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Background Post-stroke dysphagia (PSD) is a severe complication of stroke. Cerebral small-vessel disease (CSVD) is a major risk factor for stroke and is associated with swallowing difficulties. Accumulating evidence suggests that enlarged perivascular spaces (ePVSs) are a feature of CSVD. We explored whether ePVSs affect swallowing function in patients with acute ischemic stroke.Methods This was a retrospective analysis of 395 patients with acute ischemic stroke who underwent swallowing examination after stroke who had a cerebral MRI at baseline. Swallowing function was ranked based on Functional Oral Intake Scale (FOIS) score, and ePVSs were rated using a 4-level severity score according to the number of ePVSs in the basal ganglia (BG-ePVS).Results Post-stroke dysphagia was detected in 57.4% of the patients and was related to the presence of BG-ePVS. The degree of ePVS was associated with a strong increase in the risk for incident dysphagia, independent of other standard risk factors for dysphagia. A Spearman correlation analysis showed that an increased FOIS score correlated positively with an increase in the BGPS grade.Conclusions: BG-ePVS are associated with swallowing dysfunction in patients with acute ischemic stroke. The larger the number of BG-ePVS, the more severe the post-stroke dysfunction in swallowing. Accordingly, ePVS should be considered a factor in the prediction of PSD.

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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.

Additional file 1: Table S1. Baseline characteristics of AIS patients according to subcategorized group by AF

Additional file 3: Table S3. Multivariate logistic regression analysis of predictive factors for HI and HT in non-AF patients

Additional file 2: Table S2. Baseline characteristics of AIS patients according to the subcategorized groups of HT

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 to HT. In this study, we aimed to explore whether coagulation 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 hours 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 Conclusions: Low PLT, low MPV and high FIB levels were independently associated with HT in non-AF patients. Additionaly, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that coagulation functions at admission may be beneficial for clinicians to recognize patients with high risk of HT at early stage and improve unfavorable long-term outcomes in non-AF patients.

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.

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.

Background: Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, there are 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. Findings: 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. Interpretation: 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. Funding Statement: This work was supported by grants from the Projects of National Natural Science Foundation of China (No.81873799) and the Projects of Provincial Natural Science Foundation of Zhejiang (No. LY19H090013). Declaration of Interests: The authors declare no financial or other conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University.

// Gui-Qian Huang 1, 2, * , Gui-Qi Zhu 1, 3, * , Yan-Long Liu 4, * , Li-Ren Wang 1, 3 , Martin Braddock 5 , Ming-Hua Zheng 1, 6 , Meng-Tao Zhou 7 1 Department of Infection and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 2 Renji School of Wenzhou Medical University, Wenzhou 325000, China 3 School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China 4 College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China 5 Global Medicines Development, AstraZeneca R&D, Alderley Park, United Kingdom 6 Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China 7 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China * Co-first author Correspondence to: Ming-Hua Zheng, e-mail: zhengmh@wmu.edu.cn Meng-Tao Zhou, e-mail: zmt0417@hotmail.com Keywords: neutrophil-to-lymphocyte ratio, hepatocellular carcinoma, curative liver resection, overall survival Received: November 23, 2015 Accepted: December 14, 2015 Published: December 21, 2015 ABSTRACT 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

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.

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).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.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.Combining AFP-CRUT quintiles with MVI may predict significantly improved outcomes and enhance the predictive power for patient responses to therapeutic intervention.

Objective Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP), D-penicillamine (DPM), methotrexate (MTX), or azathioprine (AZP). Since the optimum treatment regimen remains inconclusive, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse event (AE). Methods We searched PubMed, Embase, Scopus and the Cochrane Library for randomized controlled trials until August 2014. We estimated HRs for MOLT and ORs for AE. The sensitivity analysis based on dose of UDCA was also performed. Results The search identified 49 studies involving 12 different treatment regimens and 4182 patients. Although no statistical significance can be found in MOLT, COT plus UDCA was ranked highest for efficacy outcome amongst all the treatment regimes. While for AEs, compared with OBS or UDCA, monotherapy with COC (OR 5.6, P < 0.001; OR 5.89, P < 0.001), CYP (OR 3.24, P < 0.001; OR 3.42, P < 0.001), DPM (OR 8.00, P < 0.001; OR 8.45, P < 0.001) and MTX (OR 5.31, P < 0.001; OR 5.61, P < 0.001) were associated with statistically significant increased risk of AEs. No significant differences were found for other combination regimes. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Consistently, in the sensitivity analysis, results closely resembled our primary analysis. Conclusions COT plus UDCA was the most efficacious among treatment regimens both for MOLT and AEs.

// Jie You 1, * , Wen-Yue Liu 2, * , Gui-Qi Zhu 3, 4 , Ou-Chen Wang 1 , Rui-Min Ma 1 , Gui-Qian Huang 3, 5, * , Ke-Qing Shi 3, 6 , Gui-Long Guo 1 , Martin Braddock 7 , Ming-Hua Zheng 3, 6 1 Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 2 Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 3 Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 4 School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China 5 Renji School of Wenzhou Medical University, Wenzhou, China 6 Institute of Hepatology, Wenzhou Medical University, Wenzhou, China 7 Global Medicines Development, AstraZeneca R&D, Alderley Park, United Kingdom * These authors have contributed equally to this work Correspondence to: Ming-Hua Zheng, e-mail: zhengmh@wmu.edu.cn Ou-Chen Wang, e-mail: woc099@163.com Keywords: non-metastatic colorectal cancer, metabolic syndrome, overall survival, disease-free survival, risk factor Received: March 27, 2015 Accepted: June 01, 2015 Published: June 12, 2015 ABSTRACT 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.

Supplemental Digital Content is available in the text, 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.

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 β-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.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.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.

BACKGROUND AND AIMS There is no prognostic model that is reliable and practical for patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). This study aimed to establish and validate a Surgery-Specific Cancer of the Liver Italian Program (SSCLIP) scoring system for those patients. METHODS 668 eligible patients who underwent CLR for HCC from five separate tertiary hospitals were selected. The SSCLIP was constructed from a training cohort by adding independent predictors that were identified by Cox proportional hazards regression analyses to the original Cancer of the Liver Italian Program (CLIP). The prognostic performance of the SSCLIP at 12 and 36-months was compared with data from existing models. The patient survival distributions at different risk levels of the SSCLIP were also assessed. RESULTS Four independent predictors were added to construct the SSCLIP, including age (HR = 1.075, 95%CI: 1.019-1.135, P = 0.009), albumin (HR = 0.804, 95%CI: 0.681-0.950, P = 0.011), prothrombin time activity (HR = 0.856, 95%CI: 0.751-0.975, P = 0.020) and microvascular invasion (HR = 19.852, 95%CI: 2.203-178.917, P = 0.008). In both training and validation cohorts, 12-month and 36-month prognostic performance of the SSCLIP were significantly better than those of the original CLIP, model of end-stage liver disease-based CLIP, Okuda and Child-Turcotte-Pugh score (all P < 0.05). The stratification of risk levels of the SSCLIP showed an enhanced ability to differentiate patients with different outcomes. CONCLUSIONS A novel SSCLIP to predict survival of HCC patients who received CLR based on objective parameters may provide a refined, useful prognosis algorithm.

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 ± 25.3 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.