Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

Relationship between HbA1c and Continuous Glucose Monitoring in Chinese Population: A Multicenter Study

Objective

Since there is a paucity of reference data in the literature to indicate the relationship between HbA1c, and 24 h mean blood glucose (MBG) from continuous glucose monitoring (CGM) in Chinese populations, we described the above relationship in adult Chinese subjects with different glucose tolerance status.

Methods

Seven-hundred-and-forty-two individuals without history of diabetes were included to the study at 11 hospitals in urban areas across China from 2007–2009 and data of 673 subjects were included into the final analysis. Oral glucose tolerance test (OGTT) classified the participants as nondiabetic subjects, including those with normal glucose regulation (NGR; n = 121) and impaired glucose regulation (IGR; n = 209), or newly diagnosed type 2 diabetes (n = 343). All participants completed testing for HbA1c levels and wore a CGM system for three consecutive days. The 24 h MBG levels were calculated. Spearman correlations and linear regression analyses were applied to quantify the relationship between glucose markers.

Results

The levels of HbA1c and 24 h MBG significantly increased with presence of glucose intolerance (NGR<IGR<type 2 diabetes; both, P<0.001). Analysis of the total population indicated that HbA1c was strongly correlated with 24 h MBG (r = 0.735). The correlation was also found to be significant for the subgroup of participants with newly diagnosed type 2 diabetes (r = 0.694, P<0.001). Linear regression analysis of the total study population yielded the following equation: 24 h MBG _mmol/L = 1.198×HbA1c–0.582 (24 h MBG _mg/dL = 21.564×HbA1c–10.476) (R² = 0.670, P<0.001). The model fit was not improved by application of exponential or quadratic modeling. When HbA1c was 6.5%, the calculated 24 h MBG was 7.2 (6.4–8.1) mmol/L (130 (115–146) mg/dL); and when HbA1c was 7.0%, the 24 h MBG was 7.8 (6.9–8.7) mmol/L (140 (124–157) mg/dL).

Conclusions

Our study provided the reference data of the relationship between HbA1c and CGM in Chinese subjects.     

Role of Toll-Like Receptor 4 in Colorectal Carcinogenesis: A Meta-Analysis

Objective

This meta-analysis was performed to evaluate the role of toll-like receptor 4 (TLR-4) in colorectal carcinogenesis.

Methods

The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through November 1st, 2013 without language restrictions. Odds ratios (ORs) or standardized mean differences (SMD) with their 95% confidence intervals (CI) were calculated.

Results

Fourteen case-control studies met the inclusion criteria for this meta-analysis. A total of 1,209 colorectal cancer (CRC) cases and 1,218 healthy controls were involved in this meta-analysis. Two common polymorphisms (299 A>G and 399 C>T) in the TLR-4 gene, TLR-4 mRNA and protein expression were assessed. Our meta-analysis results revealed that the TLR-4 399 C>T polymorphism might increase the risk of CRC (allele model: OR = 1.77, 95%CI = 1.32∼2.36, P<0.001; dominant model: OR = 1.83, 95%CI = 1.32∼2.52, P<0.001; respectively). However, we found no correlation between the TLR-4 299 A>G polymorphism and CRC risk (all P>0.05). A subgroup analysis by ethnicity suggested that TLR-4 genetic polymorphisms were associated with an increased risk of CRC among Asians (allele model: OR = 1.50, 95%CI = 1.19∼1.88, P = 0.001; dominant model: OR = 1.49, 95%CI = 1.16∼1.92, P = 0.002; respectively), but not among Caucasians and Africans (all P>0.05). Furthermore, our results showed that TLR-4 mRNA and protein levels in CRC patients were higher than those in healthy controls (TLR-4 mRNA: SMD  = 2.51, 95%CI  = 0.98∼4.05, P = 0.001; TLR-4 protein: OR  = 4.75, 95%CI  = 1.16∼19.36, P = 0.030; respectively).

Conclusion

Our findings provide empirical evidence that TLR-4 may play an important role in colorectal carcinogenesis. Thus, TLR-4 is a promising potential biomarker for the early diagnosis of CRC.     

Observational Cohort Study of Ventricular Arrhythmia in Adults with Marfan Syndrome Caused by FBN1 Mutations

Background

Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.

Methods and Results

We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro–brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24–32 (P = .021). Kaplan–Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24–32 (P<.001).

Conclusions

Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24–32 may be risk factors of VTE.     

The Pretreatment Albumin to Globulin Ratio Has Predictive Value for Long-Term Mortality in Nasopharyngeal Carcinoma

Background

Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC.

Methods

This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR.

Results

Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P  = 0.029) and DMFS (P  = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P  = 0.033), high neutrophil count (P  = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001).

Conclusion

The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.     

Poor Prognosis of Phosphatase of Regenerating Liver 3 Expression in Gastric Cancer: A Meta-Analysis

Background

Overexpression of phosphatase of regenerating liver 3 (PRL-3) has been implicated in gastric cancer (GC) metastasis. Epidemiological studies have evaluated the relationship between PRL-3 expression and prognosis in GC. However, results still remains controversial. In this study, a meta-analysis was performed to evaluate the association of PRL-3 expression with overall survival (OS) and clinicopathological characteristics.

Methods

Literature databases were searched to identify eligible studies dated until April 2013. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the association.

Results

A total of 1380 GC patients from six studies were included in the meta-analysis. Overall, the combined HR estimate for OS in a random-effect model was 1.89 (95% CI = 1.38–2.60; P<0.001). Results showed that PRL-3 overexpression was significantly associated with OS, indicating that it may be a biomarker for poor prognosis of GC. Both subgroup and sensitivity analyses further identified the prognostic role of PRL-3 expression in GC patients. Moreover, PRL-3 overexpression was significantly associated with tumor stage (OR = 2.25; 95% CI = 1.63–3.12; P<0.001), depth of invasion (OR = 2.03; 95% CI = 1.38–2.98; P<0.001), vascular invasion (OR = 2.52; 95% CI = 1.79–3.56; P<0.001), lymphatic invasion (OR = 3.74; 95% CI = 2.49–5.63; P<0.001), and lymph node metastasis (OR = 4.56; 95% CI = 2.37–8.76; P<0.001). However, when age, sex, tumor size, and tumor differentiation were considered, no obvious association was observed.

Conclusions

This meta-analysis reveals significant association of PRL-3 overexpression with OS and some clinicopathological features in GC. PRL-3 may be a predicative factor of poor prognosis and aggressive tumor behavior in GC patients.     

Prevalence and Associations of Incomplete Posterior Vitreous Detachment in Adult Chinese: The Beijing Eye Study

Purpose

To determine prevalence and associations of incomplete posterior vitreous detachment (PVD).

Methods

The population-based cross-sectional Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT). Incomplete PVD was differentiated into type 1 (shallow PVD with circular perifoveal vitreous attachment), type 2 (PVD reaching fovea but not foveola), type 3 (shallow PVD with pinpoint vitreous attachment at the foveola), and type 4 (PVD completely detached from the macula, attached to the optic disc).

Results

An incomplete PVD was detected in 3948 eyes (prevalence: 60.5±0.6%; 95% Confidence Interval (CI): 59.3%,61.7%) of 2198 subjects (67.1±0.8%;95%CI: 65.6%,68.7%). Type 1 PVD was seen in 3090 (78.3%) eyes, type 2 PVD in 504 (12.8%) eyes, type 3 PVD in 70 (1.8%) eyes, and type 4 PVD in 284 (7.2%) eyes. Prevalence of incomplete PVD was associated with younger age (P<0.001;OR:0.91), male gender (P<0.001;OR:0.64), rural region of habitation (P<0.001;OR:0.49), larger corneal diameter (P = 0.04;OR:0.91), better best corrected visual acuity (P = 0.02;OR:0.41), and hyperopic refractive error (P<0.001;OR:1.15). The type of incomplete PVD was associated with higher age (P<0.001), urban region of habitation (P<0.001), myopic refractive error (P = 0.001), thinner cornea (P = 0.005), and better best corrected visual acuity (P = 0.056).

Conclusions

In adult Chinese in Greater Beijing, prevalence of an incomplete PVD (detected in 67.1% subjects) was associated with younger age, male gender, rural region of habitation, larger corneal diameter, better best corrected visual acuity and hyperopic refractive error.     

Plasma MicroRNAs as Potential Noninvasive Biomarkers for In-Stent Restenosis

Objective

To investigate whether microRNAs (miRs) can serve as novel biomarkers for in-stent restenosis (ISR).

Methods

This retrospective, observational single-centre study was conducted at the cardiovascular department of a tertiary hospital centre in the north of China. Follow-up coronary angiography at 6 to 12 months was performed in 181 consecutive patients implanted with drug-eluting stents. Fifty-two healthy volunteers served as the control group. The plasma miRs levels were analyzed by quantitative real-time PCR. Receiver-operating characteristic curve (ROC) analysis was performed to investigate the characters of these miRs as potential biomarkers of ISR.

Results

MiR-21 levels in ISR patients were significantly higher than those in non-ISR patients and healthy controls (P<0.05), while miR-100 (P<0.05), miR-143 (P<0.001) and miR-145 (P<0.0001) levels were significantly decreased in ISR patients. Further analysis showed that miR-21 levels were remarkably increased (P = 0.045), while miR-100 (P = 0.041), miR-143 (P = 0.029) and miR-145 (P<0.01) levels were dramatically decreased in patients with diffuse ISR compared to those with focal ISR. ROC analysis demonstrated that the area under curve of miR-145, miR-143, miR-100 and miR-21 were 0.880 (95% confidence interval; CI = 0.791–0.987, P<0.001), 0.818 (95% confidence interval; CI = 0.755–0.963, P<0.001), 0.608 (95% confidence interval; CI = 0.372–0.757, P<0.05) and 0.568 (95% confidence interval; CI = 0.372–0.757, P<0.05), with specificity of 83.1%, 80.1%, 68.9% and 68.6%, and sensitivity of 88.7%, 82.1%, 60.2% and 50.1%, respectively.

Conclusions

Circulating miR-143 and miR-145 levels are associated with the occurrence of ISR and can serve as novel noninvasive biomarkers for ISR.     

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

Purpose

To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.

Methods

A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated.

Results

The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464–3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717–53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; P<0.001) and 9.419 (95% CI: 2.613–33.953; P = 0.001), respectively).

Conclusion

The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.     

Diabetic Retinopathy and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011

Purpose

The cerebrospinal fluid pressure (CSFP) is a major determinant of central retinal vein pressure and thus of retinal capillary pressure. We tested the hypothesis whether prevalence and severity of diabetic retinopathy are associated with CSFP.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. A detailed ophthalmic examination was performed including fundus photography for the assessment of diabetic retinopathy according. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44xBody Mass Index[kg/m²]+0.16 Diastolic Blood Pressure[mmHg]–0.18xAge[Years]−1.91.

Results

In binary regression analysis, presence of diabetic retinopathy was significantly associated with higher levels of HbA1c (P<0.001; regression coefficient B:0.25; odds ratio (OR):1.28; 95% confidence interval (CI):1.15,1.43), higher blood concentration of glucose (P<0.001; B:0.40;OR:1.49;95%CI:1.36,1.63), longer known duration of diabetes mellitus (P<0.001; B:0.14;OR:1.15; 95%CI:1.11,1.19), higher systolic blood pressure (P<0.001; B:0.03;OR:1.03;95%CI:1.02,1.04), lower diastolic blood pressure (P<0.001; B:−0.06;OR:0.94;95%CI:0.91,0.97), and higher CSFP (P = 0.002; B:0.13;OR:1.14;95%CI:1.05,1.24). Severity of diabetic retinopathy was significantly associated with higher HbA1c value (P<0.001; standardized coefficient beta: 0.19; correlation coefficient B: 0.07;95%CI:0.05,0.08), higher blood concentration of glucose (P<0.001; beta:0.18;B:0.04;95%CI:0.04,0.05), longer known duration of diabetes mellitus (P<0.001; beta:0.20;B:0.03;95%CI:0.02,0.03), lower level of education (P = 0.001; beta:−0.05;B:−0.02;95%CI:−0.03,−0.01), lower diastolic blood pressure (P = 0.002; beta:−0.08;B:−0.001;95%CI:−0.004,−0.001), higher systolic blood pressure (P = 0.006; beta:0.06;B:0.001;95%CI:0.000,0.001), and higher CSFP (P = 0.006; beta:0.06;B:0.006;95%CI:0.002,0.010).

Conclusions

Higher prevalence and severity of diabetic retinopathy were associated with higher estimated CSFP after adjusting for systemic parameters. Higher CSFP through a higher retinal vein pressure may lead to more marked retinal venous congestion and vascular leakage in diabetic retinae.     

Efficacy and Tolerability of Telaprevir for Chronic Hepatitis Virus C Genotype 1 Infection: A Meta-Analysis

Background

Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatic cirrhosis and hepatocellular carcinoma, and HCV genotype 1 is the most prevalent genotype and is resistant to current standard therapy. We performed this meta-analysis to evaluate the efficacy and safety of telaprevir-based therapy for chronic HCV genotype 1 infection.

Methods

We included randomized controlled trials with no year or language restriction. All data were analyzed using a random-effects model by Review Manager v5.0. The primary outcome was the proportion of patients achieving sustained virologic response (SVR), and the secondary outcomes were HCV relapse rate, incidence of severe adverse events (SAEs), and discontinuation due to adverse events.

Results

The proportion of achieving SVR was significantly higher in the telaprevir group (odds ratio [OR] = 3.40 [1.92, 6.00], P<0.0001; I² = 87%) regardless of a patients’ previous treatment status. It was also significantly higher in the 24-week and 48-week treatment groups (OR = 4.52 [2.08, 9.81], P<0.001; I² = 85%, and OR = 4.05 [1.56, 10.56], P = 0.004; I² = 92%, respectively), while it was comparable in the 12-week treatment group (OR = 1.32 [0.63, 2.75], P = 0.46; I² = 35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR = 0.28 [0.16, 0.49], P<0.001; I² = 76%). However, the incidence of SAE (OR = 1.56 [1.15, 2.10], P = 0.004; I² = 0%) and study discontinuation due to adverse events (OR = 2.24 [1.43, 3.50], P<0.001; I² = 37%) were significantly higher in the telaprevir group.

Conclusion

Despite its higher incidence of SAEs and discontinuation due to adverse events, telaprevir-based therapy can increase the proportion of achieving SVR in both previously treated and untreated chronic HCV-1 infected patients.     

Comparison of remission criteria in a tumour necrosis factor inhibitor treated rheumatoid arthritis longitudinal cohort: patient global health is a confounder

Introduction

Our objectives were to assess the frequency and sustainability of American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) and Disease Activity Score (DAS)28(4v)–C-reactive protein (CRP) remission 12 months after the initiation of tumour necrosis factor inhibitor (TNFi) therapy in a rheumatoid arthritis (RA) cohort.

Methods

Data were collected of 273 biologic naive RA patients at baseline, then 3, 6 and 12 months post-TNFi therapy. Remission status was calculated using DAS28(4v)-CRP <2.6 and ACR/EULAR Boolean criteria. Response was scored using EULAR criteria.

Results

Mean (range) patient age was 59.9 (7.2-85.4) years with disease duration of 13.4 (1.0-52.0) years. Responder status maintained from 3–12 months (86%, 82.4%), laboratory/clinical parameters (erythrocyte sedimentation rate (ESR), CRP, patient global health (PGH), DAS28(4v)-CRP) also showed sustained improvement (P < 0.05). DAS28 remission was reached by 102 subjects at 1 year, 27 patients were in Boolean remission, but 75 missed it from the DAS28 remission group. Patients in remission were younger (P = 0.041) with lower baseline tender joint count (TJC)28 and PGH than those not in remission (P = 0.001, P = 0.047). DAS28 remission patients were older (P = 0.026) with higher 12 months PGH and subsequently higher DAS28 than Boolean remission patients (P < 0.0001). Patients not achieving Boolean remission due to missing one subcriteria most frequently missed PGH ≤1 criteria (79.8%).

Conclusions

Only 10% of this TNFi treated cohort achieved remission according to the new ACR/EULAR criteria, which requires lower disease activity. More stringent criteria may ensure further resolution of disease activity and better longterm radiographic outcome, which supports earlier intervention with biologic therapy in RA.     

Associations between the Duration of Dialysis,Endotoxemia, Monocyte Chemoattractant Protein-1, and the Effects of a Short-Dwell Exchange in Patients Requiring Continuous Ambulatory Peritoneal Dialysis

Background

Endotoxemia is exaggerated and contributes to systemic inflammation and atherosclerosis in patients requiring continuous ambulatory peritoneal dialysis (CAPD). The risk of mortality is substantially increased in patients requiring CAPD for >2 years. However, little is known about the effects of long-term CAPD on circulating endotoxin and cytokine levels. Therefore, the present study evaluated the associations between plasma endotoxin levels, cytokine levels, and clinical parameters with the effects of a short-dwell exchange on endotoxemia and cytokine levels in patients on long-term CAPD.

Methods

A total of 26 patients were enrolled and divided into two groups (short-term or long-term CAPD) according to the 2-year duration of CAPD. Plasma endotoxin and cytokine levels were measured before and after a short-dwell exchange (4-h dwell) during a peritoneal equilibration test (a standardized method to evaluate the solute transport function of peritoneal membrane). These data were analyzed to determine the relationship of circulating endotoxemia, cytokines and clinical characteristics between the two groups.

Results

Plasma endotoxin and monocyte chemotactic protein-1 (MCP-1) levels were significantly elevated in the long-term group. PD duration was significantly correlated with plasma endotoxin (r = 0.479, P = 0.016) and MCP-1 (r = 0.486, P = 0.012). PD duration was also independently associated with plasma MCP-1 levels in multivariate regression. Plasma MCP-1 levels tended to decrease (13.3% reduction, P = 0.077) though endotoxin levels did not decrease in the long-term PD group after the 4-h short-dwell exchange.

Conclusion

Long-term PD may result in exaggerated endotoxemia and elevated plasma MCP-1 levels. The duration of PD was significantly correlated with circulating endotoxin and MCP-1 levels, and was an independent predictor of plasma MCP-1 levels. Short-dwell exchange seemed to have favorable effects on circulating MCP-1 levels in patients on long-term PD.     

Increased Risk of Developing Digestive Tract Cancer in Subjects Carrying the PLCE1 rs2274223 A>G Polymorphism: Evidence from a Meta-Analysis

Background

To date, the association between phospholipase C epsilon 1 (PLCE1) rs2274223 A>G and risk of digestive tract cancer (DTC) remains inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis on all eligible case–control studies involving 8281 cases and 10,532 controls.

Methods

A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and digestive tract cancer risk. The pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed or random effect model. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results

Overall, the PLCE1 rs2274223 A>G polymorphism was associated with risk of DTC in all genetic models (GA vs. AA: OR = 1.21, 95% CI = 1.14–1.29, P<0.001; GG vs. AA: OR = 1.30, 95% CI = 1.06–1.60, P = 0.012; GG/GA vs. AA: OR = 1.20, 95% CI = 1.10–1.32, P<0.001; GG vs. GA/AA: OR = 1.21, 95% CI = 1.01–1.46, P = 0.040). The recessive model did not reach statistically significance when the P values were Bonferroni corrected to 0.0125. In the stratified analysis by cancer type, ethnicity, and source of controls, significantly increased risk was observed for esophagus cancer, Asians in three genetic models (heterozygote comparison, homozygote comparison and dominant model), population-based studies in all genetic models, and for gastric cancer in the heterozygote comparison and dominant model after Bonferroni correction. However, in the subsite of gastric cancer, no significant association was found either in cardia or non-cardia gastric cancer.

Conclusion

Our study indicated that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of DTC, especially among Asian populations. Due to some minor limitations, our findings should be confirmed in further studies.     

A Pattern of Early Radiation-Induced Inflammatory Cytokine Expression Is Associated with Lung Toxicity in Patients with Non-Small Cell Lung Cancer

Purpose

Lung inflammation leading to pulmonary toxicity after radiotherapy (RT) can occur in patients with non-small cell lung cancer (NSCLC). We investigated the kinetics of RT induced plasma inflammatory cytokines in these patients in order to identify clinical predictors of toxicity.

Experimental Design

In 12 NSCLC patients, RT to 60 Gy (30 fractions over 6 weeks) was delivered; 6 received concurrent chemoradiation (chemoRT) and 6 received RT alone. Blood samples were taken before therapy, at 1 and 24 hours after delivery of the 1^st fraction, 4 weeks into RT, and 12 weeks after completion of treatment, for analysis of a panel of 22 plasma cytokines. The severity of respiratory toxicities were recorded using common terminology criteria for adverse events (CTCAE) v4.0.

Results

Twelve cytokines were detected in response to RT, of which ten demonstrated significant temporal changes in plasma concentration. For Eotaxin, IL-33, IL-6, MDC, MIP-1α and VEGF, plasma concentrations were dependent upon treatment group (chemoRT vs RT alone, all p-values <0.05), whilst concentrations of MCP-1, IP-10, MCP-3, MIP-1β, TIMP-1 and TNF-α were not. Mean lung radiation dose correlated with a reduction at 1 hour in plasma levels of IP-10 (r² = 0.858, p<0.01), MCP-1 (r² = 0.653, p<0.01), MCP-3 (r² = 0.721, p<0.01), and IL-6 (r² = 0.531, p = 0.02). Patients who sustained pulmonary toxicity demonstrated significantly different levels of IP-10 and MCP-1 at 1 hour, and Eotaxin, IL-6 and TIMP-1 concentration at 24 hours (all p-values <0.05) when compared to patients without respiratory toxicity.

Conclusions

Inflammatory cytokines were induced in NSCLC patients during and after RT. Early changes in levels of IP-10, MCP-1, Eotaxin, IL-6 and TIMP-1 were associated with higher grade toxicity. Measurement of cytokine concentrations during RT could help predict lung toxicity and lead to new therapeutic strategies.     

Peripapillary Arterial Circle of Zinn-Haller: Location and Spatial Relationships with Myopia

Purpose

To measure histomorphometrically the location of the peripapillary arterial circle of Zinn-Haller (ZHAC) and assess its associations with axial length.

Methods

Using a light microscope, we measured the distance from the ZHAC to the peripapillary ring (optic disc border), the merging point of the dura mater with the posterior sclera (“dura-sclera point”), and the inner scleral surface. In the parapapillary region, we differentiated between beta zone (presence of Bruch''s membrane, absence of retinal pigment epithelium) and gamma zone (absence of Bruch''s membrane). The peripapillary scleral flange as roof of the orbital cerebrospinal fluid space was the connection between the end of the lamina cribrosa and the posterior full-thickness sclera starting at the dura-sclera point.

Results

The study included 101 human globes (101 patients) with a mean axial length of 26.7±3.7 mm (range: 20.0–39.0 mm). The distance between the ZHAC and the peripapillary ring increased significantly with longer axial length (P<0.001; correlation coefficient r = 0.49), longer parapapillary gamma zone (P<0.001;r = 0.85), longer (P<0.001;r = 0.73) and thinner (P<0.001;r = −0.45) peripapillary scleral flange, and thinner sclera posterior to the equator (P<0.001). ZHAC distance to the peripapillary ring was not significantly associated with length of parapapillary beta zone (P = 0.33). Including only non-highly myopic eyes (axial length <26.5 mm), the ZHAC distance to the disc border was not related with axial length (P = 0.84). In non-highly myopic eyes, the ZHAC was located close to the dura-sclera point. With increasing axial length and decreasing thickness of the peripapillary scleral flange, the ZHAC was located closer to the inner scleral surface.

Conclusions

The distance between the ZHAC and the optic disc border is markedly enlarged in highly myopic eyes. Since the ZHAC is the main arterial source for the lamina cribrosa blood supply, the finding may be of interest for the pathogenesis of the increased glaucoma susceptibility in highly myopic eyes.     

Dickkopf-1 as a Novel Predictor Is Associated with Risk Stratification by GRACE Risk Scores for Predictive Value in Patients with Acute Coronary Syndrome: A Retrospective Research

Objective

Dickkopf-1 (DKK-1), a major regulator of the Wnt pathway, plays an important role in cardiovascular disease. However, no study has evaluated the association of DKK-1 and acute coronary syndrome (ACS). We investigated this association and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score predicting major adverse cardiac events (MACE) can be improved by adding the DKK-1 value.

Methods

We enrolled 291 patients (46 with ST-segment elevation myocardial infarction [STEMI] and 245 with non-ST elevated ACS [NSTE-ACS]) who were divided into groups by tertiles of baseline plasma DKK-1 level measured by ELISA. The GRACE risk score was calculated and predictive value alone and together with DKK-1 and/or high-sensitivity C-reactive protein (hs-CRP) level were assessed, respectively.

Results

Compared with patients with NSTE-ACS, those with STEMI had higher plasma DKK-1 level at baseline (P = 0.006). Plasma DKK-1 level was correlated with hs-CRP level (r = 0.295, P<0.001) and was greater with high than intermediate or low GRACE scores (P = 0.002 and P<0.001, respectively). We found 44 (15.1%) MACEs during a median 2-year follow-up. DKK-1 levels were higher for patients with than without events (P<0.001). The rate of MACE increased with increasing DKK-1 level (P<0.001). The area under the receiver operating characteristic curve for GRACE score with MACE was 0.524 and improved to 0.791 with the addition of hs-CRP level, 0.775 with the addition of DKK-1 level and 0.847 with both values added.

Conclusions

DKK-1 is an independent predictor of long-term MACE of patients with ACS. The long-term predictive ability of post-discharge GRACE score may be enhanced by adding DKK-1 level.     

Prevalence and Risk Factors of Fluid Overload in Southern Chinese Continuous Ambulatory Peritoneal Dialysis Patients

Background

Fluid overload is frequently present in CAPD patients and one of important predictors of mortality. The aim of this study is to investigate the prevalence and associated risk factors in a cohort study of Southern Chinese CAPD patients.

Methods

The patients (receiving CAPD 3 months and more) in our center were investigated from January 1, 2008 to December 31, 2009. Multi-frequency bioelectrical impedance analysis was used to assess the patient’s body composition and fluid status.

Results

A total of 307 CAPD patients (43% male, mean age 47.8±15.3 years) were enrolled, with a median duration of PD 14.6 (5.9–30.9) months. Fluid overload (defined by Extracellular water/Total body water (ECW/TBW)≥0.40) was present in 205 (66.8%) patients. Univariate analysis indicated that ECW/TBW were inversely associated with body mass index (r = −0.11, P = 0.047), subjective global assessment score (r = −0.11, P = 0.004), body fat mass (r = −0.15, P = 0.05), serum albumin (r = −0.32, P<0.001), creatinine (r = −0.14, P = 0.02), potassium (r = −0.15, P = 0.02), and residual urine output (r = −0.14, P = 0.01), positively associated with age (r = 0.27, P<0.001), Chalrlson Comorbidity Index score (r = 0.29, P<0.001), and systolic blood pressure (r = 0.22, P<0.001). Multivariate linear regression showed that lower serum albumin (β = −0.223, P<0.001), lower body fat mass (β = −0.166, P = 0.033), old age (β = 0.268, P<0.001), higher systolic blood pressure (β = 0.16, P = 0.006), less residual urine output (β = −0.116, P = 0.042), and lower serum potassium (β = −0.126, P = 0.03) were independently associated with higher ECW/TBW. After 1 year of follow-up, the cardiac event rate was significantly higher in the patients with fluid overload (17.1% vs 6.9%, P = 0.023) than that of the normal hydrated patients.

Conclusions

The prevalence of fluid overload was high in CAPD patients. Fluid overload in CAPD patients were independently associated with protein-energy wasting, old age, and decreased residual urine output. Furthermore, CAPD patients with fluid overload had higher cardiac event rate than that of normal hydrated patents.     

Study of 320-Slice Dynamic Volume CT Perfusion in Different Pathologic Types of Kidney Tumor: Preliminary Results

Objective

To investigate microcirculatory differences between pathologic types of kidney tumor using 320-slice dynamic volume CT perfusion.

Methods

Perfusion imaging with 320-slice dynamic volume CT was prospectively performed in 85 patients with pathologically proven clear cell renal cell carcinoma (RCC) (n = 66), papillary RCC (n = 7), chromophobe RCC (n = 5), angiomyolipoma (AML) with minimal fat (n = 7), or RCC (n = 78). Equivalent blood volume (Equiv BV), permeability surface-area product (PS; clearance/unit volume = permeability), and blood flow (BF) of tumor and normal renal cortex were measured and analyzed. Effective radiation dose was calculated.

Results

There was a significant difference in all three parameters between tumor and normal renal cortex (P<0.001). Equiv BV was significantly different between RCC and AML with minimal fat (P = 0.038) and between clear cell RCC and AML with minimal fat (P<0.001). Mean Equiv BV and BF were significantly higher in clear cell RCC than in papillary RCC (P<0.001 for both) and mean Equiv BV was higher in clear cell RCC than in chromophobe RCC (P<0.001). The effective radiation dose of the CT perfusion protocol was 18.5 mSv.

Conclusion

Perfusion imaging using 320-slice dynamic volume CT can be used to evaluate hemodynamic features of the whole kidney and kidney tumors, which may be useful in the differential diagnosis of these four pathologic types of kidney tumor.     

Serum CXCL9 Levels Are Associated with Tumor Progression and Treatment Outcome in Patients with Nasopharyngeal Carcinoma

Objectives

The aim of this cohort study was to examine the role of the chemokine (C-X-C motif) ligand 9 (CXCL9) on nasopharyngeal carcinoma (NPC).

Materials & Methods

Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay.

Results

CXCL9 expression was significantly higher in tumors than in normal epithelium. CXCL9 serum concentrations were also significantly higher in NPC patients compared to those in healthy individuals (516.8±617.6 vs. 170.7±375.0 pg/mL, P<0.0001). Serum CXCL9 levels were significantly higher in NPC patients with higher tumor stages, nodal stages, and overall stages (P<0.001, P = 0.001, and P<0.001, respectively). We found a statistically significant correlation between the concentrations of CXCL9 and EBV DNA load in the NPC patients (Spearman’s correlation analysis; r = 0.473, P<0.001; 95% confidence interval, 0.346–0.582). Moreover, NPC patients with higher CXCL9 levels (>290 pg/mL, median) before treatment had worse prognoses for overall survival and disease-free survival (P = 0.045 and P = 0.008, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for disease-free survival (P = 0.015).

Conclusion

Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of NPC tumors and the serum level of this ligand may be useful as a prognostic indicator.