Effects of lanthanum carbonate and calcium carbonate on fibroblast growth factor 23 and hepcidin levels in chronic hemodialysis patients.

BACKGROUND: Phosphate binders have an impact on fibroblast growth factor 23 (FGF23); however, the effect of phosphate binders on serum hepcidin has not been explored. We conducted a 24-week multicenter randomized controlled trial to investigate the effects of lanthanum carbonate or calcium carbonate monotherapy on serum phosphate, FGF23, and hepcidin levels in chronic hemodialysis patients. METHODS: Forty-six patients were recruited, and daily dietary phosphorus was controlled between 600-800 mg. Serum calcium, phosphate, albumin, alkaline phosphatase (ALP), FGF23, intact parathyroid hormone (iPTH), hepcidin, high-sensitivity CRP (hsCRP), 25(OH)D, 1,25(OH)2D, fetuin-A, and osteopontin were checked as scheduled. RESULTS: Twenty-five patients completed the study. Mean serum FGF23 level was significantly decreased after a 24-week treatment with lanthanum (8677.5 ± 7490.0 vs. 4692.8 ± 5348.3 pg/mL, p = 0.013, n = 13), but not with calcium (n = 12). The reduction of serum hepcidin in lanthanum group was positively correlated with the decrement of serum phosphate (r = 0.631, p = 0.021) and serum hsCRP (r = 0.670, p = 0.012) levels, respectively. Serum ALP, iPTH, vitamin D, fetuin-A, and osteopontin revealed no significant inter- or intragroup differences. CONCLUSIONS: In summary, a decrease in serum FGF23 levels and a trend of decline in hepcidin levels were observed only in lanthanum group.

Impact of metabolic syndrome and its components on heart rate variability during hemodialysis: a cross-sectional study.

BACKGROUND: Both uremia and metabolic syndrome (MetS) affect heart rate variability (HRV) which is a risk factor of poor prognoses. The aim of this study was to evaluate the impact of MetS on HRV among chronic hemodialysis patients. METHODS: This cross-sectional study was carried out in a teaching hospital in Northern Taiwan from June to August, 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled. HRV were measured for 4 times on the index hemodialysis day (HRV-0, -1, -2, and -3 at before, initial, middle, and late phases of hemodialysis, respectively), and the baseline demographic data and clinical parameters during the hemodialysis session were documented. Then we evaluated the impacts of MetS and its five components on HRV. RESULTS: One hundred and seventy-five patients (100 women, mean age 65.1 ± 12.9 years) were enrolled and included those with MetS (n = 91, 52 %) and without MetS (n = 84, 48 %). The patients with MetS(+) had significantly lower very low frequency, total power, and variance in HRV-0, total power and variance in HRV-2, and variance in HRV-3. (all p ≦ 0.05) When using the individual components of MetS to evaluate the impacts on HRV indices, the fasting plasma glucose (FPG) criterion significantly affected most indices of HRV while other four components including "waist circumference", "triglycerides", "blood pressure", and "high-density lipoprotein" criteria exhibited little impacts on HRV. FPG criterion carried the most powerful influence on cardiac ANS, which was even higher than that of MetS. The HRV of patients with FPG(+) increased initially during the hemodialysis, but turned to decrease dramatically at the late phase of hemodialysis. CONCLUSIONS: The impact of FPG(+) outstood the influence of uremic autonomic dysfunction, and FPG criterion was the most important one among all the components of MetS to influence HRV. These results underscored the importance of interpretation and management for abnormal glucose metabolism.

Heart rate variability is an indicator for intradialytic hypotension among chronic hemodialysis patients.

BACKGROUND: Intradialytic hypotension (IDH) carries adverse impact. Heart rate variability (HRV) represents autonomic cardiac regulation which influences intradialytic blood pressure. We aimed to evaluate the association between IDH and HRV. METHODS: This prospective study was carried out in a teaching hospital in Taiwan from June to August 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled and received HRV measurements for 4 times (before and during an index hemodialysis session). Patients were categorized by the changes of systolic blood pressure during the index hemodialysis into Group 1 (elevation >20 mmHg), Group 2 (decrease >20 mmHg), and Group 3 (others). Then we compared HRV indices among the three groups, and determined the indicators for IDH. RESULTS: One hundred and seventy-one patients (96 women, mean age 64.9 years) were enrolled and categorized into Group 1 (n = 47, 27.5 %), Group 2 (n = 45, 26.3 %) and Group 3 (n = 79, 46.2 %). Comparing with Group 1 and/or Group 3, Group 2 had significantly higher blood pressure at hemodialysis initiation (most p < 0.001) and statistically lower levels of HRV indices including variance, total power, very low-frequency, low-frequency and high-frequency since the middle phase of the hemodialysis. By logistic regression method, higher systemic blood pressure [odds ratio (OR) 1.048; p < 0.001], heart rate (OR 1.093; p = 0.021), low-frequency/high-frequency ratio (OR 1.715; p = 0.022), as well as lower variance (OR 0.639; p = 0.048) at hemodialysis initiation were independently associated with intradialytic blood pressure changes. CONCLUSIONS: HRV is a useful indicator for IDH among hemodialysis patients.

Factors associated with emergency department visit within 30 days after discharge.

BACKGROUND: Post-discharge care remains a challenge because continuity of care is often interrupted and adverse events frequently occur. Previous studies have focused on early readmission but few have investigated emergency department (ED) visit after discharge. METHODS: This retrospective observational study was conducted between April 2011 and March 2012 in a referral center in Taiwan. Patients discharged from the general medical wards during the study period were analyzed and their characteristics, hospital course, and associated factors were collected. An ED visit within 30 days of discharge was the primary outcome while readmission or death at home were secondary outcomes. RESULTS: There were 799 discharged patients analyzed, including 96 (12 %) with an ED visit of 12.4 days post-discharge and 111 (14 %) with readmissions at 13.3 days post-discharge. Sixty patients were admitted after their ED visit. Underlying chronic illnesses were associated with 72 % of ED visits. By multivariate analysis, Charlson score and the use of naso-gastric tube were independent risk factors for ED visit within 30 days after discharge. CONCLUSIONS: Early ED visit after discharge is as high as 12 %. Patients with chronic illness and those requiring a naso-gastric tube or external biliary drain are at high risk for post-discharge ED visit.

Identification of immune-related biomarkers in peripheral blood of schizophrenia using bioinformatic methods and machine learning algorithms.

Schizophrenia is a group of severe neurodevelopmental disorders. Identification of peripheral diagnostic biomarkers is an effective approach to improving diagnosis of schizophrenia. In this study, four datasets of schizophrenia patients' blood or serum samples were downloaded from the GEO database and merged and de-batched for the analyses of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WCGNA). The WGCNA analysis showed that the cyan module, among 9 modules, was significantly related to schizophrenia, which subsequently yielded 317 schizophrenia-related key genes by comparing with the DEGs. The enrichment analyses on these key genes indicated a strong correlation with immune-related processes. The CIBERSORT algorithm was adopted to analyze immune cell infiltration, which revealed differences in eosinophils, M0 macrophages, resting mast cells, and gamma delta T cells. Furthermore, by comparing with the immune genes obtained from online databases, 95 immune-related key genes for schizophrenia were screened out. Moreover, machine learning algorithms including Random Forest, LASSO, and SVM-RFE were used to further screen immune-related hub genes of schizophrenia. Finally, CLIC3 was found as an immune-related hub gene of schizophrenia by the three machine learning algorithms. A schizophrenia rat model was established to validate CLIC3 expression and found that CLIC3 levels were reduced in the model rat plasma and brains in a brain-regional dependent manner, but can be reversed by an antipsychotic drug risperidone. In conclusion, using various bioinformatic and biological methods, this study found an immune-related hub gene of schizophrenia - CLIC3 that might be a potential diagnostic biomarker and therapeutic target for schizophrenia.

Heart rate variability as an independent predictor for 8-year mortality among chronic hemodialysis patients.

The repeated measurements of heart rate variability (HRV) is more relevant than a single HRV measurement in predicting patient prognosis but is less addressed previously. This prospective study aimed to investigate the association between repeated measurements of HRV and long-term mortality in chronic hemodialysis patients. The 164 patients (65.0 ± 13.1 years; woman, 57.3%) were enrolled from June 1, 2010, to August 31, 2010, and received four HRV measurements (before and during the index hemodialysis session) after the enrollment. The baseline characteristic and clinical variables, including mortality, were documented. The joint modeling method and Cox regression were used for statistical analyses. After an 8-year follow-up, 79 patients expired, and 85 patients survived. We found that higher normalized high-frequency (nHF) (hazard ratio [HR] 1.033) as well as lower very-low-frequency (HR 0.990), Variance (HR 0.991), normalized low-frequency (HR 0.999, P = 0.006), and low-frequency/high-frequency ratio (HR 0.796) were independent predictors for cardiovascular mortality. Whereas the independent predictors for infection-associated mortality included higher nHF (HR 1.033) as well as higher age (HR 19.29) and lower serum albumin (HR 0.01, P = 0.001). (all P < 0.001 unless otherwise stated) In conclusion, HRV measurement predicts long-term mortality among hemodialysis patients.

Receipt of Vasopressors Is Positively Associated With the Length of the Actively Dying Process in Hospitalization.

BACKGROUND: End-of-life care is important in general hospitalization care. However, the clinical impact of using vasopressors on the length of the actively dying process is still controversial. METHODS: We reviewed patients who were hospitalized in general wards and died before discharge. We classified the patients into 2 groups: those who received vasopressors (RVs) and those who did not receive vasopressors (NRV). We analyzed the factors associated with the length of hospital stay (LOS) and the length of the actively dying process. RESULTS: In all, 745 participants, 10.01% of all admitted patients, were analyzed. Of them, 225 patients were RV group, and the remaining 520 were NRV group. Age and gender were comparable in the 2 groups. The use of vasopressors was associated with an admission diagnosis of sepsis and absence of Do-Not-Resuscitate consent and parenteral use of morphine. In multivariable analysis, a high Barthel index score, the absence of cancer and cardiopulmonary resuscitation (CPR), and no receipt of vasopressors were independent factors for LOS. For the length of the actively dying process, a longer duration of inotropic agent, the receipt of vasopressors, and the absence of CPR were independent factors. CONCLUSION: In-hospital mortality is not uncommon during hospitalization in a general ward. The length of the actively dying process is extended by the use of vasopressors. Further prospective study is required for cautious evaluation of the pros and cons of using vasopressors at the end of life during hospitalization.

Systems pharmacology-based investigation of Sanwei Ganjiang Prescription: related mechanisms in liver injury.

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.

Correction: Heart rate variability during hemodialysis is an indicator for long-term vascular access survival in uremic patients.

[This corrects the article DOI: 10.1371/journal.pone.0172212.].

Heart rate variability during hemodialysis is an indicator for long-term vascular access survival in uremic patients.

BACKGROUND: Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes. METHODS: This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65.1 ± 12.9 years) from June 2010 to August 2010. Each participant received a series of HRV measurements at enrollment. After a 60-month follow-up period, we retrospectively reviewed all events and therapeutic procedures of the VAs which existed at the enrollment and during the follow-up period. RESULTS: During the 60-month follow-up period, 37 (26.8%) had VAF but 138 (73.2%) didn't. The values of most HRV indices were statistically increased during hemodialysis since initiation in the non-VAF group, but not in the VAF group. Among all participants, the independent indicators for VAF included higher normalized high-frequency (nHF) activity [hazard ratio (HR) 1.04, p = 0.005], lower low-frequency/high-frequency (LF/HF) ratio (HR 0.80, p = 0.015), experience of urokinase therapy (HR 11.18, p = 0.002), percutaneous transluminal angioplasty (HR 2.88, p = 0.003) and surgical thrombectomy (HR 2.36, p = 0.035), as well as higher baseline serum creatinine (HR 1.07, p = 0.027) and potassium level (HR 1.58, p = 0.037). In subgroup analysis, a lower sympathetic activity indicated by lower LF/HF ratio was an independent indicator for VAF (HR 0.61, p = 0.03) for tunneled cuffed catheter, but conversely played a protective role against VAF (HR 1.27, p = 0.002) for arteriovenous fistula. CONCLUSIONS: HRV is a useful tool for predicting long-term VAF among hemodialysis patients.

[Criteria suitable for diagnosis of acute respiratory distress syndrome/multiple organ dysfunction syndrome at moderately high altitude area].

OBJECTIVE: To compare the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plain, and to establish a more practical diagnostic criterion of H-ARDS/MODS. METHODS: Five hundred and five cases fulfilled the criteria for the diagnosis of ARDS/MODS were divided into three groups according to the altitude of their habitation: control group including inhabitants (<430 m) on plain (CG, n=113), moderate high altitude group 1 inhabitants at the altitude of 1,517 m (H1G, n=314), moderate high altitude group 2 inhabitants at the altitude of 2,261 m to 2,400 m (H2G, n=78). The ARDS/MODS scores of the three groups were made according to the diagnostic criteria of Lushan conference, Marshall(1995) and Lanzhou criteria drafted by the authors respectively to set up three data analyzing models, followed by plotting of receiver operating characteristic curves (ROC curve) and calculation of the Yordon Index and the optimum cutoff points of the parameters,in order to study the accuracy of the three diagnostic criteria in predicting the outcome of the patients suffering from ARDS/MODS. RESULTS: In CG group, the differences were not significant in area of ROC, the maximal Yordon Index, the optimum cutoff points and the sensitivity and the specificity for three criteria; but the differences were significant for the three criteria in H1G group. Further investigation in comparing the ROC values of lung, brain, heart and kidney, the Lanzhou criteria were more advantageous in the high altitude than the other criteria. CONCLUSION: (1)The current diagnostic criteria of ARDS/MODS are not suitable for the diagnosis of these syndromes in moderately high or high altitude areas. It is necessary to revise the diagnostic criteria of H-ARDS/MODS. (2)One thousand five hundred and seventeen meters in altitude might be considered to be an important borderline, above with the diagnostic criteria of ARDS/MODS for patients inhabiting on plain could not be suitably applied to those living above this level.

[Study of diagnostic criteria of acute respiratory distress syndrome and multiple organ dysfunction syndrome at high altitude: revised draft of the diagnostic criteria of high acute respiratory distress syndrome drawn in Lanzhou conference].

OBJECTIVE: To compare the difference of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plains and reevaluate the practicality and feasibility of the diagnostic criteria of H-ARDS (Lanzhou conference, 1999). METHODS: Three hundred and sixty cases with relatively complete data were divided into three groups according to their originating altitude: control group on plains (CG, n=93), high altitude group 1 at the altitude of 1,517 m (H1G, n=223), high altitude group 2 at the altitude of 2,261-2,400 m (H2G, n=44). The ARDS/MODS scorings of the three groups were carried out according to the diagnostic criteria of Lushan Conference, Marshall (1995) and Lanzhou criteria drafted by the authors and the receiver operating characteristic curves (ROC curve) were made to predict the outcome of MODS. RESULTS: In CG group, the area of ROC, the susceptibility and specificity were 0.823, 0.833, 0.731, respectively according to Lushan criteria, which were better than those (0.815, 0.767, 0.763) according to Marshall criteria. Then in group H2G, the area of ROC, the susceptibility and specificity according to Lushan criteria were lower than those according to Marshall criteria: 0.855, 0.583, 0.969 vs 0.914, 1.000, 0.657. The optimum cutoff points of partial pressure of oxygen in artery (PaO(2))/fractional concentration of inspired oxygen (FiO(2)) were 198.32 mmHg, 131.50 mmHg and 97.58 mmHg in group CG, H1G and H2G. CONCLUSION: (1) There are significant differences between the diagnostic criteria of ARDS at high altitude and that on plains. The altitude of 1 517 m would be an important border line in diagnosing H-ARDS. (2) The drafted diagnostic criteria of ARDS at high altitude are feasible and practical in this region, but the range of the parameters is still wide, which need to be properly amended. (3) The changing tendency of the parameters of MODS at high altitude is different from that on plains, but the amount of sample needs to be accumulated further and the Lanzhou criteria needs to be perfected.

Demand and predictors for post-discharge medical counseling in home care patients: a prospective cohort study.

RATIONALE: Post-discharge care is challenging due to the high rate of adverse events after discharge. However, details regarding post-discharge care requirements remain unclear. Post-discharge medical counseling (PDMC) by telephone service was set-up to investigate its demand and predictors. METHODS: This prospective study was conducted from April 2011 to March 2012 in a tertiary referral center in northern Taiwan. Patients discharged for home care were recruited and educated via telephone hotline counseling when needed. The patient's characteristics and call-in details were recorded, and predictors of PDMC use and worsening by red-flag sign were analyzed. RESULTS: During the study period, 224 patients were enrolled. The PDMC was used 121 times by 65 patients in an average of 8.6 days after discharge. The red-flag sign was noted in 17 PDMC from 16 patients. Of the PDMC used, 50% (n = 60) were for symptom change and the rest were for post-discharge care problems and issues regarding other administrative services. Predictors of PDMC were underlying malignancy and lower Barthel index (BI). On the other hand, lower BI, higher adjusted Charlson co-morbidity index (CCI), and longer length of hospital stay were associated with PDMC and red-flag sign. CONCLUSIONS: Demand for PDMC may be as high as 29% in home care patients within 30 days after discharge. PDMC is needed more by patients with malignancy and lower BI. More focus should also be given to those with lower BI, higher CCI, and longer length of hospital stay, as they more frequently have red flag signs.

Systems pharmacology-based investigation of Sanwei Ganjiang Prescription: related mechanisms in liver injury / 中国天然药物

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.

Systems pharmacology-based investigation of Sanwei Ganjiang Prescription: related mechanisms in liver injury / 中国天然药物

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.

Clinical experience analysis of liver transplantation from donation after citizen’s death in 78 cases / 器官移植

Objective To summarize the clinical experience and effect analysis of liver transplantation from donation after citizen’s death. Methods Clinical data of 76 donors and 78 recipients of liver transplantation from donation after citizen’s death completed in Liver Transplantation Center of West China Hospital,Sichuan University from March 2012 to November 2015 were analyzed retrospectively.The functional recovery of early allografts in liver transplant recipients was observed and the risk factors causing early allograft dysfunction (EAD)were analyzed.In addition,long﹣term survival of allografts and recipient as well as complications was observed. Results The incidence of postoperative EAD was 36%(28 /78)in 78 recipients.High total bilirubin (TB)and long cold ischemia time constituted the risk factors of EAD. Survival rate of the recipients was 92% (72 /78)during perioperation,and 6 cases died,of which 4 cases died of primary graft dysfunction,1 case of upper gastrointestinal hemorrhage and 1 case of pulmonary infection.Postoperative abdominal infection occurred in 5 cases,with biliary stricture in 3 cases and vascular thrombosis in 2 cases.One case died,and the rest were improved after corresponding treatment.The 1﹣year survival rate of the recipients was 84.2% and 2﹣year survival rate was 80% after operation. Conclusions Liver transplantation from donation after citizen’s death realizes favorable short and long﹣term effects,which can be regarded as a good source of donor livers.Important measures such as controlling the preoperative quality of donor liver and shortening the cold ischemia time can improve the clinical effect.