Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

Background

Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC.

Methods

A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors.

Results

Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043).

Conclusions

Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC.     

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

Background

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.

Objective

To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.

Methods

Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.

Results

GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).

Conclusion

Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.     

Elevated High-Sensitivity C-Reactive Protein Levels Predict Decreased Survival for Nasopharyngeal Carcinoma Patients in the Intensity-Modulated Radiotherapy Era

Purpose

This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era.

Patients and Methods

In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS).

Results

Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238–2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273–2.064; p<0.001) and DMFS (HR:1.879; 95%CI:1.394–2.531; p<0.001). In subgroups such as advanced-stage group, low EBV DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased 4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs. 94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0% (p<0.001) for DMFS. A similar finding was observed for patients with cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs. 97.6% (p = 0.002) for DMFS.

Conclusion

Elevated serum hs-CRP levels were correlated with poor survival for NPC patients in the IMRT era, playing a complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level was still an effective indicator for patients with chronic HBV infection and cardiovascular disease.     

Healthcare Service Utilization for Practicing Physicians: A Population-Based Study

Background

Physicians are considered to be the most informed consumers in the use of medical services since they have more information about diseases or medical technology. However, although plenty of researchers have suggested that different medical seeking behavior exists among physicians, very few empirical studies have been conducted to investigate differences in medical utilization between physicians and the general population.

Objective

We explored differences in the utilization of healthcare services between physicians and the general population using a population-based dataset.

Design

A cross-sectional study.

Participants

Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 1426 physicians and 1426 sex- and age-matched comparison subjects.

Methods

We used Wilcoxon-Mann-Whitney tests to explore differences in variables of healthcare resource utilization between physicians and comparison subjects. We further used Kruskal-Wallis tests to examine differences in variables of healthcare resource utilization between physician practice location and comparison subjects.

Results

We found that physicians had significantly fewer outpatient visits (13.2 vs. 15.7, p<0.001) and significantly lower outpatient costs (US$477 vs. US$680, p<0.001) than comparison subjects. Furthermore, physicians had lower total health service costs than comparison subjects (US$643 vs. US$1066, p<0.001). This indicates that the mean total health service costs in the year 2010 was 1.66-fold greater for comparison subjects than for physicians. We also found that there were significant differences in the mean number of outpatient services (p<0.001), outpatient costs (p = 0.001), inpatients costs (p = 0.018), and total costs (p = 0.001) among office-based physicians, hospital-based physicians, and comparison subjects. Specifically, Scheffe contrast tests showed that office-based physicians had significantly more outpatient visits (19.3 vs.10.7, p<0.001) and significantly higher outpatient costs (US$656 vs. US$402, p<0.001) than hospital-based physicians.

Conclusions

Physicians had less healthcare utilization than comparison subjects. Furthermore, hospital-based physicians had higher inpatient costs and less outpatient services and costs than office-based physicians.     

Increased Risks of Mortality and Atherosclerotic Complications in Incident Hemodialysis Patients Subsequently with Bone Fractures: A Nationwide Case-Matched Cohort Study

Background

Hemodialysis (HD) patients with bone fractures have an increased risk for death. However, the risks for mortality and atherosclerotic complications in incident HD patients subsequently with bone fractures are unknown.

Methods

Data derived from the Taiwan National Health Institute Research Database between January 1997 and December 2008 was analyzed. The enrolled patients included 3,008 incident HD patients subsequently with a single long bone fracture (LB Fx) and 2,070 incident HD patients subsequently with a single non-long bone fracture (NLB Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of HD with incident HD patients who had no fractures and outcomes were measured over a 3-year follow-up.

Results

After demographic and co-morbidity adjustment, LB Fx increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR = 1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx.

Conclusions

The rates of mortality and stroke were significantly higher in incident HD patients subsequently with bone fractures than in matched patients without bone fractures. Incident HD patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx and without bone fractures. Thus, incident HD patients subsequently with bone fractures should be closely followed for a higher mortality and possible development of atherosclerotic complications.     

BRAFV600E Mutation Analysis in Patients with Metastatic Colorectal Cancer (mCRC) in Daily Clinical Practice: Correlations with Clinical Characteristics,and Its Impact on Patients’ Outcome

Background

To prospectively evaluate the usefulness of the BRAFV600E mutation detection in daily clinical practice in patients with metastatic Colorectal Cancer (mCRC).

Patients and Methods

504 mCRC patients treated with systemic chemotherapy ± biologics were analyzed.

Results

A statistically significant higher incidence of the BRAF mutation was observed in patients with ECOG-PS 2 (p=0.001), multiple metastatic sites (p=0.002),> 65 years old (p=0.004), primary tumors located in the colon (p<0.001), high-grade tumors (p=0.001) and in those with mucinous features (p=0.037). Patients with BRAFV600E mutated tumors had a statistically significantly reduced progression-free survival (PFS) compared to wild-type (wt) ones (4.1 and 11.6 months, respectively; p<0.001) and overall survival (OS) (14.0 vs. 34.6 months, respectively; p<0.001). In the multivariate analysis the BRAFV600E mutation emerged as an independent factor associated with reduced PFS (HR: 4.1, 95% CI 2.7–6.2; p<0.001) and OS (HR: 5.9, 95% CI 3.7–9.5; p<0.001). Among the 273 patients treated with salvage cetuximab or panitumumab, the BRAFV600E mutation was correlated with reduced PFS (2.2 vs. 6.0 months; p<0.0001) and OS (4.3 vs. 17.4 months; p<0.0001).

Conclusions

The presence of BRAFV600E-mutation in mCRC characterizes a subgroup of patients with distinct biologic, clinical and pathological features and is associated with very poor patients’ prognosis.     

Dysphagia in Acute Stroke: Incidence,Burden and Impact on Clinical Outcome

Background

Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke.

Methods

We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia.

Results

Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality.

Conclusion

Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.     

Do the Levels of Maternal Plasma Trace Elements Affect Fetal Nuchal Translucency Thickness?

Objective

Fetal nuchal translucency (NT) thickness is an important marker for prenatal screening; however, studies focusing on the correlation between maternal trace element levels and NT thickness are limited. The aim of this study was to evaluate maternal trace element levels during the first trimester and to investigate the association between maternal trace element levels and fetal NT thickness.

Methods

In total, 113 samples were obtained from singleton pregnant women. Maternal plasma samples were collected in the first trimester of gestation. Plasma trace element levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Nuchal translucency thickness was measured using ultrasonography at 10–14 weeks of gestation.

Results

We found that maternal plasma potassium (K) levels had a significant negative correlation with both NT (r = -0.230, p < 0.05) and NT Multiples of the Median (NT MoM) (r = -0.206, p < 0.05). After adjustment for potential confounders, log-transformed maternal plasma potassium levels in the first trimester were significantly associated with fetal NT (NT MoM: β = -0.68, p < 0.05; NT: β = -1.20, p < 0.01). Although not statistically significant, the As, Hg and Pb levels in maternal plasma were positively correlated with NT, and the Mg, Cu, Zn, Na and Ca levels were negatively correlated with NT.

Conclusion

Maternal plasma K levels during the first trimester appeared to be associated with NT thickness. The essential elements tended to decrease NT thickness, and non-essential elements tended to increase it.     

The Humanistic and Economic Burden of Restless Legs Syndrome

Objectives

To evaluate the humanistic and economic burden of a restless legs syndrome (RLS) diagnosis with regard to health-related quality of life, work productivity loss, healthcare resource use, and direct and indirect costs.

Study Design

Self-reported data came from the 2012 National Health and Wellness Survey (NHWS), a large, annual, nationally representative cross-sectional general health survey of US adults.

Methods

RLS patients (n = 2,392) were matched on demographic and health characteristics to Non-RLS respondents via propensity score matching differences between groups were tested with Bivariate and multivariable analyses.

Results

RLS patients had significantly lower health-related quality of life scores: Mental Component Summary (44.60 vs. 48.92, p<.001), Physical Component Summary (40.57 vs. 46.78, p<.001), Health Utilities (.63 vs. .71, p<.001) and higher levels of work productivity loss in the past seven days including absenteeism (8.1% vs. 9.3%, p<.001), presenteeism (26.5% vs. 15.8%, p<.001), and overall productivity loss (30.1% vs. 18.1%, p<.001) as well as general activity impairment (46.1% vs. 29.7%, p<.001). RLS patients had significantly higher healthcare resource use in the past 6 months than non-RLS patients: healthcare provider visits (7.46 vs. 4.42%, p<.001), ER visits (0.45 vs. 0.24, p<.001), and hospitalizations (0.24 vs. 0.15, p<.001). RLS patients also had higher estimated direct and indirect costs than non-RLS patients. Finally, it was found that across outcomes increasing severity is associated with increased economic and humanistic burden for RLS patients.

Conclusions

RLS patients suffer a greater humanistic and economic burden than those without RLS. Moreover as severity increases so does the burden of RLS.     

Association of Pretreatment Anemia with Pathological Response and Survival of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based Study

Background

Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT).

Methods

From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT.

Results

166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001).

Conclusions

Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup.     

Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV

Objective

To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).

Design

24-week randomized open-label prospective evaluation.

Method

Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls.

Results

At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log₁₀ HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log₁₀ HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group.

Conclusions

A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART.     

Female Gender and Differences in Outcome after Isolated Coronary Artery Bypass Graft Surgery: Does Age Play a Role?

Introduction

Female gender is a known risk factor for early and late mortality after coronary artery bypass graft surgery (CABG). Higher age of women at operation may influence outcome, since age per se is also an important risk factor. The purpose of our study was to analyze possible gender differences in outcome after isolated CABG in different age groups to delineate the impact of female gender and age.

Methods

All patients over 60 years of age undergoing isolated CABG at our department during 2001 and 2011 were included and categorized by age into sexagenarians (2266, 16.6% women), septuagenarians (2332, 25.4% women) and octogenarians (374, 32% women) and assessed by gender for 30-day and 180-day mortality.

Results

Thirty-day mortality was significantly higher in women only amongst septuagenarians (7.1 vs. 4.7%, p = 0.033). Same differences apply for 180-day mortality (12.3 vs. 8.2%, p = 0.033) and estimated one-year survival (81.6 ± 4.2 vs. 86.9 ± 2.2%, p = 0.001). Predictive factors for 30-day mortality of septuagenarian were logistic EuroSCORE (ES) (p = 0.003), perioperative myocardial infarction (MI) (p<0.001), pneumonia (p<0.001), abnormal LV-function (p<0.04) and use of LIMA graft (p<0.001), but not female gender. However, female gender was found to be an independent predictor for 180-day mortality (HR 1.632, p = 0.001) in addition to ES, use of LIMA graft, perioperative MI, pneumonia and abnormal LV function (HR 1.013, p = 0.004; HR 0.523, p<0.001; HR 2.710, p<0.001; HR 3.238, p<0.001; HR 2.013, p<0.001).

Conclusion

Women have a higher observed probability of early death after CABG in septuagenarians. However, female gender was not found to be an independent risk factor for 30-day, but for 180-day survival. Therefore, reduction of high impact risk factors such as perioperative MI and enhancement of LIMA use should be future goals. In view of our findings, decision for surgical revascularization should not be based on gender.     

The Predictive Value of Serum Squamous Cell Carcinoma Antigen in Patients with Cervical Cancer Who Receive Neoadjuvant Chemotherapy followed by Radical Surgery: A Single-Institute Study

Objective

Neoadjuvant chemotherapy (NACT) could affect the levels of squamous cell carcinoma antigen (SCC-Ag). This study evaluates the predictive value of pre- and posttreatment SCC-Ag levels in patients with cervical cancer who were treated with NACT followed by radical surgery.

Methods

A total of 286 patients with Stage IB1-IIIB squamous cell carcinoma of the uterine cervix who were treated with NACT followed by radical hysterectomy were analyzed retrospectively. The relationship between SCC-Ag levels, the clinicopathologic parameters, the response to NACT and the three-year survival rate was investigated.

Results

The levels of SCC-Ag were elevated (>3.5 ng/mL) in 43.8% of patients before NACT, and 13.0% of patients after NACT. Pre- and posttreatment levels of SCC-Ag correlated with the response to NACT (P = 0.010, and P<0.001), deep stromal infiltration (P = 0.041, and P = 0.006), and lymph node status (P<0.001, and P<0.001). In the multivariate analysis, the elevated pretreatment level of SCC-Ag was demonstrated to be an independent risk factor for Lymph node metastases (P<0.001). Patients with both pre- and posttreatment SCC-Ag levels ≤3.5 ng/mL showed the best 3-year disease-free survival (DFS) and 3-year overall survival (OS) compared with patients with either pre- or posttreatment levels >3.5 ng/mL (P<0.001, and P<0.001, respectively). A multivariate analysis showed that posttreatment SCC-Ag levels were a strong independent predictor of OS (P = 0.001) and DFS (P = 0.012).

Conclusion

Elevated pretreatment levels of SCC-Ag (>3.5 ng/mL) indicated a poor response to NACT and a higher risk of lymph node metastases. Elevated posttreatment levels of SCC-Ag were correlated with poor DFS and OS.     

Differential Expression of Lipid Metabolism-Related Proteins in Different Breast Cancer Subtypes

Purpose

This study aimed to determine the expression and clinical significance of proteins that are involved in lipid metabolism in human breast tumors.

Methods

Tumors from 476 breast cancer patients were used to construct tissue microarrays. Then, immunohistochemistry (IHC) for hormone-sensitive lipase (HSL), Perilipin 1 (PLIN1), fatty acid binding protein 4 (FABP4), carnitine palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX-1), and fatty acid synthase (FASN) was performed on these microarrays.

Results

Breast tumors were classified into 4 subtypes: luminal A (n = 242; 50.8%), luminal B (n = 134; 28.2%), human epidermal growth factor receptor 2 (HER2) (n = 50; 10.5%), and triple negative breast cancer (TNBC) (n = 50; 10.5%). The expression of PLIN1 (p < 0.001), FABP4 (p = 0.029), CPT-1A (p = 0.001), ACOX-1 (p < 0.001), and FASN (p < 0.001) differed significantly among these tumor subtypes. Notably, PLIN1, CPT-1A, and FASN expression was highest in HER2 tumors and lowest in TNBC tumors. Similarly, the expression of FABP4 and ACOX-1 was highest in HER2 tumors and lowest in luminal A tumors. In addition, ACOX-1 positivity was associated with significantly shorter overall survival (p = 0.018). When tumor subtype was considered, FABP4 positivity was associated with significantly shorter disease-free survival (p = 0.005) and overall survival (p = 0.041) in TNBC.

Conclusion

Lipid metabolism-related proteins are differentially expressed in different IHC subtypes of breast cancer and some are associated with decreased survival rates.     

The Practicability of a Novel Prognostic Index (PI) Model and Comparison with Nottingham Prognostic Index (NPI) in Stage I–III Breast Cancer Patients Undergoing Surgical Treatment

Background

Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors.

Methods

A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC).

Results

The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169–1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653–3.724, p< 0.001).

Conclusions

The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.     

Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients

Background

There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients.

Methods

We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles.

Results

The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377–3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147–4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178–3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167–6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005–2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171–2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761–3.250, P = 0.222; HR = 1.432, 95%CI: 0.108–19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211–2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547–3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921–4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685–5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620–3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625–3.568, P<0.001).

Conclusions

The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.     

Hypoglycemia and Medical Expenses in Patients with Type 2 Diabetes Mellitus: An Analysis Based on the Korea National Diabetes Program Cohort

Background and Aims

Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice.

Materials and Methods

We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea.

Results

During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001), had more hospital visits (121.94±126.88 days/PY, p < 0.001), had a longer hospital stays (16.13±29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001) than subjects without hypoglycemia.

Conclusion

Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system.     

Peripheral Blood Mononuclear Cells HIV DNA Levels Impact Intermittently on Neurocognition

Objectives

To determine the contribution of peripheral blood mononuclear cells’ (PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV-associated neurocognitive disorders (HAND) in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART).

Methods

Eighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points.

Results

At baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05). Log₁₀ HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 10⁶ PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04), and higher in those with no ART treatment during HIV infection 1st year (p = .03). Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor-coordination (p = .02-.12) to a lesser extent.

Conclusions

PBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression.     

Effects of Thiazolidinedione Therapy on Inflammatory Markers of Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Background

Inflammation is a common feature in patients with type 2 diabetes mellitus (T₂DM). This meta-analysis aimed to assess the influence of thiazolidinedione (TZD) therapy on the circulating levels of inflammatory markers in patients with T₂DM.

Methods and Results

We searched the databases Medline, Embase, ScienceDirect, Web of Science, SpringerLink, and the Cochrane Library for randomized controlled trials (RCTs) that examined the effects of thiazolidinedione vs. a placebo on patients with T₂DM. The main outcomes were absolute changes in levels of circulating inflammatory markers. Twenty-seven RCTs were included and data were analyzed using a fixed-effect model or a random-effect model based on heterogeneity. Pooled results indicated that circulating levels of high-sensitivity C reactive protein (hsCRP; SMD = –0.65, 95% CI = –0.98 to –0.32, p < 0.01), monocyte chemoattractant protein-1 (MCP-1; WMD = –54.19, 95% CI = –73.86 to –34.52, p < 0.01), von Willebrand factor% (vWF%; WMD = –8.18, 95% CI = –13.54 to –2.81, p 0.01), fibrinogen (SMD = –0.26, 95% CI = –0.41 to –0.11, p < 0.01) and E-selectin(WMD = –3.57, 95% CI = –5.59 to -1.54, p <0.01) were significantly decreased after TZD therapy. However, interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand, plasminogen activator inhibitor 1 (PAI-1) and intercellular adhesion molecule (ICAM-1) were not significantly affected. Subgroup analyses of PAI-1, vWF% and fibrinogen in terms of trial drugs showed significant reductions for rosiglitazone (all p valuses< 0.05), but not pioglitazone treatment. Conversely, the E-selectin (p < 0.01) lowering effect only existed in the pioglitazone group. Further, rosiglitazone and pioglitazone treatment reduced serum hsCRP and MCP-1 but had no marked effects on MMP-9, IL-6 and ICAM-1.

Conclusions

Limited evidence suggested that TZD therapy had anti-inflammatory property that might contribute to its beneficial effect on inflammatory state in patients with type 2 diabetes.