Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin lymphoma (HL) secrete factors that interact with inflammatory background cells and may serve as biomarkers for disease activity. To detect new proteins related to pathogenesis, we analyzed the secretome of HRS cells. Proteins in cell culture supernatant of 4 HL cell lines were identified using 1DGE followed by in-gel trypsin digestion and LC-MS/MS. In total, 1290 proteins, including 368 secreted proteins, were identified. Functional grouping of secreted proteins revealed 37 proteins involved in immune response. Sixteen of the 37 proteins (ie, ALCAM, Cathepsin C, Cathepsin S, CD100, CD150, CD26, CD44, CD63, CD71, Fractal-kine, IL1R2, IL25, IP-10, MIF, RANTES, and TARC) were validated in HL cell lines and patient material using immunohistochemistry and/or ELISA. Expression of all 16 proteins was confirmed in HL cell lines, and 15 were also confirmed in HL tissues. Seven proteins (ALCAM, cathepsin S, CD26, CD44, IL1R2, MIF, and TARC) revealed significantly elevated levels in patient plasma compared with healthy controls. Proteomics analyses of HL cell line supernatant allowed detection of new secreted proteins, which may add to our insights in the interaction between HRS cells and infiltrating lymphocytes and in some instances might serve as biomarkers.     

A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism

The (A/G)-308 polymorphism of the tumor necrosis factor alpha gene (TNF) is associated with age-related diseases, but its influence on longevity is controversial. We genotyped for this polymorphism 747 Italian volunteers (401 women and 346 men, age 19-110 years). By applying a genetic-demographic (GD) approach we found that, in men, the survival function of allele A carriers is lower than that of noncarriers at all the ages (p =.044). After defining (by exploiting again demographic information) three age classes, we found that the frequency of men carrying the A allele decreases with age (p =.019), thus confirming the GD analysis results. The same analyses gave negative results in women. Therefore, allele A has a detrimental effect on life expectancy, and this effect is specific to men. A haplotype analysis carried out in men by screening the TNFa, TNFc, and TNFe microsatellite polymorphisms (spanning about 20 kb) confirmed the association of the TNF region with life expectancy.     

A Look at the Current Reimbursement Environment for Continuous Glucose Monitoring (CGM): Understanding the Fundamentals

As reimbursement continues to decline for diabetes management technologies and practice overhead continues to rise, it is becoming increasingly important to understand the current reimbursement environment for new technological innovations in diabetes care. The current environment demands a strong partnership among providers, key stakeholder groups, and industry to advocate for favorable coding, coverage, and payment of these new advancements, in order to improve accessibility to the patient. This article describes trends in the current reimbursement environment for continuous glucose monitoring and provides recommendations on how to maneuver through the intricacies of coding and coverage related to this emerging category of glucose monitoring.     

Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human alcoholic cirrhosis

BACKGROUND/AIMS: The liver plays a prominent role in the metabolism of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase. This study was designed to determine whether plasma levels of ADMA and NO production are altered in patients with compensated and decompensated alcoholic cirrhosis. METHODS: Plasma levels of l-arginine, ADMA, symmetric dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls. RESULTS: ADMA and NOx concentrations in decompensated cirrhosis were higher than in the compensated group and control group (ADMA: 1.12+/-0.08 vs. 0.58+/-0.05 and 0.58+/-0.07micromol/l, respectively; P<0.05; NOx 97.90+/-10.27 vs. 37.42+/-3.91 and 40.43+/-5.30micromol/l, respectively; P<0.05). There was a positive correlation between the clinical score of the patients and concentrations of ADMA (r(2)=0.547, P<0.01) and NOx (r(2)=0.689, P<0.01). SDMA and l-arginine levels were not significantly different between the three groups. CONCLUSIONS: The results suggest that hepatocellular damage is a main determinant of elevated ADMA concentration in advanced alcoholic cirrhosis. By inhibiting NO release from vascular endothelium, ADMA might oppose the peripheral vasodilation caused by excessive NO production in severe cirrhosis.     

Cirugía de las metástasis en la glándula suprarrenal: resultados de una serie de 35 pacientes

IntroductionThe objectives of this study are to present the results of adrenalectomies due to metastasis, and to analyse the prognostic factors that may help to predict long-term survival in this patient group.Patients and methodsA retrospective study was conducted on 35 patients who underwent adrenalectomy for metastases in the Hospital de Cruces from 1996 to January 2010. The survival analysis was performed using the Kaplan and Meier method.ResultsNon-small cell lung cancer (NSCLC) was the most frequent primary tumour, with 18 cases. In 15 patients the diagnosis of adrenal metastasis was synchronous with the primary tumour, and in 20 cases it was metachronous. Only 7 patients survived without disease for 12, 22, 26, 58, 60, 65 and 120 months after the adrenalectomy. The disease free survival at 5 years was 16% in the whole series, and 27% in the NSCLC sub-group. None of the prognostic factors evaluated (size greater than 4.5 cm, cell type, differentiation grade, chemotherapy, surgical technique, disease free interval) was statistically significant in the overall survival, either in the general series or in the sub-group of patients with NSCLC. However, in the general series with tumour recurrence, the difference in survival between metachronous and synchronous metastasis was statistically significant (P=.05), in favour of the former.ConclusionsAdrenalectomy improves the expected survival particularly in patients with NSCLC. Patients with metachronous metastases do not have a higher rate of disease free survival at 5 years than those with synchronous metastases, although they do have a longer survival with the disease. When there is tumour recurrence, it is usually early.     

HELLP syndrome with severe liver dysfunction: a presentation of three cases

HELLP syndrome (HS) occurs in 0.5-0.9% of pregnant women. According to the Tennessee criteria, it is characterised by haemolytic anaemia, thrombopenia and multi-organ dysfunction. The purpose of this article is to present the cases of four pregnant women diagnosed with HS with severe liver involvement. PATIENTS AND METHOD: We present the cases of 4 pregnant women of 24, 27, 28 and 36 weeks gestation, respectively. Pregnancy was terminated by urgent Caesarean section in all 4 cases. The first case required a right hepatectomy, with a good post-operative outcome; the second patient developed fulminant liver failure, dying due to multi-organ failure while waiting for a liver transplant. The third patient progressed satisfactorily with conservative medical treatment. The fourth patient required two livers transplants, being discharged from hospital three months later. CONCLUSIONS: When faced with the clinical suspicion of a HS it is essential to rule out a liver haematoma, since the treatment of choice depends on its clinical-radiological severity. If there is a rupture of the haematoma, urgent surgery is essential and, in the case of severe liver failure, a liver transplant is indicated.