Hemostasis functions are associated with hemorrhagic transformation in non-atrial fibrillation patients: a case-control study.

BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.

The Association Between Admission Anemia and Poststroke Depression.

ABSTRACT: Poststroke depression (PSD) is the most frequent and important neuropsychiatric problem afflicting these patients. Anemia is common in many of these individuals presenting with acute stroke. This study determined whether there is a relationship between anemia on hospital admission and PSD. Two hundred eighty-four acute stroke patients were included in the study. Among them, there were 88 PSD patients, whereas another 196 were non-PSD patients. Clinical depression symptoms were diagnosed according to DSM-4 (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria and a HAMD-17 (the 17-item Hamilton Depression Scale) score ≥8 at 1 month after stroke. In the PSD patients, 27.3% of them presented with anemia, whereas only 12.8% of the non-PSD patients had this condition. There was a negative correlation between hemoglobin level and HAMD-17 score in all patients. A binary logistic regression analysis revealed that anemia was independently associated with PSD after adjustment for sex, National Institutes of Health Stroke Scale scores, mRS (modified Rankin Scale) scores, BI (Barthel Index) scores, RBC (red blood cell), and hematocrit. In conclusion, anemia at admission is associated with PSD seen in these patients 1 month later. Therefore, anemia is a possible predictor of PSD.

Individualized predictions of early isolated distal deep vein thrombosis in patients with acute ischemic stroke: a retrospective study.

BACKGROUND: Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients. METHODS: This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots. RESULTS: The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742-0.806) and 0.820 (95% CI: 0.762-0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT. CONCLUSIONS: The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.

Predictive Value of Nutritional Risk for All-Cause Death and Functional Outcomes in Chinese Elderly Patients with Acute Stroke: A 3-Year Follow-Up Study.

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.

Cascading Photoelectric Detecting and Chemiresistive Gas-Sensing Properties of Pb5 S2 I6 Nanowire Mesh for Multi-Factor Accurate Fire Alarm.

Accurate fire warning is very important for people's life and property safety. The most commonly used fire alarm is based on the detection of a single factor of gases, smoke particles, or temperature, which easily causes false alarm due to complex environmental conditions. A facile multi-factor route for fabricating an accurate analog fire alarm using a Pb5 S2 I6 nanowire mesh based on its photoelectric and gas-sensing dual function is presented. The Pb5 S2 I6 nanowire mesh presents excellent photoelectric detection capabilities and is sensitive to ppm-level NO2 at room temperature. Under the "two-step verification" circuit of light and gas factors, the bimodal simulation fire alarm based on this Pb5 S2 I6 nanowire mesh can resist the interference of complex environmental factors and effectively reduce the false alarm rate.

Association Between Obesity and Post-stroke Anxiety in Patients With Acute Ischemic Stroke.

Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01-1.08) and 1.93 (95% CI: 1.11-3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99-1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80-2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.

Liver Fibrosis Is Associated With Hemorrhagic Transformation in Patients With Acute Ischemic Stroke.

Background: Hemorrhagic transformation (HT) is a frequent, often asymptomatic event that occurs after acute ischemic stroke (AIS). Liver fibrosis, usually subclinical, is common and crucial in the development of liver disease. We aimed to investigate the association between liver fibrosis and HT in patients with AIS. Methods: We performed a single-center and retrospective study. A total of 185 consecutive participants with HT and 199 age- and sex-matched stroke patients without HT were enrolled in this study. We calculated one validated fibrosis index-Fibrosis-4 (FIB-4) score-to assess the extent of liver fibrosis. HT was detected by routine CT or MRI and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. HT was also classified into asymptomatic or symptomatic. We used logistic regression models adjusted for previously established risk factors to assess the risks for HT. Results: The median FIB-4 score was significantly higher among patients who developed HT than among those without HT, whereas standard hepatic assays were largely normal. Patients were assigned to groups of high FIB-4 score and low FIB-4 score based on the optimal cutoff value. Compared with the subjects in the low-FIB-4-score group, incidence of HT for the high-FIB-4-score group was significantly higher. After adjustment for potential confounders, the patients with high FIB-4 score had 3.461-fold risk of HT in AIS compared to the patients with low FIB-4 score [odds ratio, 3.461 (95% CI, 1.404-8.531)]. Conclusion: Liver fibrosis, measured by FIB-4 score, was independently associated with the risk of HT in AIS patients.

High Monocyte-To-Lymphocyte Ratio Is Associated With Stroke-Associated Pneumonia.

Purpose: Stroke-associated pneumonia (SAP), a common complication in acute ischemic stroke (AIS) patients, is associated with poor prognosis after AIS. Inflammation plays an important role in the development of SAP. In this study, we aimed to explore the association between the monocyte-to-lymphocyte ratio (MLR) and SAP in AIS patients. Methods: We continuously enrolled 972 AIS patients. SAP was diagnosed by two trained neurologists and confirmed by radiography, meeting the modified Centers for Disease Control and Prevention criteria. MLR values were measured for all participants, and all patients were evenly classified into three tertiles according to the MLR levels. We used the values that Youden's index max points corresponded to represent the optimal cutoffs, which represented the balance in sensitivity and specificity. Results: 104 (10.7%) patients were diagnosed with SAP. SAP patients showed a significant increased (P < 0.001) MLR when compared with non-SAP. The optimal cutoff points of MLR were (T1) <0.2513, (T2) 0.2513-0.3843, and (T3) > 0.3843. The incidence of SAP was significantly higher in the third MLR tertile than the first and second MLR tertiles (21.7 vs. 4 vs. 6.5%, respectively, P < 0.001). After adjusting for confounding and risk factors, multivariate regression analysis showed that the third MLR tertile was an independent variable predicting the occurrence of SAP (odds ratio = 3.503, 95%CI = 1.066-11.515, P = 0.039). Conclusions: Our study showed that higher MLR was significantly associated with SAP in AIS patients. MLR is beneficial for clinicians to recognize patients with a high risk of SAP at an early stage and is an effective way to improve clinical care of SAP patients. Higher MLR could be a helpful and valid biomarker for predicting SAP in clinical practice.

Individualized Prediction Of Stroke-Associated Pneumonia For Patients With Acute Ischemic Stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) is a serious and common complication in stroke patients. PURPOSE: We aimed to develop and validate an easy-to-use model for predicting the risk of SAP in acute ischemic stroke (AIS) patients. PATIENTS AND METHODS: The nomogram was established by univariate and multivariate binary logistic analyses in a training cohort of 643 AIS patients. The prediction performance was determined based on the receiver operating characteristic curve (ROC) and calibration plots in a validation cohort (N=340). Individualized clinical decision-making was conducted by weighing the net benefit in each AIS patient by decision curve analysis (DCA). RESULTS: Seven predictors, including age, NIHSS score on admission, atrial fibrillation, nasogastric tube intervention, mechanical ventilation, fibrinogen, and leukocyte count were incorporated to construct the nomogram model. The nomogram showed good predictive performance in ROC analysis [AUROC of 0.845 (95% CI: 0.814-0.872) in training cohort, and 0.897 (95% CI: 0.860-0.927) in validation cohort], and was superior to the A2DS2, ISAN, and PANTHERIS scores. Furthermore, the calibration plots showed good agreement between actual and nomogram-predicted SAP probabilities, in both training and validation cohorts. The DCA confirmed that the SAP nomogram was clinically useful. CONCLUSION: Our nomogram may provide clinicians with a simple and reliable tool for predicting SAP based on routinely available data. It may also assist clinicians with respect to individualized treatment decision-making for patients differing in risk level.

Low triiodothyronine syndrome is associated with hemorrhagic transformation in patients with acute ischaemic stroke.

Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. We explored the association between low triiodothyronine (T3) syndrome and HT in AIS patients. A total of 208 consecutive participants with HT and 208 age- and sex-matched stroke patients without HT were enrolled in this study. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction (HI) type 1 or 2 or parenchymal hematoma (PH) type 1 or 2. HT was also classified into asymptomatic or symptomatic. The incidence of low T3 syndrome was significantly higher among patients who developed HT than among those without HT. Moreover, the more severe the HT, the lower the detected T3 levels. Multivariate-adjusted binary logistic regression showed that low T3 syndrome was an independent risk factor for HT and symptomatic HT in AIS patients. Low T3 syndrome was also significantly associated with a higher risk of PH, but not with the risk of HI. Thus, low T3 syndrome was independently associated with the risk of HT, symptomatic HT, and severe HT (PH) in AIS patients, which suggests monitoring T3 could be a useful means of preventing HT in patients with ischemic stroke.

Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.

BACKGROUND AND AIM: Stroke-associated pneumonia (SAP) is a common complication in patients with acute ischemic stroke (AIS). This study explored the potential relationship between serum vitamin D levels and SAP. METHODS: This study recruited 863 consecutive AIS patients. In-hospital SAP was defined as a complication that occurred after stroke, during hospitalization, that was confirmed radiographically. Serum vitamin D levels were measured within 24 hrs of admission and the patients were divided into vitamin D sufficient (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L) groups. RESULTS: In this study, 102 (11.8%) patients were diagnosed with SAP. Compared to the patients without SAP, patients with SAP had significantly lower vitamin D levels (P = 0.023). The incidence of SAP was significantly higher in patients with vitamin D deficiency than in those with vitamin D insufficiency or sufficiency (21.2% vs 16.2% & 9.5%, P = 0.006). After adjusting for confounders, vitamin D deficiency and insufficiency were independently associated with SAP (OR = 3.034, 95% CI = 1.207-7.625, P = 0.018; OR = 1.921, 95% CI = 1.204-3.066, P = 0.006, respectively). In multiple-adjusted spline regression, vitamin D levels showed a linear association with the risk of SAP (P < 0.001 for linearity). CONCLUSION: Reduced vitamin D is a potential risk factor of in-hospital SAP, which can help clinicians identify high-risk SAP patients.

Stratified alpha-fetoprotein pattern accurately predicts mortality in patients with acute-on-chronic hepatitis B liver failure.

BACKGROUND: Alpha-fetoprotein (AFP) has been shown to predict the prognosis of liver disease in several studies. This study aimed to evaluate the prognostic value of stratified AFP in patients with acute-on-chronic hepatitis B liver failure (ACHBLF). METHODS: A total of 192 patients were included and AFP were categorized into quartiles. The prognostic value was determined for overall survival (OS) and assessed by Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses studied the association of all independent parameters with disease prognosis. RESULTS: The optimal cut-off points of AFP were: (Q1) 252.3-4800.0 ng/ml, (Q2) 76.0-252.2 ng/ml, (Q3) 18.6-75.9 ng/ml, and (Q4) 0.7-18.5 ng/ml. Based on the Kaplan-Meier analysis of the OS, each AFP quartile revealed a progressively worse OS and apparent separation (log-rank P = 0.006). The second-highest quartiles of AFP (Q2) always demonstrated an extremely favorable short-term survival. Combining the lowest AFP quartiles with a serum sodium < 131mmol/L or an INR ≥ 3.3 showed a poor outcome (90-days survival of 25.0% and 11.9% respectively). CONCLUSIONS: Stratified AFP could strengthen the predictive power for short-term survival of patients with ACHBLF. Combining AFP quartiles with low serum sodium and high INR may better predict poor outcome in ACHBLF patients.

Stratified Platelet-to-lymphocyte Ratio: A Novel Target for Prognostic Prediction of Hepatocellular Carcinoma after Curative Liver Resection.

Background and Aims: Platelet-to-lymphocyte ratio (PLR) has been shown to predict prognosis of cancers. We aimed to evaluate the prognostic value of stratification of PLR in patients after curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods: A total of 1804 patients who underwent CLR for suspected HCC between January 2007 and January 2014 were screened for the study. All of the patients were categorized into equal tertiles according to the number of patients and the distribution of PLR. Prognostic significance was determined for overall survival (OS) and was assessed using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis. Results: The optimal cut-off points of preoperative PLR were: (T1) 11.98-75.00, (T2) 75.00-113.33 and (T3) 113.33-567.50. There were obvious differences in each PLR tertile with mortality within 36 months of CLR (plog-rank < 0.001). Multivariable analysis suggested that the level of PLR (HR = 1.004, 95%CI: 1.001-1.008, p = 0.006), portal vein thrombosis (HR = 3.406, 95%CI: 1.185-9.794, p = 0.023), number of nodules (HR = 1.810, 95%CI: 1.345-2.437, p < 0.001), Child-Turcotte-Pugh score (HR = 1.741, 95%CI: 1.129-2.684, p = 0.012) and microvascular invasion (HR = 2.730, 95%CI: 1.777-4.196, p < 0.001) were significant predictors of mortality. Kaplan-Meier analysis of overall survival (OS) demonstrated that each PLR tertile showed a progressively worse OS and apparent separation (plog-rank = 0.016). The highest 5-year OS rate following CLR (58%) was revealed in tertile 1. In contrast, the lowest 5-year OS rate (30%) was revealed in tertile 3. Conclusion: Stratified preoperative PLR could strengthen the predictive power for OS in HCC patients with CLR.

Stratified neutrophil-to-lymphocyte ratio accurately predict mortality risk in hepatocellular carcinoma patients following curative liver resection.

OBJECTIVES: Neutrophil lymphocyte ratio (NLR) has been shown to predict prognosis of cancers in several studies. This study was designed to evaluate the impact of stratified NLR in patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). METHODS: A total of 1659 patients who underwent CLR for suspected HCC between 2007 and 2014 were reviewed. The preoperative NLR was categorized into quartiles based on the quantity of the study population and the distribution of NLR. Hazard ratios (HRs) and 95% confidence intervals (CIs) were significantly associated with overall survival (OS) and derived by Cox proportional hazard regression analyses. Univariate and multivariate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis. RESULTS: Multivariable Cox proportional hazards models showed that the level of NLR (HR = 1.031, 95%CI: 1.002-1.060, P = 0.033), number of nodules (HR = 1.679, 95%CI: 1.285-2.194, P<0.001), portal vein thrombosis (HR = 4.329, 95%CI: 1.968-9.521, P<0.001), microvascular invasion (HR = 2.527, 95%CI: 1.726-3.700, P<0.001) and CTP score (HR = 1.675, 95%CI: 1.153-2.433, P = 0.007) were significant predictors of mortality. From the Kaplan-Meier analysis of overall survival (OS), each NLR quartile showed a progressively worse OS and apparent separation (log-rank P=0.008). The highest 5-year OS rate following CLR (60%) in HCC patients was observed in quartile 1. In contrast, the lowest 5-year OS rate (27%) was obtained in quartile 4. CONCLUSIONS: Stratified NLR may predict significantly improved outcomes and strengthen the predictive power for patient responses to therapeutic intervention.

A network meta-analysis of the efficacy and side effects of UDCA-based therapies for primary sclerosing cholangitis.

OBJECTIVES: Therapies for treatment of patients with primary sclerosing cholangitis (PSC) include administration of ursodeoxycholic acid (UDCA) alone, or combination with metronidazole (MTZ) or mycophenolate mofetil (MMF), respectively. However, the optimum regimen still remains inconclusive. We aimed to compare interventions in terms of patient mortality or liver transplantation (MOLT), progression of liver histological stage (POLHS), serum bilirubin, alkaline phosphatase (ALP) levels and adverse events (AE). METHODS: We searched PubMed, Embase and the Cochrane Library for randomized controlled trials until 31, Jan 2015. We estimated hazard ratios (HRs), odds ratios (ORs) and mean difference (MD) between treatments on clinical outcomes. Sensitivity analyses based on the dose of UDCA, quality of trials or treatment duration were also performed. RESULTS: Ten RCTs were included. Compared with UDCA plus MTZ, UDCA (HR 0.28, 95%CI 0.01-3.41), UDCA plus MMF (HR 0.08, 95%CI 0.00-4.18), or OBS (HR 0.28, 95%CI 0.01-3.98) all provided an increased risk of MOLT. UDCA provided a significant reduction in bilirubin and ALP levels compared with OBS (MD -13.92, P < 0.001; MD -484.34, P < 0.001; respectively). With respect to POLHS, although differing not significantly, UDCA plus MTZ had a tendency to improve LHS more than UDCA (OR 1.33), UDCA plus MMF (OR 3.24) or OBS (OR 1.08). Additionally, UDCA plus MTZ (MD -544.66, P < 0.001) showed a significant reduction in ALP levels compared with OBS, but appeared to be associated with more AEs compared with UDCA (OR 5.09), UDCA plus MMF (OR 4.80) or OBS (OR 7.21). CONCLUSIONS: MTZ plus UDCA was the most effective therapy in survival rates and liver histological progression.

Combined AFP-CRUT with microvascular invasion accurately predicts mortality risk in patients with hepatocellular carcinoma following curative liver resection.

AIMS: To establish and validate an equation of α-fetoprotein (AFP) change rate over unit time (AFP-CRUT) as a potential predictor of survival after resection in patients with hepatocellular carcinoma (HCC). METHODS: The AFP-CRUT was constructed based on dynamic variation in AFP over time and then categorized into quintiles. The area under the receiver operating characteristic (ROC) curve showed the performance for survival prediction. RESULTS: As independent risk factors associated with mortality, microvascular invasion (MVI) (p = 0.003) and AFP-CRUT quintiles (p = 0.048) were combined to enhance the predictive effect. The highest 5-year overall survival rate following curative liver resection (93%) was observed in patients with MVI absent and AFP-CRUT in quintile 1 (49.64 to 209.61). In contrast, the lowest 5-year overall survival (7%) was obtained in quintile 5 (-469.29 to 6.45) with MVI present. In validation cohorts at both 12 and 24 months, AFP-CRUT performed well as a potential prognostic biomarker. CONCLUSIONS: Combining AFP-CRUT quintiles with MVI may predict significantly improved outcomes and enhance the predictive power for patient responses to therapeutic intervention.

Network meta-analysis of randomized controlled trials: efficacy and safety of UDCA-based therapies in primary biliary cirrhosis.

Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09-1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02-4.83), COC plus UDCA (HR 0.39, 95% CI 0.07-2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05-1.63), or OBS (HR 0.49, 95% CI 0.11-2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59-20.67), COT plus UDCA (OR 2.27, 95% CI 0.15-33.36), COC plus UDCA (OR 1.00, 95% CI 0.09-12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23-17.82), or OBS (OR 3.00, 95% CI 0.53-20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.

Metabolic syndrome contributes to an increased recurrence risk of non-metastatic colorectal cancer.

OBJECTIVES: Epidemiological data suggests a close link between metabolic syndrome (MetS) and non-metastatic colorectal cancer (NMCRC). However, the relationship between MetS and the outcome of NMCRC is less well understood. We aim to evaluate the impact of MetS on the prognosis in NMCRC patients. METHODS: We performed a large cohort study of 1069 NMCRC patients. The Kaplan-Meier method was used to calculate the cumulative survival rate. Cox proportional hazard regression models were used to analyze the prognosis associated with MetS adjusting for clinicopathologic variables. RESULTS: MetS was identified in 20.7% of NMCRC patients. Patients with MetS were more likely to be older, higher levels of blood glucose, triglycerides, high density lipoprotein, and uric acid than patients without MS (P < 0.05 for all). During a mean period of 59.6 months follow-up, patients with MetS had a statistically significantly lower rate of disease-free survival (DFS) than the patients without MetS (P = 0.014), especially local recurrence (P = 0.040). However, there was no difference in overall survival (P = 0.116). Multivariate analysis showed that the presence of MetS was an independent risk factor for DFS (HR = 0.733, 95%CI 0.545-0.987, P = 0.041), but not for OS (P = 0.118). CONCLUSIONS: MetS is associated with an increased recurrence risk of NMCRC.

Targeting fibroblast growth factor 19 in liver disease: a potential biomarker and therapeutic target.

INTRODUCTION: Fibroblast growth factor 19 (FGF19) is a member of the hormone-like FGF family and has activity as an ileum-derived postprandial hormone. It shares high binding affinity with ß-Klotho and together with the FGF receptor (FGFR) 4, is predominantly targeted to the liver. The main function of FGF19 in metabolism is the negative control of bile acid synthesis, promotion of glycogen synthesis, lipid metabolism and protein synthesis. AREAS COVERED: Drawing on in vitro and in vivo studies, this review discusses FGF19 and some underlying mechanisms of action of FGF19 as an endocrine hormone in several liver diseases. The molecular pathway of the FGF19-FGFR4 axis in non-alcoholic liver disease and hepatocellular carcinoma are discussed. Furthermore, definition of function and pharmacological effects of FGF19 for liver disease are also presented. EXPERT OPINION: A series of studies have highlighted a crucial role of FGF19 in liver disease. However, the conclusions of these studies are partly paradoxical and controversial. An understanding of the underlying biological mechanisms which may explain inconsistent findings is especially important for consideration of potential biomarker strategies and an exploration of the putative therapeutic efficacy of FGF19 for human liver disease.

Nonalcoholic fatty liver disease: a negative risk factor for colorectal cancer prognosis.

Nonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD. We performed a large cohort study of 1314 patients who were first diagnosed with CRC between January 2006 and April 2011. Postoperative follow-up data were collected from out-patient medical records, telephone consultations, and social security death indices. The Kaplan-Meier method was used to calculate the cumulative survival rate. Clinicopathologic variables were analyzed by univariate analysis and multivariate analysis through a Cox proportional hazard regression model. The mean follow-up time was 52.7 ±â€Š25.3 months. Upon baseline comparison, the NAFLD group had significantly higher values of body mass index, triglycerides, and uric acid and significantly lower values of high-density lipoprotein, compared with the non-NAFLD group (P < 0.05 for all). There were no significant differences between the 2 groups with regard to tumor location, TNM staging, tumor differentiation, carcinoembryonic antigen, and vascular invasion. The cumulative 1-, 3-, and 5-year OS rates were 96.1%, 85.2%, and 80.6%, respectively, in the NAFLD group, which were statistically significantly higher than the OS rates of 91.6%, 76.2%, and 67.8%, respectively, in the non-NAFLD group (P = 0.075, P = 0.002, P = 0.030, respectively). There was no difference in DFS rates between the CRC patients with and without NAFLD (P = 0.267). Multivariate analysis showed that the presence of NAFLD was an independent negative risk factor for OS after adjusting for clinicopathologic covariates (hazard ratio = 0.593; 95% confidence interval 0.442, 0.921; P = 0.020), but not for DFS (P = 0.270). NAFLD may play a protective role in OS for CRC patients. Further studies are needed to elucidate the molecular mechanisms of putative protective effects in CRC patients with NAFLD.