Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies

Although obesity is an established risk factor for several cancer types, its possible role in the aetiology of malignant melanoma remains unclear. This meta-analysis aims to examine the association between obesity and melanoma risk, exploring any tentative gender-specific associations. After the identification of eligible studies, we estimated pooled effect estimates (odds ratios and relative risks), undertook a meta-regression analysis and analysed separately risk of malignant melanoma among males and females in relation to body mass index (BMI) and body surface area (BSA). Out of the 21 eligible articles, 11 used a case–control design encompassing 4460 cases/6342 controls; 10 used a cohort design whose total size comprised 7895 incident cases/6,368,671 subjects. Among males, the pooled effect estimate was 1.31 (95% confidence interval (CI): 1.18–1.45) for overweight and 1.31 (95% CI: 1.19–1.44) for obese. Meta-regression revealed no significant slope, most probably due to the underlying plateau in effect estimates. Among females, no significant association was documented; the pooled effect estimate for overweight and obese subjects was 0.98 (95% CI: 0.92–1.05) and 0.99 (95% CI: 0.83–1.18), respectively. Noticeably, there was evidence for confounding between sunlight exposure and obesity in females. All results were reproducible upon analyses on BSA. In conclusion, overweight and obesity are associated with increased risk of malignant melanoma among males. Meticulous assessment of sunlight exposure is needed especially in women, since self limited public sun exposure may be prevalent among overweight or obese females. Higher-order associations between BMI and melanoma risk should be addressed and examined by the future studies.     

Efficacy of Colchicine in the Treatment of Mesenteric Panniculitis in a Young Patient

Mesenteric panniculitis (MP) is a rare inflammatory and fibrotic disease of the mesentery of unknown etiology. It has various clinical and radiological manifestations, posing a diagnostic challenge for clinicians. Its diagnosis is indicated via radiologic imaging and is usually confirmed via peritoneal biopsies. We describe a case of a patient with histopathologically proven MP, in which steroid dependence was successfully managed with colchicine.     

Model selection based on combined penalties for biomarker identification

The growing role of targeted medicine has led to an increased focus on the development of actionable biomarkers. Current penalized selection methods that are used to identify biomarker panels for classification in high-dimensional data, however, often result in highly complex panels that need careful pruning for practical use. In the framework of regularization methods, a penalty that is a weighted sum of the L₁ and L₀ norm has been proposed to account for the complexity of the resulting model. In practice, the limitation of this penalty is that the objective function is non-convex, non-smooth, the optimization is computationally intensive and the application to high-dimensional settings is challenging. In this paper, we propose a stepwise forward variable selection method which combines the L₀ with L₁ or L₂ norms. The penalized likelihood criterion that is used in the stepwise selection procedure results in more parsimonious models, keeping only the most relevant features. Simulation results and a real application show that our approach exhibits a comparable performance with common selection methods with respect to the prediction performance while minimizing the number of variables in the selected model resulting in a more parsimonious model as desired.     

Compound Heterozygosity for Hb Adana (HBA2: c.179G>A) and the –α3.7/αα Thalassemia Deletion in Greece: Clinical Phenotype and Genetic Counseling

Hb Adana (HBA2: c.179G>A) is found worldwide but is extremely rare and carriers are asymptomatic, with red cell indices similar to α⁺-thalassemia (α⁺-thal) carriers. First line screening tests are unable to detect the unstable hemoglobin (Hb). Coinheritance with the α-thal (–α^3.7) deletion is herein presented and the challenges involving genetic counseling of couples carrying the mutations are discussed.     

Correlation between myocardial enzyme serum levels and markers of inflammation with severity of coronary artery disease and Gensini score: A hospital-based,prospective study in Greek patients

Background

Our objective was to associate serum levels of myocardial enzymes and inflammatory biomarkers with severity of coronary artery disease (CAD).

Patients and methods

123 patients participated in our study, including 65 cases of acute myocardial infarction (MI), 27 cases of newly diagnosed CAD – without MI – and 31 controls. In all subjects, myocardial serum enzyme levels (creatine phosphokinase, aspartate aminotransferase, lactate dehydrogenase) and inflammatory indices (C-reactive protein, fibrinogen, white blood cells, and erythrocyte sedimentation rate) were measured. Patients were all submitted to coronary angiography and CAD severity was evaluated by Gensini score.

Results

Significant differences concerning enzyme serum levels and inflammatory indices were found to exist between the three study groups, being highest among patients with acute MI (p < 0.001). A significant association was demonstrated between Gensini score and serum enzyme levels as well as inflammatory biomarkers.

Conclusions

Our findings suggest that serum levels of myocardial enzymes and inflammatory indices correlate with CAD severity in Greek patients.     

Impaired generation of bone marrow CD34-derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a stem cell disorder characterized by ineffective haematopoiesis and blood cytopenias. The present study investigated the potential of bone marrow CD34(+) progenitors in MDS patients to proliferate and differentiate into dendritic cells (DCs) in a cytokine-supplemented liquid culture system and analysed the status of blood DC subsets in these patients. CD34(+) progenitors had low potential to generate DCs in vitro, as the number of DCs obtained from one CD34(+) cell was significantly lower compared with controls (median value 0.2 vs. 4, P = 0.003). In patients, the survival and proliferation of CD34(+) cells in culture was not correlated to the degree of apoptosis. Phenotypically and functionally CD34(+)-derived DCs were similar in MDS patients and normal subjects. The percentage of both circulating DC subsets in patients was extremely diminished compared with controls (myeloid DC: 0.10 +/- 0.10% vs. 0.35 +/- 0.13%, P < 0.001; plasmacytoid DC: 0.11 +/- 0.10% vs. 0.37 +/- 0.14%, P < 0.001). In cases with the 5q deletion both CD34-derived DCs and blood DCs harboured the cytogenetic abnormality. Our results indicate that, in MDS, the production of DCs is affected by the neoplastic process resulting in ineffective 'dendritopoiesis' with low blood DC precursor numbers. This quantitative DC defect probably contributes to the poor immune response against infectious agents and to the escape of the malignant clone from immune recognition with disease progression towards acute leukaemia.     

Helicobacter pylori infection upregulates endothelial nitric oxide synthase expression and induces angiogenesis in gastric mucosa of dyspeptic patients

BACKGROUND: Helicobacter pylori (H. pylori) infection induces nitric acid (NO) overproduction through inducible NO synthase (NOS) expression, subsequent DNA damage and enhanced antiapoptosis signal transduction sequence in the human gastric mucosa, whereas its possible effect on endothelial nitric oxide synthase (eNOS) expression has not as yet been investigated. The aim of this study was to evaluate the effect of H. pylori infection in the expression of eNOS in gastric mucosa. PATIENTS AND METHODS: We prospectively studied 30 nonsmoking dyspeptic patients (12 men, 18 women, mean age 54.26+/-12.89 years). The diagnosis of H. pylori infection was based mainly on histology. The histological grading of H. pylori infection was evaluated according to the modified Sydney classification. Histological grading of eNOS expression and microvessel density as estimated by CD34 expression were determined by immunohistochemistry (degree 0-3) and correlated with H. pylori infection and histological degree of gastritis. RESULTS: Twelve patients were H. pylori-positive and 18 patients were H. pylori-negative. The two groups were matched for age (P=0.139), sex (P=0.342) and similar degree of gastritis. Intensity of eNOS and CD34 expression in the corpus and antrum were significantly correlated (P<0.001). eNOS expression was correlated with H. pylori infection in the mucosa of the body and antrum (P=0.013 and 0.037, respectively) but not with gastric inflammation and activity (P=0.848 and 0.871, respectively, for the corpus and P=0.565 and 0.793, respectively, for the antrum). H. pylori-positive patients showed higher expression of CD34-positive blood vessels in the mucosa of the antrum (P=0.048). CD34 expression was correlated with gastric inflammation and activity (P=0.03 and 0.044, respectively) in the mucosa of the antrum of H. pylori-positive patients. CONCLUSION: H. pylori infection upregulates eNOS, and induces angiogenesis, contributing to H. pylori-associated pathophysiology in gastric mucosa.