Influence of Preoperative Serum Aspartate Aminotransferase (AST) Level on the Prognosis of Patients with Non-Small Cell Lung Cancer

The purpose of this work is to analyze preoperative serum aspartate aminotransferase (AST) levels and their effect on the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical operation. These analyses were performed retrospectively in patients with NSCLC followed by surgery; participants were recruited between January 2004 and January 2008. All clinical information and laboratory results were collected from medical records. We explored the association between preoperative serum AST and recurrence-free survival (RFS), and the overall survival (OS) of NSCLC patients. Kaplan–Meier analysis and Cox multivariate analysis, stratified by the AST median value, were used to evaluate the prognostic effect. A chi-squared test was performed to compare clinical characteristics in different subgroups. A p-value of ≤0.05 was considered to be statistically significant. A total of 231 patients were enrolled. The median RFS and OS were 22 and 59 months, respectively. The AST levels were divided into two groups, using a cut-off value of 19 U/L: High AST (>19 U/L), n = 113 vs. low AST (≤19 U/L), n = 118. Multivariate analysis indicated that preoperative serum AST > 19 U/L (hazard ratio (HR) = 0.685, 95% confidence interval (CI): 0.493–0.994, p = 0.046 for RFS, HR = 0.646, 95% CI: 0.438–0.954, p = 0.028 for OS) was an independent prognostic factor for both RFS and OS. High preoperative serum AST levels may serve as a valuable marker to predict the prognosis of NSCLC after operation.     

Role of Serum Cholesterol and Statin Use in the Risk of Prostate Cancer Detection and Tumor Aggressiveness

The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p < 0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p < 0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p = 0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p = 0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p = 0.012). NSC men had a 53.8% rate of HGPCa, while the rate was only 27.6% in HSC men (p < 0.001). NSC men on statins had an HGPCa rate of 70.2%, while non-statin users had a rate of 41.2% (p < 0.001). The HGPCa rate for HSC men on statins was 18.8%, while the rate was 30.0% (p = 0.011) for non-users. Logistic regression analysis suggested that serum cholesterol levels could serve as an independent predictor of PCa risk, OR 1.87 (95% CI 1.56–2.24) and HGPCa risk, OR 0.31 (95% CI 0.23–0.44), while statin usage could not. Statin treatment may prevent PCa detection through serum cholesterol-mediated mechanisms. A disturbing increase in the HGPCa rate was observed in statin users who normalized their serum cholesterol.     

Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni- and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC.     

Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients

In this retrospective pilot study, the DNA-methylation status of genes that have been demonstrated to be involved in melanoma carcinogenesis was analyzed in order to identify novel biomarkers for the risk assessment of melanoma patients. We analyzed DNA extracted from punch-biopsies from 68 formalin-fixed paraffin-embedded (FFPE) melanoma specimens. Using MethyLight PCR, we examined 20 genes in specimens from a training set comprising 36 melanoma patients. Selected candidate genes were validated in a test set using FFPE tissue samples from 32 melanoma patients. First, we identified the TNFRSF10D DNA-methylation status (TNFRSF10D methylated vs. unmethylated) as a prognostic marker for overall (p = 0.001) and for relapse-free survival (p = 0.008) in the training set. This finding was confirmed in the independent test set (n = 32; overall survival p = 0.041; relapse-free survival p = 0.012). In a multivariate Cox-regression analysis including all patients, the TNFRSF10D DNA-methylation status remained as the most significant prognostic parameter for overall and relapse-free survival (relative-risk (RR) of death, 4.6 (95% CI: 2.0–11.0; p < 0.001), RR of relapse, 7.2 (95% CI: 2.8–18.3; p < 0.001)). In this study, we demonstrate that TNFRSF10D DNA-methylation analysis of a small tissue-punch from archival FFPE melanoma tissue is a promising approach to provide prognostic information in patients with melanoma.     

Association between Serum Soluble CD154 Levels and Mortality in Patients with Malignant Middle Cerebral Artery Infarction

Background: CD154 and its soluble counterpart (sCD154) are proteins of the tumor necrosis factor (TNF) family and exhibit proinflamatory and procoagulant properties. Higher circulating sCD154 levels have been found in ischemic stroke patients than in controls. However, the association between circulating sCD154 levels and mortality in ischemic stroke patients has not been reported, and was the focus of this study. Methods: This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We measured serum sCD154 from 50 patients with severe malignant middle cerebral artery infarction (MMCAI), defined as Glasgow Coma Scale (GCS) lower than 9, at the moment of the severe MMCAI diagnosis and from 50 healthy controls. The end-point of the study was 30-day mortality. Results: We found higher serum sCD154 levels in patients with severe MMCAI than in healthy controls (p < 0.001). We found higher serum sCD154 levels (p < 0.001) in non-surviving (n = 26) than in surviving MMCAI patients (n = 24). Multiple binomial logistic regression analysis showed that serum sCD154 levels >1.41 ng/mmL were associated with 30-day mortality (OR = 10.25; 95% CI = 2.34–44.95; p = 0.002). Conclusions: The new more important finding of our study was that serum sCD154 levels in MMCAI patients were associated with mortality.     

High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Lysosomal-associated membrane protein 3 (LAMP3), identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC) is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC). Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001). LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037). Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17–3.09, p = 0.010) and disease-free survival (HR = 1.80, 95% CI = 1.18–2.74, p = 0.006). In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.     

Impact of Serum Chemerin Levels on Liver Functional Reserves and Platelet Counts in Patients with Hepatocellular Carcinoma

Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma (HCC) patients and on the recurrence and prognosis of HCC. This study included 44 patients with any stage of HCC who underwent curative treatment at Gifu Municipal Hospital (Gifu, Japan) between 2006 and 2007. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Serum albumin levels (Pearson’s correlation coefficient; r = 0.3110, p = 0.0399), platelet counts (r = 0.4159, p = 0.0050), and prothrombin times (r = 0.3775, p = 0.0115) were significantly correlated with serum chemerin levels in patients with HCC, and they were inversely correlated with Child-Pugh scores (r = −0.3732, p = 0.0126), serum alanine aminotransferase levels (r = −0.3864, p = 0.0105), and total bilirubin levels (r = −0.4023, p = 0.0068). Among these variables, a multiple comparison test identified that platelet counts and total bilirubin levels were associated with serum chemerin levels (p < 0.0083). No significant correlation was found between serum chemerin levels and recurrence-free survival (p = 0.3691) or overall survival (p = 0.7916). In HCC patients, serum chemerin concentrations were correlated with liver functional reserves and platelet counts, but not with recurrence or prognosis.     

Adipsin Serum Concentrations and Adipose Tissue Expression in People with Obesity and Type 2 Diabetes

(1) Adipsin is an adipokine that may link increased fat mass and adipose tissue dysfunction to obesity-related cardiometabolic diseases. Here, we investigated whether adipsin serum concentrations and adipose tissue (AT) adipsin mRNA expression are related to parameters of AT function, obesity and type 2 diabetes (T2D). (2) Methods: A cohort of 637 individuals with a wide range of age and body weight (Age: 18–85 years; BMI: 19–70 kg/m²) with (n = 237) or without (n = 400) T2D was analyzed for serum adipsin concentrations by ELISA and visceral (VAT) and subcutaneous (SAT) adipsin mRNA expression by RT-PCR. (3) Results: Adipsin serum concentrations were significantly higher in patients with T2D compared to normoglycemic individuals. We found significant positive univariate relationships of adipsin serum concentrations with age (r = 0.282, p < 0.001), body weight (r = 0.264, p < 0.001), fasting plasma glucose (r = 0.136, p = 0.006) and leptin serum concentrations (r = 0.362, p < 0.001). Neither VAT nor SAT adipsin mRNA expression correlated with adipsin serum concentrations after adjusting for age, sex and BMI. Independent of T2D status, we found significantly higher adipsin expression in SAT compared to VAT (4) Conclusions: Our data suggest that adipsin serum concentrations are strongly related to obesity and age. However, neither circulating adipsin nor adipsin AT expression reflects parameters of impaired glucose or lipid metabolism in patients with obesity with or without T2D.     

The Role of Circulating MicroRNA-126 (miR-126): A Novel Biomarker for Screening Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus

Recent studies suggested an association of endothelial microRNA-126 (miR-126) with type 2 diabetes mellitus (T2DM). In the current study, we examined whether circulating miR-126 is associated with T2DM and pre-diabetic syndrome. The study included 82 subjects with impaired glucose tolerance (IGT), 75 subjects with impaired fasting glucose (IFG), 160 patients with newly diagnosed T2DM, and 138 healthy individuals. Quantitative polymerase chain reaction (qPCR) was used to examine serum miR-126. Serum miR-126 was significantly lower in IGT/IFG subjects and T2DM patients than in healthy controls (p < 0.05). After six months of treatment (diet control and exercise in IGT/IFG subjects, insulin plus diet control and exercise in T2DM patients), serum miR-126 increased significantly (p < 0.05). An analysis based on serum miR-126 in the sample revealed a significantly higher odds ratio (OR) for the subjects with the lowest 1/3 of serum miR-126 for T2DM (OR: 3.500, 95% confidence interval: 1.901–6.445, p < 0.05) than subjects within the highest 1/3 of serum miR-126. Such an association was still apparent after adjusting for other major risk factors. The area under the curve (AUC) for the receiver-operating characteristic (ROC) analysis was 0.792 (95% confidence interval: 0.707–0.877, p < 0.001). These results encourage the use of serum miR-126 as a biomarker for pre-diabetes and diabetes mellitus, as well as therapeutic response.     

Individual and Joint Impacts of Ethanol Use,BMI, Age and Gender on Serum Gamma-Glutamyltransferase Levels in Healthy Volunteers

Excessive ethanol consumption, obesity and increasing age may all lead to increased serum levels of gamma-glutamyltransferase (GGT) enzyme, which plays a key role in the metabolism of extracellular reduced glutathione. However, as yet, the interactions between the various modulators of GGT activities have remained poorly defined. We analyzed data from 15,617 apparently healthy individuals (7254 men and 8363 women, mean age 46 ± 13 years, range 25–74 years) who participated in a national cross-sectional health survey in Finland between 1997 and 2007. All subjects underwent detailed clinical examinations and interviews, including the amount of ethanol use and smoking habits. GGT levels were measured from all participants, and the individual and joint impacts of the different study variables on GGT levels were assessed. Significant individual effects were noted for ethanol use (p < 0.001), body mass index (BMI) (p < 0.001), age (p < 0.001) and smoking (p < 0.001). In men, significant two-factor interactions occurred between ethanol use and age (p < 0.020). Among those over 40 years of age, ethanol consumption was found to be a stronger determinant of increased GGT levels than in men below 40 years, whereas in the latter age group, BMI was found to predominate. In women, a significant two-factor interaction occurred between ethanol and BMI (p = 0.010), whereas it did not with ethanol use and age. The data underscores the role of ethanol consumption and age as major determinants of increased GGT levels in men, whereas in women, a relatively stronger impact was noted for ethanol intake and BMI. In light of the ability of GGT enzyme to modulate crucial redox-sensitive functions, the present findings also support the use of GGT as a biomarker of oxidative stress.     

Prognostic Value of Tumor Markers,NSE, CA125 and SCC,in Operable NSCLC Patients

The aim of this study was to investigate the prognostic value of tumor markers in operable non-small cell lung cancer (NSCLC) patients. A total of 481 NSCLC patients were enrolled in the present study. High levels of neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) were detected in 306 (63.6%), 89 (18.5%) and 125 (26.0%) patients, respectively. Seventy-eight of 481 patients died of disease progression, and the median disease-free survival (DFS) and overall survival (OS) were 16.0 and 21.0 months, respectively. The three-year DFS rate was 56.7%, and the OS rate was 75.3%. For serum NSE, the three-year cumulative DFS rate for the normal and elevated group was 67.7% and 51.8% (p = 0.007). The OS in patients with high and normal levels of NSE was 34.0 months and 48.0 months, respectively. The median DFS was 46.0 months versus 32.0 months (p = 0.001), and the OS was 48.0 months versus 44.0 months (p = 0.001) in patients with normal and high levels of CA125. For patients with squamous cell carcinoma, the overall survival was significantly shorter in patients with elevated levels of SCC (p = 0.041). In the multivariate analysis high levels of NSE, CA125 and clinical stage were significantly correlated with worse prognosis (p < 0.05). Patients with all three tumor markers elevated presented the worst prognosis (p < 0.05). In our analysis, high levels of preoperative serum NSE and CA125 are correlated with worse survival in operable NSCLC patients.     

5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature

Background: Glioblastoma multiforme (GBM) is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR) was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA) induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR) rate was 75.4% (95% CI: 67.4–83.5, p < 0.001). The mean time to tumor progression (TTP) was 8.1 months (95% CI: 4.7–12, p < 0.001). The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001). The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001) and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001). Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP.     

Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA^high, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA^high at higher risk of progression and death.     

Association of Nicotinamide Phosphoribosyltransferase (NAMPT) Gene Polymorphisms and of Serum NAMPT Levels with Dilated Cardiomyopathy in a Chinese Population

Nicotinamide phosphoribosyltransferase (NAMPT) has crucial roles for myocardial development, cardiomyocyte energy metabolism and cell death/survival by regulating NAD⁺-dependent sirtuin-1 (SIRT1) deacetylase. This study aimed to determine if the single nucleotide polymorphisms (SNPs) of the NAMPT gene may affect the susceptibility and prognosis for patients with dilated cardiomyopathy (DCM) and to describe the association of serum NAMPT levels with clinical features of DCM. Three SNPs (rs61330082, rs2505568, and rs9034) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in a case-control study of 394 DCM patients and 395 controls from China. Serum NAMPT levels were measured by enzyme-linked immunosorbent assay kits. The homozygote for the minor allele at rs2505568 and rs9034 could not be detected in this study. Rs9034 T allele and CT genotype were associated with increased DCM risk (OR: 1.63, 95% CI = 1.16–2.27, p = 0.005 and OR: 1.72, 95% CI = 1.20–2.50, p = 0.0027, respectively). Nominally significant decreased DCM risk was found to be associated with the A allele and AT genotype of rs2505568 (OR: 0.48, 95% CI = 0.35–0.67, p < 0.0001 and OR: 0.44, 95% CI = 0.31–0.62, p < 0.0001, respectively), but it should be interpreted with caution because of Hardy-Weinberg disequilibrium in the control group. Of five haplotypes constructed, TAC (rs61330082-rs2505568-rs9034) was a protective haplotype to DCM (OR: 0.22, 95% CI = 0.13–0.39, p = 1.84 × 10⁻⁸). The Cox multivariate survival analysis indicated that the rs9034 CT genotype (hazard ratio (HR): 0.59, 95% CI = 0.37–0.96, p = 0.03) was an independently multivariate predictor for longer overall survival in DCM patients. Serum NAMPT levels were significantly higher in the DCM group than controls (p < 0.0001) and gradually increased with the increase of New York Heart Association grade in DCM patients. However, there was a lack of association of the three SNPs with serum NAMPT levels. Spearman correlation test revealed that the NAMPT level was positively associated with brain natriuretic peptide (r = 0.56, p = 0.001), left ventricular end-diastolic diameter (r = 0.293, p = 0.011) and left ventricular end-diastolic volume (r = 0.294, p = 0.011). Our study suggested that NAMPT may play an important role in the development of DCM.     

Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient collective suffering from pre-diabetes or undiagnosed diabetes with its’ known adverse consequences, especially in the long-term. Hyperglycemia in sepsis might be considered as adaptive survival mechanism to hypo-perfusion and consecutive lack of glucose in peripheral cells. AMI patients with hyperglycemic derailment during an ICU-stay should be closely followed-up and extensively screened for diabetes to improve patients’ outcome.     

MMP-7 and fcDNA Serum Levels in Early NSCLC and Idiopathic Interstitial Pneumonia: Preliminary Study

A non-invasive test to facilitate the diagnosis of non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) is still not available and represents an important goal. Forty-eight patients with stage I NSCLC, 45 with IPF, 30 with other idiopathic interstitial pneumonias (IIPs) including idiopathic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (HP), 35 with diffuse non-malignant disease and 30 healthy donors were enrolled onto the study. Free circulating (fc)DNA and MMP-7 levels were evaluated by Real Time PCR and ELISA, respectively. Median fcDNA levels were similar in NSCLC (127 ng/mL, range 23.6–345 ng/mL) and IPF (106 ng/mL, range 22–224 ng/mL) patients, and significantly lower in IIPs patients, in individuals with other diseases and in healthy donors (p < 0.05). Conversely, median MMP-7 values were significantly higher in IPF patients (9.10 ng/mL, range 3.88–19.72 ng/mL) than in those with NSCLC (6.31 ng/mL, range 3.38–16.36 ng/mL; p < 0.0001), NSIP (6.50 ng/mL, range 1.50–22.47 ng/mL; p = 0.007), other diseases (5.41 ng/mL, range 1.78–15.91, p < 0.0001) or healthy donors (4.35 ng/mL, range 2.45–7.23; p < 0.0001). Serum MMP-7 levels seem to be capable of distinguishing IPF patients from those with any other lung disease. fcDNA levels were similar in NSCLC and IPF patients, confirming its potential role as a biomarker, albeit non-specific, for the differential diagnosis of NSCLC.     

Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis

Elevation in C-reactive protein (CRP) levels have been shown in patients with aortic valve stenosis (AS). Minor allele of the CRP gene (CRP) rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96) vs. 1.68 (0.98–2.90) mg/L, p < 0.001) and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01) compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.     

Significant Decline in Galactomannan Signal during Storage of Clinical Serum Samples

Galactomannan (GM) is widely used for detection of invasive aspergillosis in high-risk haemato-oncology patients. Recent publications have reported a lack of repeatability of GM detection. The objective of this retrospective study was to assess the repeatability of GM levels during storage of clinical samples. In a GM screening strategy, positive sera were repeat tested as per manufacturer’s recommendations. Short-term (ST) storage of samples was at +4 °C while long-term (LT) storage was at −80 °C. Bronchoalveolar (BAL) fluid was also repeating tested after ST storage and LT storage. Wilcoxon Signed Ranks Test was employed to assess the repeatability of GM levels. In a subset of 14 GM positive sera, repeat testing was performed on both the original serum and ethylenediaminetetraacetic acid (EDTA) pre-treated sample. There was a significant reduction in GM signals on repeat testing following ST storage (median GM index: 0.65 vs. 0.19; p < 0.001) and LT storage (median GM index: 0.56 vs. 0.10; p < 0.001) of serum samples. Of samples that were initially GM positive, an average GM index reduction of 50% was seen, with approximately two-thirds becoming GM negative on repeat testing of the same sample. In contrast, GM signal loss was not seen on repeat testing of BAL fluid following ST or LT storage. When GM positive serum samples were repeat tested using EDTA pre-treated serum from the first step of the testing protocol, all samples remained GM positive. In contrast, when the same samples were repeat tested from the original collected serum, 9 samples (64%) became GM negative. The significant reduction in GM signals during ST and LT storage of serum samples has implications for clinical management. Although the reasons for GM decline are unknown, they occur prior to the EDTA pre-treatment stage, indicating that the time from phlebotomy to testing should be minimized. BAL fluid GM index values remain stable.