Evaluation of Uric Acid as a Prognostic Blood-Based Marker in a Large Cohort of Pancreatic Cancer Patients

Background

Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC.

Patients and Methods

Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated.

Results

None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077–1.751; p = 0.011).

Conclusion

In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.     

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

Background

Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery.

Methods

Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models.

Results

Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001).

Conclusion

The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality.     

Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease

Background

Periodontitis and Alzheimer disease (AD) are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD.

Methods

Using a case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up), matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a cohort of longitudinally followed northern Manhattan residents aged >65 years. Mean follow-up was five years (SD 2.6). In baseline sera, serum IgG levels were determined for bacteria known to be positively or negatively associated with periodontitis (Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans Y4, Treponema denticola, Campylobacter rectus, Eubacterium nodatum, and Actinomyces naeslundii genospecies-2). In all analyses, we used antibody threshold levels shown to correlate with presence of moderate-severe periodontitis.

Results

Mean age was 72 years (SD 6.9) for controls, and 79 years (SD 4.6) for cases (p<0.001). Non-Hispanic Whites comprised 26%, non-Hispanic Blacks 27%, and Hispanics 48% of the sample. In a model adjusting for baseline age, sex, education, diabetes mellitus, hypertension, smoking, prior history of stroke, and apolipoprotein E genotype, high anti-A. naeslundii titer (>640 ng/ml, present in 10% of subjects) was associated with increased risk of AD (HR = 2.0, 95%CI: 1.1–3.8). This association was stronger after adjusting for other significant titers (HR = 3.1, 95%CI: 1.5–6.4). In this model, high anti-E. nodatum IgG (>1755 ng/ml; 19% of subjects) was associated with lower risk of AD (HR = 0.5, 95%CI: 0.2–0.9).

Conclusions

Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD.     

The Association of Uremic Toxins and Inflammation in Hemodialysis Patients

Background

Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear.

Methods

We conducted a cross-sectional study to evaluate the association of the serum uremic toxins and inflammatory markers in hemodialysis patients.

Results

The uremic toxins were not associated with inflammatory markers- including high sensitivity C-reactive protein, IL(Interleukin) -1β, IL-6, tumor necrosis factor-α. In multiple linear regression, serum levels of total p-cresol sulfate (PCS) were independently significantly associated with serum total indoxyl sulfate (IS) (standardized coefficient: 0.274, p<0.001), and co-morbidity of diabetes mellitus (DM) (standardized coefficient: 0.342, p<0.001) and coronary artery disease (CAD) (standardized coefficient: 0.128, p = 0.043). The serum total PCS levels in hemodialysis with co-morbidity of DM and CAD were significantly higher than those without co-morbidity of DM and CAD (34.10±23.44 vs. 16.36±13.06 mg/L, p<0.001). Serum levels of total IS was independently significantly associated with serum creatinine (standardized coefficient: 0.285, p<0.001), total PCS (standardized coefficient: 0.239, p = 0.001), and synthetic membrane dialysis (standardized coefficient: 0.139, p = 0.046).

Conclusion

The study showed that serum levels of total PCS and IS were not associated with pro-inflammatory markers in hemodialysis patients. Besides, serum levels of total PCS were independently positively significantly associated with co-morbidity of CAD and DM.     

Dental Prophylaxis Decreases the Risk of Esophageal Cancer in Males; A Nationwide Population-Based Study in Taiwan

Background

Periodontal disease (PD) is one of the most common chronic inflammatory diseases. Esophageal cancer (EC) is also a common cause of death due to cancer among males. Systemic inflammatory processes have been shown to increase the risk of cancer. We conducted a retrospective cohort study to investigate the association between PD and EC.

Methods

A total of 718,409 subjects were recruited from the Taiwan National Health Insurance Research Database (NHIRD) and followed from January 1, 2000 to December 31, 2010. Of these, 519,831 subjects were diagnosed with PD and were grouped according to the most advanced treatment they received: dental prophylaxis, intensive treatment, or no treatment. The IRs of EC were compared among groups.

Results

A total of 682 patients developed EC, resulting in an overall IR of 0.11 case-number per 1000 person-years (‰/y). The dental prophylaxis group had a significantly lower IR of EC (0.06‰/y) than other groups (p<0.001). Multivariable Cox regression analysis further revealed that male subjects [hazard ratio (HR) = 10.04, 95% confidence interval (CI)  = 7.58–13.30], as well as a history of esophageal ulcers (HR = 7.10, 95% CI = 5.03–10.01), alcohol abuse (HR = 5.46, 95% CI = 2.26–13.18), or esophageal reflux (HR = 1.86, 95% CI = 1.02–3.52), were factors associated with a higher risk of EC. And the dental prophylaxis group showed a significantly lower risk for EC (HR = 0.53, 95% CI = 0.44–0.65). Further subgroup analysis showed that the dental prophylaxis group among males had a significant lower risk (HR = 0.54, 95% CI = 0.44–0.66) for EC, while that of the females did not has statistically significant difference.

Conclusion

For this cohort, subjects received dental prophylaxis reduced the risk of EC compared to all PD and no PD groups among males.     

Serum Uric Acid Is Associated with Left Ventricular Hypertrophy Independent of Serum Parathyroid Hormone in Male Cardiac Patients

Background

Several studies have shown that serum uric acid (UA) is associated with left ventricular (LV) hypertrophy. Serum levels of parathyroid hormone (PTH), which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown.

Purpose

We investigated whether the relationship between serum uric acid (UA) and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients.

Methods and Results

In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65±12 years) who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001) but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48–5.28, P = 0.002 per one standard deviation increase).

Conclusions

Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.     

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.     

Prognostic Role of MicroRNA-221 in Various Human Malignant Neoplasms: A Meta-Analysis of 20 Related Studies

Background

MicroRNA-221 (miR-221) has been shown to play an important role in cancer prognosis. In order to evaluate the predictive value of miR-221, we compiled the evidence from 20 eligible studies to perform a meta-analysis.

Design

All of relevant studies were identified by searching PubMed, Embase, and Web of Science, and were assessed by further quality evaluation. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of total and stratified analyses, for overall survival (OS) and recurrence-free survival (RFS), were calculated to investigate the association between high miR-221 expression and cancer prognosis.

Results

We found that high miR-221 expression can predict a poor OS in malignant tumors (pooled HR = 1.55, P = 0.017) but has no significant association with RFS (pooled HR = 1.02, P = 0.942). Further in stratified analyses, high miR-221 expression was significantly associated with a poor OS in Asians (pooled HR = 2.04, P = 0.010) or serum/ plasma subgroup (pooled HR = 2.28, P<0.001), and even showed significantly poor OS (pooled HR = 1.80, P<0.001) and RFS (pooled HR = 2.43, P = 0.010) in hepatocellular carcinoma (HCC) subgroup, but was correlated to a favorable RFS in prostate cancer subgroup (pooled HR = 0.51, P = 0.004).

Conclusions

Our findings demonstrate that miR-221 is more suitable to predict cancer prognosis in Asians, and it is a promising prognostic biomarker for HCC. The detection of miR-221 in serum or plasma samples may make it become an effective method for monitoring patients'' prognosis and assessing therapeutic efficacy in the future.     

Plasma Uric Acid Levels Correlate with Inflammation and Disease Severity in Malian Children with Plasmodium falciparum Malaria

Background

Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA) precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs) and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of ‘parasite-derived’ UA stimulate immune cells to produce inflammatory cytokines in vitro.

Methods and Findings

We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β) in 470 Malian children presenting with uncomplicated malaria (UM), non-cerebral severe malaria (NCSM) or cerebral malaria (CM). UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09–1.35, n = 23, p = 0.0007) and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97–1.41, n = 9, p = 0.0890) compared to those with UM (median 4.60 mg/dl, n = 438). In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001), IL-10 (r = 0.242, p<0.00001), sTNFRII (r = 0.221, p<0.00001), MCP-1 (r = 0.220, p<0.00001), IL-8 (r = 0.147, p = 0.002), TNFα (r = 0.132, p = 0.006) and IP-10 (r = 0.120, p = 0.012)]. In 39 children, UA levels were 1.49-fold (95% CI 1.34–1.65; p<0.0001) higher during their malaria episode [geometric mean titer (GMT) 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl).

Conclusions

Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA and renal function may be involved. Defining pathogenic roles for parasite-derived UA precipitates, which we have not directly studied here, requires further investigation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00669084","term_id":"NCT00669084"}}NCT00669084     

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

Purpose

We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.

Patients and Methods

In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.

Results

Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).

Conclusions

Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.     

Elevated Serum Triglyceride and Retinol-Binding Protein 4 Levels Associated with Fructose-Sweetened Beverages in Adolescents

Background

The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production.

Objectives

This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents.

Methods

We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates.

Results

Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r = 0.253 to 0.404), but not among non-drinkers.

Conclusions

High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4.     

Meta-Analysis of Randomised Clinical Trials Comparing Idarubicin + Cytarabine with Daunorubicin + Cytarabine as the Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukaemia

Background

To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.

Methods

A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.

Results

Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07–1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45–0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81–0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80–1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.

Conclusion

Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.     

Inverse Association between Glycated Albumin and Insulin Secretory Function May Explain Higher Levels of Glycated Albumin in Subjects with Longer Duration of Diabetes

Background

Glycated albumin (GA) has been increasingly used as a reliable index for short-term glycemic monitoring, and is inversely associated with β-cell function. Because the pathophysiologic nature of type 2 diabetes (T2D) is characterized by progressive decline in insulin secretion, the aim was to determine whether GA levels were affected by diabetes duration in subjects with T2D.

Methods

To minimize the effect of glucose variability on GA, subjects with stably maintained HbA_1c levels of <0.5% fluctuation across 6 months of measurements were included. Patients with newly diagnosed T2D (n = 1059) and with duration>1 year (n = 781) were recruited and categorized as New-T2D and Old-T2D, respectively. Biochemical, glycemic, and C-peptide parameters were measured.

Results

GA levels were significantly elevated in HbA_1c-matched Old-T2D subjects compared to New-T2D subjects. Duration of diabetes was positively correlated with GA, whereas a negative relationship was found with C-peptide increment (ΔC-peptide). Among insulin secretory indices, dynamic parameters such as ΔC-peptide were inversely related to GA (r = −0.42, p<0.001). Multiple linear regression analyses showed that duration of diabetes was associated with GA (standardized β coefficient [STDβ] = 0.05, p<0.001), but not with HbA_1c (STDβ = 0.04, p<0.095). This association disappeared after additional adjustment with ΔC-peptide (STDβ = 0.02, p = 0.372), suggesting that β-cell function might be a linking factor of close relationship between duration of diabetes and GA values.

Conclusions

The present study showed that GA levels were significantly increased in subjects with longer duration T2D and with decreased insulin secretory function. Additional caution should be taken when interpreting GA values to assess glycemic control status in these individuals.     

Hyponatremia as a Predictor of Mortality in Peritoneal Dialysis Patients

Background and Aim

Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients.

Methods

This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients.

Results

Among the baseline parameters, serum sodium level was positively associated with serum albumin (β = 0.145; p = 0.003) and residual renal function (RRF) (β = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (β = −0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73–0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70–0.85; p<0.001) deaths.

Conclusions

This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately.     

Lymphotoxin Alpha (LTA) Polymorphism Is Associated with Prognosis of Non-Hodgkin’s Lymphoma in a Chinese Population

Background

Non-Hodgkin’s lymphoma (NHL) has been widely reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the survival and prognosis of NHL patients. To evaluate the role of such genetic variations in prognosis of NHL, we conducted this study in a Chinese population.

Methods

We used the TaqMan assay to genotype six single nucleotide polymorphisms (SNPs) (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T) for 215 NHL cases. Kaplan-Meier analysis was performed to compare progression free survival among two common genotypes. Cox proportional hazard models were used to identify independent risk factors.

Results

We observed that LTA rs1800683G>A was significantly associated with risk of progression or relapse in NHL patients (HR = 1.63, 95%CI = 1.06–2.51; P = 0.028), particularly in Diffuse large B cell lymphoma (DLBCL) cases (HR = 1.50, 95%CI = 1.10–2.04, P = 0.01). Both univariate and multivariate Cox regression analysis showed that in DLBCL patients, Ann Arbor stage III/IV, elevated LDH level before treatment and LTA rs1800683 AA genotype carrier were independent risk factors for progression or relapse. While in NK/T cell lymphoma, Ann Arbor stage III/IV and elevated β₂-MG level before treatment indicated poorer prognosis.

Conclusions

The polymorphism of LTA rs1800683G>A contributes to NHL prognosis in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.     

Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04–9.22) and the incidence density was 2.03 (95% CI = 1.75–2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10–2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39–18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18–3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30–2.77), and aspirin use (HR = 1.65; 95% CI = 1.22–2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75–1.82) and being female (HR = 1.12; 95% CI = 0.84–1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use.

Conclusions

After a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of cardiovascular events. However, further studies with patients at high cardiovascular and metabolic risk are needed to clarify this issue.     

Early Hemoperfusion May Improve Survival of Severely Paraquat-Poisoned Patients

Background

Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2−4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown.

Methods

We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed.

Results

The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16–0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39–0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05–0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24–0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables.

Conclusion

The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.     

Iron,Hepcidin and Inflammatory Status of Young Healthy Overweight and Obese Women in Australia

Background and Aims

Evidence suggests obesity-related inflammation alters iron metabolism potentially increasing the risk of iron deficiency. This cross-sectional study aimed to investigate iron, hepcidin and inflammatory status in young, healthy overweight and obese women.

Methods

114 young (18–25 years), healthy comorbidity-free women with a body mass index (BMI) ≥27.5 kg/m² were recruited. Biochemical data were analysed using mean ± standard deviation or median (interquartile range) and multivariate modelling. Biochemical markers were also stratified according to varying degrees of overweight and obesity.

Results

Anaemia (haemoglobin <120 g/l) and iron deficiency (serum ferritin <15.0 µg/l) were prevalent in 10% and 17% of participants respectively. Mean/median soluble transferrin receptor was 1.61±0.44 mg/l; hepcidin 6.40 (7.85) ng/ml and C-reactive protein (CRP) 3.58 (5.81) mg/l. Multivariate modelling showed that BMI was a significant predictor of serum iron (coefficient = -0.379; standard error = 0.139; p = 0.008), transferrin saturation (coefficient = -0.588; standard error = 0.222; p = 0.009) and CRP (coefficient = 0.127; standard error = 0.024; p<0.001). Stratification of participants according to BMI showed those with ≥35.0 kg/m² had significantly higher CRP (p<0.001) than those in lower BMI categories.

Conclusions

Increasing obesity was associated with minor disturbances in iron metabolism. However, overall outcomes indicated simple iron deficiency (hypoferritinaemia) was the primary iron-related abnormality with no apparent contribution of inflammation or hepcidin, even in those with BMI >35.0 kg/m². This indicates that obesity alone may not be sufficient to induce clinically significant disturbances to iron metabolism as previously described. This may be attributed to the lack of comorbidity in this cohort.     

The Prognostic Role of the Class III β-Tubulin in Non-Small Cell Lung Cancer (NSCLC) Patients Receiving the Taxane/Vinorebine-Based Chemotherapy: A Meta-Analysis

Background

A number of studies have examined the relationship between the expression of the class III β-tubulin (TUBB3) and the treatment responses to the taxane/vinorebine-based chemotherapy in patients with non-small cell lung cancer (NSCLC). However, the results of these studies were inconsistent and inconclusive. Therefore, we conducted an up-to-date meta-analysis to evaluate the prognostic role of TUBB3 in the taxane/vinorebine-based chemotherapy.

Methods

A literature search for relevant studies was conducted in PubMed, Embase, and CNKI. The inclusion criteria were the taxane/vinorebine-based chemotherapy in patients with NSCLC and the evaluation of the clinical outcomes in relation to the expression of TUBB3. The clinical outcomes analyzed in this study included the overall response rate (ORR), overall survival (OS), and event-free survival (EFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the risk associated with the TUBB3 expression in the taxane/vinorebine-based chemotherapy.

Results

A total of 28 studies with 2401 NSCLC patients were qualified for this meta-analysis. We found that the positive or high level of TUBB3 expression was associated with a poorer ORR (OR = 0.24, 95% CI = 0.16–0.36, p<0.001), an unfavorable OS (HR = 1.52, 95% CI = 1.27–1.82, p<0.001), and a worse EFS (HR = 1.47, 95% CI = 1.24–1.74, p<0.001) compared to the negative or low level of TUBB3 expression. The statistically significant associations between TUBB3 and chemotherapy responses were also observed in the stratified subgroup analysis, which included the analysis by ethnic subgroup (Asian and Caucasian), chemotherapy regimen (taxane-based and vinorebine-based), TUBB3 detection method (IHC and PCR), and treatment strategy (surgery plus adjuvant chemotherapy and palliative chemotherapy).

Conclusions

The expression level of TUBB3 may be a useful biomarker to predict the clinical outcomes of the taxane/vinorebine-based chemotherapy in patients with NSCLC.     

Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

Background

There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.

Methods

Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.

Results

Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV₁] <80% of predicted value). The mean FEV₁ decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV₁>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV₁ decline. Initial FEV₁>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).

Conclusions

NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.