonstrated that higher serum albumin reach rates and higher time-averaged serum albumin levels are associated with a lower mortality rate over a 5-year period among patients undergoing long-term PD.

Increased circulating endothelial progenitor cells and improved short-term outcomes in acute non-cardioembolic stroke after hyperbaric oxygen therapy.

BACKGROUND: Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity. METHODS: The numbers of circulating EPCs [CD133+/CD34+ (%), KDR+/CD34+ (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT). The biomarkers and clinical scores were compared with those of 25 age- and sex-matched disease controls. RESULTS: The numbers of KDR+/CD34+ (%) in the HBOT group following HBOT increased significantly, whereas the numbers of CD133+/CD34+ (%) also showed a tendency to increase without statistical significance. The mean high-sensitivity C-reactive protein levels showed significant decrease post-HBOT follow-up in the HBOT group. The changes in KDR+/CD34+EPC (%) numbers were positively correlated with changes in clinical outcomes scores (BI, NIHSS, and MRS) in the HBOT group. CONCLUSIONS: Based on the results of our study, HBOT can both improve short-term clinical outcomes and increase the number of circulating EPCs in patients with acute non-cardioembolic stroke.

Association between Extreme Values of Markers of Chronic Kidney Disease: Mineral and Bone Disorder and 5-Year Mortality among Prevalent Hemodialysis Patients.

BACKGROUND/AIMS: We examined the association between markers of chronic kidney disease - mineral and bone disorder (CKD-MBD) and mortality in hemodialysis (HD) patients. METHODS: We retrospectively reviewed the association between markers of CKD-MBD and mortality in 1,126 HD patients from 2009 to 2013 with baseline (B), time-average (TA), and time-dependent (TD) Cox regression models. RESULTS: Hypercalcemia (10.9-11.9 mg/dL) indicated an increased risk of all-cause mortality (TA: hazard ratio [HR] 3.49; p = 0.01). Hypophosphatemia (2.0-2.5 mg/dL) was significantly associated with an increased risk of all-cause mortality (TA: HR 5.18; p = 0.01). Hypophosphatemia (<2.0 mg/dL) was significantly associated with an increased risk of cardiovascular mortality in all models. Intact parathyroid hormone levels <60 and >1,500 pg/mL indicated an increased risk of all-cause mortality (TA: HR 1.64; p = 0.02; TD: HR 2.26; p = 0.02). CONCLUSION: Extreme values of CKD-MBD markers are associated with mortality risk in HD patients. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=478972.

Viridans streptococcus peritonitis in peritoneal dialysis: clinical characteristics and comparison with concurrent polymicrobial infection.

BACKGROUND: The clinical course of Viridans streptococci (VS) peritonitis in patients undergoing peritoneal dialysis (PD) is rarely reported. This study examined the association of clinical factors with VS peritonitis. METHODS: We retrospectively reviewed clinical data from patients with VS peritonitis from March 1990 to February 2016 in a PD center in Taiwan and evaluated clinical profiles and treatment outcomes. RESULTS: A total of 109 episodes of VS peritonitis in 71 patients identified. Among these patients, 57 had mono-VS peritonitis and 14 had concurrent polymicrobial infections. The median time interval from PD initiation to the first VS peritonitis episode was 18 months (range, 0.6-144 months). Among clinical outcomes, most VS peritonitis episodes were completely cured regardless of a history of peritonitis. All episodes with catheter removal occurred in those without a history of recent antibiotic use. CONCLUSION: VS peritonitis in patients undergoing PD typically has favorable treatment outcomes. Antibiotic therapy should be started promptly.

Longitudinal analysis of cardiac structure and function in incident-automated peritoneal dialysis: comparison between icodextrin solution and glucose-based solution.

BACKGROUND: This study aimed to evaluate the longitudinal changes in cardiac structure and function in incident-automated peritoneal dialysis (APD) patients. METHODS: We conducted a 2-year prospective, randomized, open-label, parallel-group study to compare the efficacy of icodextrin solution versus glucose-based solution. Echocardiography was performed at baseline, 1 and 2 years. Echocardiographic parameters over 2 years were evaluated for each group, using the Friedman test. Generalized linear regression analysis was used to test the associations between baseline clinical variables and echocardiographic changes, and a multivariate model was used to analyze cardiac function between the two groups. RESULTS: A total of 43 APD patients were enrolled in the beginning of this study. Twenty patients in the icodextrin group (ICO) and 18 patients in the glucose group (GLU) completed the study. In left ventricular (LV) systolic function measurements, ejection fraction (EF) increased significantly in the GLU group. Measurements of LV diastolic function and septal early mitral annulus velocity (EMV) increased significantly from baseline to 24-months in the ICO group (5.43-5.51 ms). The GLU group showed a significant decrease in peak early diastolic velocity (EDV) (70.67-68.25 cm/s), but a significant increase in septal EMV (5.94-7.57 ms) from baseline to 24-months. No significant association was found between the baseline clinical variables and echocardiographic changes within 24 months in the generalized linear regression analysis. Multivariate models were used to investigate changes in the four primary endpoints, namely, myocardial performance index (MPI), left ventricular ejection fraction (LVEF), deceleration time (DT), and E/e' ratio. These primary endpoints show no significant association with the baseline values in both the ICO and GLU groups. CONCLUSION: The present study demonstrates that long-dwell icodextrin solution can maintain reasonable cardiac structure and function in incident-APD patients. TRIAL REGISTRATION: ISRCTN14931270 (retrospectively registered on 23/03/2018).

Impact of inflammation and oxidative stress on carotid intima-media thickness in obstructive sleep apnea patients without metabolic syndrome.

Obstructive sleep apnea (OSA) increases the risk of cardiovascular diseases, and carotid intima-media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. This study tested the hypothesis that inflammation and oxidative stress determined carotid IMT in patients with OSA. The carotid IMT, mean systolic and diastolic pressure (night and morning) were significantly higher and the level of thiols and high-density lipoprotein were significantly lower in our 121 OSA patients than in 27 controls (P < 0.05). The apnea/hypopnea index was correlated positively with E-selectin (r = 0.222, P = 0.014), total cholesterol (r = 0.185, P = 0.042), low-density lipoprotein (r = 0.264, P = 0.003) and HbA1c levels (r = 0.304, P = 0.001), but inversely with high-density lipoprotein level (r = -0.203, P = 0.025) in the 121 patients with OSA. In OSA subjects, multiple linear regression analysis revealed that age, systolic blood pressure and intercellular cell adhesion molecule-1 level associated independently with carotid IMT. Besides both age and systolic blood pressure, our study demonstrated that intercellular cell adhesion molecule-1 level was associated significantly with carotid IMT in those patients who had OSA but without metabolic syndrome.

Serum Alkaline Phosphatase Levels are Not Associated with Increased Death Risk in Prevalent Hemodialysis Patients: 5-Year Experience in a Single Hemodialysis Center.

BACKGROUND/AIMS: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. METHODS: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. RESULTS: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. CONCLUSION: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.

Serum Potassium Profile and Associated Factors in Incident Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Abnormal potassium profiles are common in peritoneal dialysis (PD) patients. We studied the factors associated with serum potassium profiles in incident PD patients. METHODS: Patients were enrolled from two hospital-facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. RESULTS: There were 168 men and 151 women (mean age, 50.8 years). Blood urea nitrogen (BUN), creatinine (Cr), and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01-1.03, p = 0.001) and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029) levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. CONCLUSION: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients.

An association between time-varying serum albumin level and the mortality rate in maintenance haemodialysis patients: a five-year clinical cohort study.

BACKGROUND: Until now, no long-term studies relating serum albumin level to mortality rate in prevalent haemodialysis (HD) patients have been conducted. We aimed to examine the association between serum albumin level and mortality over a 5-year period. METHODS: This study included 781 patients who received maintenance HD in a large, hospital-facilitated HD centre. Five-year medical records (2009-2013) were retrospectively reviewed, and the cut-off level for serum albumin level was set at 3.5 g/dL. The analysed albumin levels were expressed as time-averaged levels (first 24-month data) and albumin target reach rate over the first 2-year interval. Univariate and multivariate Cox proportional hazard regression models were used to examine the hazard function of the all-cause and cardiovascular mortality of the study participants in the subsequent 3-year period (2011-2013). RESULTS: Compared to those with a 100 % albumin reach rate (3.5 g/dL), the participants with 75- < 100, 50- < 75, and 1- < 50 % albumin reach rates exhibited significantly increased risk for all-cause mortality (HR 1.72, 95 % CI 1.19-2.47; HR 3.14, 95 % CI 1.91-5.16; HR 3.66, 95 % CI 2.18-6.16, respectively). A similar trend for all-cause mortality was demonstrated in participants with time-averaged albumin levels <4 g/dL (HR 1.57, 95 % CI 1.00-2.46 for 3.5-4.0 g/dL; HR 3.66, 95 % CI 2.11-6.32 for <3.5 g/dL). Compared to a 100 % albumin reach rate, the 50- < 75 and 1- < 50 % groups (HR 4.28, 95 % CI 1.82-10.01; HR 3.23, 95 % CI 1.22-8.54 respectively) showed significantly higher cardiovascular mortality rates. Similarly, participants with a time-averaged serum albumin level <3.5 g/dL exhibited a higher risk for cardiovascular mortality (HR 3.24, 95 % CI: 1.23-8.56). CONCLUSIONS: This long-term study demonstrated that higher reach rates of serum albumin levels and higher time-averaged serum albumin levels are associated with a lower mortality rate in patients undergoing maintenance HD.

Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic Lupus erythematosus.

BACKGROUND: This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE). METHODS: Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated. RESULTS: The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05). CONCLUSIONS: The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.

Predictors and long-term outcome of seizures in human immuno-deficiency virus (HIV)-negative cryptococcal meningitis.

BACKGROUND: Seizures are one of the most important neurologic complications of human immuno-deficiency virus (HIV)-negative cryptococcal meningitis. A better understanding of the risk associated factors can help predict those who will require treatment. METHODS: This 22-year retrospective study enrolled 180 patients. Prognostic variables independently associated with seizures or fatality were analyzed using stepwise logistic regression. RESULTS: Twenty-eight patients with HIV-negative cryptococcal meningitis had seizures, including 13 with early seizures and 15 with late seizures. The mean time interval from HIV-negative cryptococcal meningitis to first seizure in the early and late seizure groups were 1.5 and 51.4 days, respectively. Nine out of the 28 cases (32%) occurred within 24 hours of presentation. The overall mortality rate was 54% (15/28) and two patients progressed to epilepsy. CONCLUSIONS: Patients with seizure have worse outcomes and longer hospitalization. Most first seizures occur within one year after the diagnosis of HIV-negative cryptococcal meningitis.