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In clinical trials of systemic therapy for advanced hepatocellular carcinoma (HCC), Asian trials almost always reported poorer survival than non-Asian trials. This study sought to identify contributory factors for this geographic difference. A systematic review was done on randomized trials for unresectable HCC that used systemic therapy as an experimental arm and placebo or supportive care as control. Meta-analysis was performed with the consideration of fixed and random effects. Then, meta-regression was performed to identify predictors of patient survival in the control arm and the treatment effects (improvement in median survival). Fourteen trials (6 Asians, 8 non-Asians) were eligible for meta-analysis. The median survival of patients in the control arm, which indicated natural history of advanced HCC patients, was 3.57 ± 1.88 months in Asian trials and 5.96 ± 1.46 months in non-Asian trials ( p = 0.02). Independent predictors of better survival included non-Asian trials ( p = 0.0007), higher percentage of Child A cirrhosis ( p = 0.01) and hepatitis B (HBV)-related HCC ( p = 0.02). Sub-group analysis suggested that Asian trials tended to enroll patients with more advanced diseases. Independent predictors of better treatment effect included non-Asian trials, higher percentage of extra-hepatic metastasis, HBV-related HCC, and poorer trial quality. The quantitative estimation of the geographic difference can help design of future clinical trials of advanced HCC.

This study investigated the functional performance of daily activities at home and at school in a population-based sample of children with different degrees of motor coordination impairment and competence. Sixteen children (seven males, nine females; mean age 8 y, SD 9 mo) with developmental coordination disorder (DCD), 25 with suspected DCD ([sDCD] 17 males, eight females; mean age 7 y 6 mo, SD 8 mo), and 63 children without motor problems (39 males, 24 females; mean age 7 y 9 mo, SD 7 mo) were recruited from public schools (Grades 1-3, age 6 y 4 mo-9 y 10 mo) using the Chinese version of the Developmental Coordination Disorder Questionnaire, the Movement Assessment Battery for Children, and the Bruininks-Oseretsky Test of Motor Proficiency. Functional performance was assessed using the Chinese versions of the Vineland Adaptive Behavior Scales and the School Function Assessment-Chinese version. The functional performance of children with DCD and sDCD was statistically significantly lower than those without DCD (p's0.05). chi(2) and logistic regression analyses showed significant differences among all groups in the proportion of children scoring at the 'inadequate' adaptive level of home performance (p's0.05). There were also significant differences among the groups in the proportion of children scoring below the cut-off in school performance (p's0.05). The findings show the pervasive impact of DCD on children's functional performance in daily activities at home and at school.

Background Fluoroquinolones are frequently used to replace agents in first-line anti-tuberculosis (anti-TB) regimens in patients with TB who have drug-induced hepatic dysfunction. We investigated the safety of using fluoroquinolone in an area where TB is endemic and where there is a high incidence of drug-induced liver injury. Methods From September 2003 through August 2006, patients who had aspartate aminotransferase and/or alanine aminotransferase levels >3 times the upper limit of normal in the presence of hepatitis symptoms or who had aspartate aminotransferase and/or alanine aminotransferase levels >5 times the upper limit of normal after receipt of anti-TB treatment were enrolled. The control group received ethambutol, with or without streptomycin; study groups received either (1) ethambutol plus levofloxacin, with or without streptomycin; or (2) ethambutol plus moxifloxacin, with or without streptomycin. The outcome measurement was the time from onset of hepatitis to normalization of liver functions. Results One hundred thirty-four (11.3%) of 1191 patients received a diagnosis of hepatotoxicity and needed to stop anti-TB treatment. The risk factor was abnormal baseline transaminase levels. Twenty-two of the 134 patients received the control medication, 40 received levofloxacin, and 45 received moxifloxacin; the remaining patients were excluded from the study. There were no significant prestudy differences between groups. Time to liver function normalization was almost the same for all groups (mean +/- standard deviation, 29.1+/-21.4, 25.5+/-17.6, and 29.7+/-14.3 days, respectively). Conclusions Abnormal baseline transaminase levels are the independent risk factors for anti-TB therapy-induced hepatitis. Levofloxacin and moxifloxacin caused no additional hepatotoxicity when they were used by patients with hepatitis induced by first-line anti-TB drugs.

Residual renal function (RRF) at the initiation of peritoneal dialysis (PD) therapy can predict patient outcome. However, RRF declines with time at variable rates in different patients. This study was performed to compare the impact of baseline RRF and the rate of RRF decline on patient survival and on death-censored technique survival after initiation of long-term PD.We enrolled 270 patients with sufficient urine amount (daily urine volume100 mL) from a medical centre in North Taiwan who began PD between January 1996 and December 2005 and followed them until December 2007. The study population was stratified by the decline rate of RRF into a fast, intermediate and slow decline group. The Kaplan-Meier survival analysis was used to determine patient survival and technique survival. The Cox regression model was used to identify factors associated with patient outcome. The proportional odds polychotomous logistic regression model was used to identify variables associated with rapid decline of RRF.During an average follow-up period of 45 months, 50 (18.5%) deaths, 67 (24.8%) death-censored technique failures (transfer to haemodialysis) and 43 (15.9%) renal transplantations occurred. The median rate of RRF decline was 0.885 mL/min/1.73 m(2) per year. Survival analysis showed that patients with fast RRF decline had worse survival and increased risk of technique failure. The multivariate Cox regression model confirmed that the rate of RRF decline was an independent factor associated with patient and technique survival and was a more powerful prognostic factor than basal RRF. Variables associated with a rapid decline of RRF were larger body mass index, presence of diabetes, prior history of congestive heart failure, use of diuretics, peritonitis episodes and hypotensive events.Our data indicate that the rate of decline of RRF is a more powerful prognostic factor than baseline RRF associated with all-cause mortality and technique failure in patients on long-term PD. To prevent accelerated loss of RRF, it is imperative that every effort be made to avoid overdiuresis, peritonitis and hypotensive episodes, especially in those with diabetes, obesity and congestive heart failure.

Mitosis dysregulation is common in cancers. This study explored the nuclear expression patterns and prognostic significance of mitotic regulatory proteins, including Aurora kinases, survivin, and p53, in biliary tract cancer (BTC). Archival tumor samples from 161 BTC patients who underwent surgery were tested for the expression of Aurora-A, Aurora-B, survivin, and p53 by immunohistochemistry. The potential endogeneity among the clinicopathologic variables and survival outcome was assessed by a generalized simultaneous equations model. Nuclear overexpression of Aurora-A, Aurora-B, survivin, and p53 was found in 79 (49.1%), 45 (28.0%), 55 (34.2%), and 55 (34.2%) patients, respectively. Intrahepatic cholangiocarcinoma, compared with the other two subtypes, had significantly higher proportions of nuclear overexpression of Aurora-B and survivin (37.8% and 47.3%, respectively). Simultaneous overexpression of Aurora-A and Aurora-B was correlated with that of p53. Overexpression of Aurora-B was also correlated with that of survivin and tumor grade. Our data indicate that simultaneous overexpression of Aurora-A and Aurora-B, suggesting dysregulated mitosis is associated with worse survival in patients with BTC. Independent prognostic factors for poor overall survival included simultaneous overexpression of Aurora-A and Aurora-B (hazard ratio, 1.997; 95% confidence interval, 1.239-3.219; P = 0.0045) and tumor grade (hazard ratio, 2.117; 95% confidence interval, 1.339-3.348; P = 0.0013) assessed by a multivariate analysis stratified by American Joint Committee on Cancer stage and p53 overexpression. Endogeneity testing suggested that nuclear overexpression of p53 and tumor type may influence patient survival through their interactions with Aurora-A/Aurora-B expression and tumor grade. (Cancer Epidemiol Biomarkers Prev 2009;18(2):417–23)

Objectives To investigate the expression of stathmin in upper urinary tract (UUT) urothelial carcinoma (UC) in human tissues and to determine whether the level of stathmin expression was correlated with prognosis because overexpression of stathmin has been observed in various malignancies. Methods We first analyzed stathmin mRNA level in 5 UUT-UC paired fresh specimens (tumor and nontumoral urothelium) by RT-PCR. Besides, a total of 58 patients with localized UUT-UC (pT1-3N0M0) treated by nephroureterectomy were enrolled. The stathmin expression in UUT-UC specimens was analyzed by immunohistochemical (IHC) staining. Stathmin IHC score was defined as the proportion of positive staining tumor cells from each patient's specimen. The stathmin IHC score ≥ 0.5 was defined as strong (+) immunoreactivity and Results Significant differences in stathmin mRNA between UUT-UC and paired normal urothelium were noted in 5 of the patients. Of the 58 UUT-UC specimens, stathmin immunoreactivity (strong [+] vs weak [−]) was significantly associated with pT stage ( P = .006) as well as with recurrence-free and cancer-specific survival. In multivariate analysis, stathmin IHC score was a significant predictor for both recurrence-free survival (hazard rates: 22.4; P = .001) and cancer-specific survival (hazard rates: 39.8; P = .0012). Conclusions The stathmin immunostaining is a novel prognosticator for patients with localized UUT-UC stathmin may be a help identify such patients with poor outcomes to benefit from receiving close follow-up and early adjuvant therapy.

Objectives To examine the psychometric properties of the Chinese version of Swanson, Nolan and Pelham IV Scale (SNAP-IV)-Teacher Form. Methods The sample included a representative sample of 3,653 first to eighth graders (boys, 52.3%) and 190 children diagnosed with ADHD (aged 6–15). Teachers completed the Chinese versions of the SNAP-IV, and Strengths and Difficulties Questionnaire. Results The confirmatory factor analysis revealed a four-factor structure (inattention, hyperactivity, impulsivity, and opposition) with an adequate fit (Comparative Fit Index ¼0.990; root mean square error of approximation ¼0.058). The test–retest reliability (intraclass correlations ¼0.60–0.84), internal consistency (a ¼.88–.95), and concurrent validity (Pearson correlations ¼0.61–0.84) were satisfactory. Children with both ADHD and oppositional defiant/ conduct disorders had the highest scores, followed by children with ADHD only who had intermediate scores and then school-based participants who had the lowest scores. Conclusions Our findings suggest that the Chinese SNAP-IV-Teacher Form is a reliable and valid instrument for rating ADHD and oppositional symptoms (ClinicalTrials.gov number, NCT00491361).

The aim of this study was to compare six prognostic staging systems (Okuda stage, TNM stage, CLIP score, BCLC stage, JIS score and Tokyo score) in predicting survival in patients with hepatocellular carcinoma (HCC). A total of 2010 Taiwanese HCC patients were included. Demographic, laboratory and tumour characteristics were determined at diagnosis. Predictors of survival included serum levels of albumin, total bilirubin, alkaline phosphatase, alpha-fetoprotein, ascites, tumour size and portal vein invasion. The Tokyo score was the most informative one for predicting the survival of HCC patients as a whole, receiving surgical resection, or receiving transarterial chemoembolisation. CLIP score was the best fit system for HCC patients receiving chemotherapy or supportive care. Each staging system showed a significant difference in predicting the probability of survival across different stages. The applicability of staging systems for patients with HCC was dependent on treatment methods.

Background In postsurgical acute renal failure patients with moderate unstable hemodynamics or fluid overload, the choice of dialysis modality is difficult. This study was performed to compare the outcomes between the sustained low-efficiency dialysis (SLED) and continuous veno-venous hemofiltration (CVVH) in these patients. Methods Sequential postsurgical acute renal failure patients undergoing acute dialysis with CVVH (2002–2003), or SLED (2004–2005) as a result of severe fluid overload or moderately unstable hemodynamics were analyzed. Multivariate analyses of comorbidity, disease severity before initiating dialysis, biochemical measurements, and hemodynamic parameters for 3 days after the first dialysis session were performed by fitting multiple logistic regression models to predict patient's 30-day after hospital discharge (AHD) mortality. Results Among the 101 recruited patients, 38 received SLED and the rest received CVVH. The 30-day AHD mortality was 62.4%. The independent risk factors of 30-day AHD mortality included older age (P = .008), lower first postdialysis mean arterial pressure (MAP) (P = .021), higher first postdialysis blood urea nitrogen level (P = .009), and absence of a history of hypertension (P = .002). A further linear regression analysis found that dialysis using SLED was associated with higher first postdialysis MAP (P = .003). Conclusions Among the postsurgical patients requiring acute dialysis with severe fluid overload or moderately unstable hemodynamics, the patients treated with SLED had a higher first postdialysis MAP than those treated with CVVH, which led to lower mortality. Further multicenter randomized clinical trials of larger sample size are needed to compare the effects of SLED and CVVH on the outcomes of postsurgical acute dialysis patients.

It has been known that the P1 and Lewis antigens on red blood cells (RBCs) affect the risk of Escherichia coli–related urinary tract infection. In the present study, we investigated the associations between those antigens and peritoneal dialysis (PD)–related peritonitis and E. coli peritonitis. We recruited 155 patients (66 men, 89 women) who were under PD treatment in July 2005, checked the P1 and Lewis antigen status of their RBCs, reviewed their medical charts, and recorded the dates and the causative pathogens of peritonitis episodes. The relationships between peritonitis and the antigens were analyzed. The mean age of these PD patients was 52.5 ± 14.9 years, and the mean PD duration was 39.8 ± 38.2 months. A total of 66 peritonitis episodes occurred (over 93.4 patient– months) in 41 patients, with 8 patients having more than 1 episode. In particular, E. coli peritonitis accounted for 16 of the 66 peritonitis episodes. We fitted two multiple Cox proportional hazards models (with the robust variance method) for predicting the hazard rates of peritonitis-free and E. coli peritonitis-free survival times to our right-censored data with recurrent events. We found that patients on PD treatment for less than 4 years with (A) lower serum albumin, (B) one or more previous peritonitis episodes, or (C) negative Lewis a and positive Lewis b antigens (secretor) would be at higher risk of peritonitis. And, conditioning on blood type, the PD patients with one or more previous peritonitis episodes and (A) positive P1 antigen, (B) negative Lewis a and positive Lewis b antigens (secretor), or (C) positive Lewis a and negative Lewis b antigens (non-secretor) would be at higher risk of E. coli peritonitis.

Background Particular attention should be paid to postoperative patients that suffer from severe acute kidney injury (AKI) requiring renal replacement therapy (RRT). Methods This multicenter prospective observational study included 342 patients with postoperative AKI requiring RRT from January 2002 to December 2006. Results There were 137 (40%) survivors at 90 days after the commencement of RRT. Independent predictors of 90-day mortality were older age, presence of sepsis, status post–cardiopulmonary resuscitation, necessity of continuous renal replacement therapy (CRRT), requirement of total parenteral nutrition, lower body mass index, higher Sequential Organ Failure Assessment score, and higher serum lactate level at the commencement of RRT. Further analysis among the survivors showed that lower serum creatinine at intensive care unit admission, lower Simplified Acute Physiology Score II and inotropic equivalent score at the commencement of RRT, and using CRRT were independent predictors for subsequent renal recovery. Conclusions The development of AKI requiring RRT in postoperative critical patients represents a substantial risk for mortality and morbidity.

Purpose The consumption of Chinese herbal products (CHPs) is increasing exponentially. However, the scientific evidence is lacking and there is an urgent requirement for detailed pharmacoepidemiological information on CHP usage. This study was to investigate CHP prescription patterns in Taiwan. Methods We carried out a cross-sectional analysis on a cohort of 200 000 patients based on 2004 data from the National Health Insurance (NHI) reimbursement database. Data mining techniques were applied to explore CHP co-prescription patterns. Results A total of 46 938 patients had been prescribed CHPs on at least one occasion in 2004. Patients using CHPs were generally female and middle-aged, made more outpatient visits, had fewer hospitalizations and consumed more medical resources than non-users of CHPs. A total of 1 073 030 CHPs were contained within 220 123 prescriptions, for which acute nasopharyngitis was the most common indication. Yan hu suo and Jia Wei Xiao Yao San were the most frequently prescribed single herb (SH) and herbal formula (HF), respectively. The results of the data mining showed that the best predictions were provided by co-prescriptions of ‘Mo yao and Ru xiang’, ‘Ye jiao teng and Suan Zao Ren Tan’ and ‘Dang Gui Nian Tong Tang and Shu Jing Huo Xue Tang’ in the groups of SH–SH, SH–HF and HF–HF, respectively. Conclusions This study provides national-level CHP prescription profiles and utilization rates, and documents, for the first time, HF–HF prescription combinations in Chinese medicine (CM) practices in Taiwan. We conclude that more studies are needed to validate the safety and effectiveness of CHP prescriptions. Copyright © 2008 John Wiley & Sons, Ltd.

Objective: This study examined the association between hospital mortality and five illness—severity scoring systems evaluated at different time points in the intensive care unit (ICU) as well as clinical variables as predictors in critically ill patients supported by extracorporeal membrane oxygenation (ECMO) and acute dialysis. Methods: This multicenter prospective observational study included 104 patients who received ECMO support and acute dialysis from January 2002 to December 2006. Patients’ demographic, clinical and laboratory variables were analyzed as predictors of survival. The SAPS2, APACHE II, SOFA, MODS, and SAPS 3 scores upon ICU admission and at acute dialysis commencement were evaluated to predict the patient’s hospital mortality. Results: Hospital mortality for the study group was 76% (79/104). Among the five scoringsystems,onlySAPS3score showeda significantdifference betweensurvivors andnon-survivorseitheruponICUadmission(p = 0.038)or at dialysis commencement (p = 0.001). SAPS 3 score at dialysis commencement showed the best discrimination ability by using the area under the receiver operating characteristic curve (SOFA, 0.55; SAPS 2, 0.56; MODS, 0.58; APACHE II, 0.59; and SAPS 3, 0.73). Multiple logistic regression analysis indicated that SAPS 3 score at dialysis commencement (OR: 1.070, 95% CI: 1.016—1.216) and IABP usage before ECMO (OR: 4.181, 95% CI: 1.448—12.075) were two independent risk factors for hospital mortality. Conclusions: Among five common ICU scoring systems evaluated at different time points, SAPS 3 at dialysis commencement is the best risk adjustment systems to predict hospital mortality in critically ill patients supported by ECMO and acute dialysis. Furthermore, the SAPS 3 score at dialysis commencement and IABP usage before ECMO are two major independent predictors for hospital mortality in patients supported by ECMO and acute dialysis. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background/Aims Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and novel therapies are urgently needed. Recently, aberrant expression of Aurora kinases has been reported in various human cancers including HCC. We sought to investigate the potential of a potent and selective Aurora kinase inhibitor, VE-465, for targeted therapy of HCC. Methods Cytotoxicity effects of VE-465 were tested in Huh-7 and HepG2 cell lines. Inhibition of Aurora kinase activity was demonstrated by Western blotting and immunofluorescence staining. Mitotic perturbation was visualized by confocal microscopy. Cell cycle profiles and apoptosis were assessed by flow cytometry. In vivo efficacy was determined in nude mice with human HCC xenografts. Results We demonstrated that VE-465 induced proliferation blockade, histone H3 (Ser10) dephosphorylation, mitotic disturbance, endoreduplication, and apoptosis in Huh-7 and HepG2 cells. We also found that VE-465 suppressed Aurora kinase activity, prevented tumor growth, and induced apoptosis in a Huh-7 xenograft model. Conclusions These findings show that VE-465 has potent anticancer effects in human HCC. Inhibitors of Aurora kinases may deserve further exploration as molecular targeted agents against HCC.

A predictive model for hospital mortality in postoperative acute renal failure (ARF) patients requiring renal replacement therapy (RRT) may aid clinicians' therapeutic decision-making and research design.A prospective observational study of 398 postoperative ARF patients requiring RRT was conducted in four hospitals. The derivation cohort consisted of 334 patients recruited between January 2002 and December 2005. The validation cohort consisted of 64 patients recruited between January 2006 and December 2006.The hospital mortality rates for the derivation and validation cohorts were 65.6 and 62.5%, respectively. A modified Sequential Organ Failure Assessment (SOFA) score was constructed at the commencement of RRT by a formula of serum lactate level (mM) + 2 x (generic SOFA score) + 3 x (age per decade) + 8 (if mechanical circulatory support required) + 10 (if total parenteral nutrition required) + 11 (if status postcardiopulmonary resuscitation) + 13 (if positive sepsis sign). The area under the receiver operating characteristic curve of the model for the derivation and validation cohorts was 0.804 and 0.839, respectively.This validated score at dialysis commencement might assist clinicians in estimating hospital mortality, planning future clinical trials, and providing quantitative guidance for decision making in postoperative ARF patients requiring RRT.

Background: Malnutrition-inflammation score (MIS) is a comprehensive and quantitative system to assess malnutrition-inflammation complex syndrome, and a strong correlation between MIS and morbidity/mortality in maintenance hemodialysis (MHD) patients had been demonstrated. However, there is no cut-off value of MIS to categorize patients into high risk or low risk patients. Methods: A total of 257 chronic stable and ambulatory adult MHD patients from Far Eastern Memorial Hospital were enrolled for the study. The MIS of each patient was recorded at the initiation of study and the study population was followed up as a 12-month prospective cohort to evaluate mortality as the primary outcome. Results: Twelve patients died in the 12-month observational period. Both multiple logistic regression analyses and Cox proportional hazards model denoted MIS, alkaline phosphatase, transferrin saturation, ferritin, and total iron binding capacity as significant predictors of 1-year mortality. The conditional effect plot of MIS on 1-year mortality revealed that when fixing the alkaline phosphatase, transferrin saturation, ferritin, and total iron binding capacity at a mean value, the probability of death for an MHD patient whose MIS was 3, 4, and 5 is 10, 40, and 80%, respectively. Conclusions: Our study shows that MHD patients with MIS score of more than 4–5 had a significant risk of 1-year mortality. Additional risk factors associated with short-term mortality besides malnutrition-inflammation complex syndrome were anemia and renal osteodystrophy. This study proves that MIS is a useful tool to risk-stratify Asian MHD patients and to identify those at risk of short-term death. Nutritional interventions that can improve the MIS may also improve survival, but this hypothesis needs to be verified in interventional studies.

We assessed the impact of lymphovascular invasion on the prognosis of patients treated for clinically localized (pT1-3N0M0) upper tract urothelial carcinoma.From January 1998 to December 2004, 106 patients treated surgically for clinically localized upper tract urothelial carcinoma (pT1-3cN0M0) were recruited for analysis retrospectively. We assessed the impact of multiple prognostic factors including age, sex, smoking, tumor multiplicity, pathological stage, grading, squamous differentiation, subsequent bladder tumor recurrence, tumor site and lymphovascular invasion on the recurrence-free survival rate. We clarified the role of lymphovascular invasion in predicting cancer specific survival in these patients.Mean patient age was 67.2 +/- 11.1 years and median followup was 47.5 months (range 40 to 115). Lymphovascular invasion was present in 32 of 106 (30.2%) patients. The 5-year recurrence-free survival rate in patients with and without lymphovascular invasion was 65.3% and 91.9%, respectively (p0.001). On multivariate analysis lymphovascular invasion status, pT3 and ureteral involvement were significant predictors of patient recurrence-free survival. The positivity of lymphovascular invasion was also significantly associated with the risk of higher stage disease (OR 7.49).Patients with lymphovascular invasion had a higher risk of greater pathological stage disease. Lymphovascular invasion and high stage disease with ureteral involvement led to a greater risk of disease recurrence and, in turn, recurrence caused a higher mortality rate. This finding could help identify patients at greater risk for disease recurrence who would benefit from close followup and early adjuvant therapy.

Purpose: KIAA0101 is a proliferating cell nuclear antigen–associated factor and involved in cell proliferation. This study is to elucidate its role in the progression, early tumor recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). Experimental Design: KIAA0101 mRNA was measured by reverse transcription-PCR in 216 resected, unifocal, primary HCCs and its protein in 164 cases by immunohistochemistry. Results: KIAA0101 mRNA was overexpressed in 131 (61%) HCCs, and protein was detected in 105 (64%). KIAA0101 mRNA overexpression correlated with higher tumor grade (P = 0.0001), higher tumor stage with vascular invasion and various extents of intrahepatic spread (P = 1 × 10−8), ETR (P = 1.8 × 10−6), and lower 5-year survival (P = 0.0026). Multivariate analysis confirmed that KIAA0101 overexpression was an independent risk factor associated with high-grade tumor (P = 0.0001), high-stage tumor (P < 0.0001), and ETR (P = 0.0052) and thus contributed to poor prognosis. KIAA0101 protein–positive tumor cells accumulated at the borders of tumor macrotrabeculae and were more abundant in tumor thrombi than in the main tumors. Hence, KIAA0101 may contribute to growth advantage and resistance to hypoxic insult. In this series, p53 mutation was detected in 93 of 184 (51%) HCCs. In both p53-mutated and non–p53-mutated HCCs, KIAA0101 overexpression correlated with higher vascular invasion (stages IIIA to IV; all Ps < 0.0001) and, accordingly, led to lower 5-year survival rates (P = 0.011 and 0.029, respectively). Conclusion: KIAA0101 correlates with enhanced metastatic potential and is a significant prognostic factor of HCC.

CD24, a mucin like cell surface adhesion molecule and a ligand for P-selectin, has been reported as a prognostic factor in a variety of human cancers. However, the role of CD24 in gastric adenocarcinoma remains largely unknown.The expression pattern of CD24 in 103 gastric adenocarcinomas (31 diffuse type, 60 intestinal type, and 12 mixed type) was analyzed by immunohistochemistry.Cytoplasmic CD24 expression occurred in 50% of the gastric adenocarcinoma patients and was associated with high-stage tumor (Stage III-IV, P = .023), serosal invasion (SI, P = .010), lymphovascular invasion (LVI, P = .039), and lower 10-year survival (P = .0238). The CD24 staining pattern was different in intestinal and diffuse-type gastric adenocarcinomas. However, the tumor thrombi in lymphovascular spaces exhibited strong cytoplasmic CD24 expression in both types. Further analysis showed that cytoplasmic CD24 expression was, in fact, correlated with high-stage tumor, SI, LVI, and lower 10-year survival significantly (P = .020, P = .007, P = .018, P = .0285, respectively) in diffuse-type gastric adenocarcinoma. Moreover, multivariate analysis showed that cytoplasmic CD24 expression was an independent risk factor of SI and LVI respectively (P = .0083 and P = .0019), and thus it contributed to high-stage tumor and poor patient survival in diffuse- or mixed-type gastric adenocarcinoma.Cytoplasmic expression of CD24 was associated with invasiveness and poorer prognosis and can serve as a novel target for prognostic prediction and adjuvant treatment of patients with diffuse-type gastric adenocarcinoma after tumor resection.

Background Infantile hepatitis B after neonatal immunoprophylaxis is a rare yet distinct disease. This study aimed to analyze the long-term outcomes and risk factors in immunized infants with hepatitis B. Methods The clinical parameters and outcomes of 41 infants born after universal immunization, and admitted for HBV-positive hepatitis were studied. All patients were followed for at least 6 months (median = 4.4 years, range 0.6–18.1 years). Patient survival, changes of HBsAg and HBeAg status, and complications were analyzed. Results Among the 41 cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20 with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses revealed younger age of onset (age

Limited data on the outcomes of adults with active sepsis undergoing extracorporeal membrane oxygenation (ECMO) exist.We analyzed our prospective database for adults undergoing their first ECMO from 2001 to 2009. Patients with preexisting sepsis had newly emerging or uncontrolled infections precipitating refractory respiratory and/or circulatory failure within 7 days preceding ECMO. Propensity score matching was performed to equalize potential prognostic factors between patients with and patients without sepsis.Of the 514 adults receiving their first ECMO, 108 with preexisting sepsis were matched with 108 without sepsis by propensity score. Overall survival to discharge did not differ between those with (28.7%) and those without sepsis (37.0%; P = .192). When venovenous ECMO and venoarterial ECMO were considered separately, survival tended to be worse for septic patients on venoarterial ECMO (24.4%) compared with nonseptic adults on venoarterial ECMO (34.9%; P = .147). After adjustments for age, stroke, acute myocarditis, inter-extracorporeal cardiopulmonary resuscitation, and post-ECMO renal and neurologic deficits by multivariate analysis, the increased risk of mortality persisted for septic adults receiving venoarterial ECMO (hazard ratio, 2.54; 95% confidence intervals, 1.75-3.70; P.01). Patients on venovenous ECMO had similar outcomes regardless of preexisting sepsis.Preexisting sepsis is not a contraindication for ECMO. However, venoarterial ECMO should be used with caution, given active sepsis.

Background There is no literature for stratification of permanent implantable venous ports (Port-A) related bloodstream infection (BSI) in solid cancer patients. We conduct this study to characterize the risk factors of BSI associated with the use of Port-A (PABSI) in solid cancer patients. Methods The study is done in a teaching hospital in Taiwan. Solid cancer patients who were implanted with a Port-A for systemic anti-cancer therapies were prospectively followed for the occurrence of PABSI, defined as BSI without other identifiable infection foci. Patients with PABSI during the follow-up period constitute the case cohort (N = 58) and 174 patients were randomly selected from those without BSI as the control cohort. PABSI risk score was developed by Cox proportional hazards model. Results 416 patients were registered (Table 1). Eighty-eight PABSI episodes occurred in 58 patients, with an incidence of 1.05 per 1000 catheter-days. All but one patient had stage 4 cancer. Independent predictors of PABSI occurrence included neutropenia (HR = 3.86, 95% CI = 1.75-8.50), total parental nutrition (TPN) (HR = 3.51, 95% CI = 1.86-6.63), chronic steroid use (HR = 7.01, 95% CI = 2.78-17.65), invasive procedure (HR = 3.00, 95% CI = 1.29-6.98), postoperative antibiotics (HR = 2.61, 95% CI = 1.43-4.75), and preoperative antibiotics (HR = 0.38, 95% CI = 0.17-0.83). A PABSI risk score, with a cut-off value of 0 (sensitivity 88.5%, specificity 64.3%), was defined for stage 4 cancer patients as follows: neutropenia, +1.350; TPN, +1.256; chronic steroid use, +1.947; preoperative antibiotics, –0.970; postoperative antibiotics, +0.959; and invasive procedure, +1.098. The median PABSI-free survival was 4.47 months for patients with score β0 but not reached for patients with score < 0 (p < 0.0001). Conclusions The PABSI risk score can help define high-risk groups in solid cancer patients and may help design future preventive strategies. Presence of any risk factor would render patients as high risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2656. doi:1538-7445.AM2012-2656

Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission.We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5-10 years old.A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P.0001 and.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%).Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.

Background Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival. Methods We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates. Results We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival. Conclusions Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients.

Purpose To evaluate the refractive status and optical components in school age children born prematurely and to examine the risk factors associated with refractive errors. Methods The participants were a cohort of children aged 7 to 9 years with gestational age less than 35 weeks or birth weight less than 1500 g. The participants' neonatal histories were reviewed; their refractive status and optical components were measured. The study results were compared with the results of age-matched children from a national survey. Results Of the 108 children studied, 48 (44%) had retinopathy of prematurity (ROP); 29 (27%) had ROP ≥ stage 3. Compared with the control subjects, the study cases showed higher prevalence of myopia (48% vs. 29%), hyperopia (23% vs. 15%), and astigmatism (73% vs. 41%). Common ocular features included shallow anterior chamber depth (ACD), thick lenses, and steep corneal curvature. The hyperopic cases had the shortest axial length (AL), whereas the myopia cases had significantly shallower ACD and greater LT. Those with a history of ROP had more prominent changes in the anterior segment. Generalized estimating equations showed that refractive errors could be predicted by a combination of optical components. Conclusions In children born prematurely, the development of myopia is mainly influenced by anterior segment components, whereas hyperopia is mainly attributable to short AL. Astigmatism is primarily cornea-related. A combination of various optical components results in complicated refractive outcomes. The presence of ROP may be associated with significantly shorter ACD, thicker lens, and higher myopia and astigmatism. (ClinicalTrials.gov number, NCT01045616.).

Background To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC). Methods The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines. Results Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis. Conclusion Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.

Background: We previously demonstrated that Aurora B overexpression correlated well with higher histology grade and more advanced stage of hepatocellular carcinoma (HCC). In this study, we sought to analyze the association between Aurora B overexpression and vascular invasion/metastasis of HCC, as well as the potential of AZD1152, a novel and selective Aurora B kinase inhibitor in preventing vascular invasion and metastasis of HCC. Method: Aurora B mRNA levels were measured in HCC and paired non-tumorous liver tissues by reverse transcription-PCR. One hundred and sixty surgically resected, primary unifocal HCCs were selected for this study. Vascular invasion was determined by pathologic examination. All 160 patients had been followed for more than 5 years or until death. Forty-nine patients developed extrahepatic tumor metastasis. Multivariate analysis was conducted to determine the significance of Aurora B overexpression on vascular invasion and metastasis of HCC. The effects of AZD1152 on tumor invasiveness were tested in Huh-7 and HA-27T HCC cell lines by migration and invasion assays. Results: Overexpression of Aurora B was found in 98 of the 160 (61%) primary HCC. Univariate analysis showed that vascular invasion and metastasis were both associated with younger age (≤ 55 years, P = 0.027 and P = 0.003, respectively), high α-fetoprotein levels (> 200 ng/mL, P < 0.001 and P = 0.008), large tumor size (> 5 cm, P < 0.001 and P < 0.001), higher tumor grade (grade III-IV, P < 0.001 and P = 0.025), as well as Aurora B overexpression (P < 0.001 and P < 0.001). Multivariate analysis confirmed that Aurora B overexpression was an independent risk factor associated with vascular invasion (odds ratio, 2.659; P = 0.0183) and metastasis (odds ratio, 4.195; P = 0.0027). AZD1152, 5-125 nM, induced dose-dependent inhibition on migration and invasion in Huh-7 and HA-27T cells. Conclusions: Overexpression of Aurora B correlates well with vascular invasion and metastasis of HCC. Inhibition of Aurora B kinase by small molecular inhibitors may suppress invasion and metastasis of HCC. Grant support: Grant NSC96-2628-B-002-054-MY3 from the National Science Council (Taiwan), Grant DOH97-TD-B-111-001 from the Department of Health (Taiwan), and Grant NSC98-3112-B-075A-001 from the National Science Council (Taiwan). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3290.

Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome. Methods A multicenter prospective observational study based on the NSARF (National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 ± 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006. Results The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality. Conclusions The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification.