Validation of the VE1 immunostain for the BRAF V600E mutation in melanoma

BACKGROUND: BRAF mutation status, and therefore eligibility for BRAF inhibitors, is currently determined by sequencing methods. We assessed the validity of VE1, a monoclonal antibody against the BRAF V600E mutant protein, in the detection of mutant BRAF V600E melanomas as classified by DNA pyrosequencing. METHODS: The cases were 76 metastatic melanoma patients with only one known primary melanoma who had had BRAF codon 600 pyrosequencing of either their primary (n = 19), metastatic (n = 57) melanoma, or both (n = 17). All melanomas (n = 93) were immunostained with the BRAF VE1 antibody using a red detection system. The staining intensity of these specimens was scored from 0 to 3+ by a dermatopathologist. Scores of 0 and 1+ were considered as negative staining while scores of 2+ and 3+ were considered positive. RESULTS: The VE1 antibody showed a sensitivity of 85% and a specificity of 100% as compared to DNA pyrosequencing results. There was 100% concordance between VE1 immunostaining of primary and metastatic melanomas from the same patient. V600K, V600Q, and V600R BRAF melanomas did not positively stain with VE1. CONCLUSIONS: This hospital-based study finds high sensitivity and specificity for the BRAF VE1 immunostain in comparison to pyrosequencing in detection of BRAF V600E in melanomas

The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival

Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined

IL2 Inducible T-cell Kinase, a Novel Therapeutic Target in Melanoma

Interleukin-2 inducible T-cell kinase (ITK) promoter CpG sites are hypomethylated in melanomas compared to nevi. The expression of ITK in melanomas, however, has not been established and requires elucidation

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Discrimination of the toxigenic dinoflagellate species Alexandrium tamarense and Alexandrium ostenfeldii in co-occurring natural populations from Scottish coastal waters

Blooms of the toxic dinoflagellate Alexandrium tamarense (Lebour) Balech, a known producer of potent neurotoxins associated with paralytic shellfish poisoning (PSP), are common annual events along the Scottish east coast. The co-occurrence of a second Alexandrium species, A. ostenfeldii (Paulsen) Balech & Tangen is reported in this study from waters of the Scottish east coast. The latter species has been suspected to be an alternative source of PSP toxins in northern Europe. Recent identification of toxic macrocyclic imines known as spirolides in A. ostenfeldii indicates a potential new challenge for monitoring toxic Alexandrium species and their respective toxins in natural populations. In mixed phytoplankton assemblages, Alexandrium species are dicult to discriminate accurately by conventional light microscopy. Species-specific rRNA probes based upon 18S and 28S ribosomal DNA sequences were developed for A. ostenfeldii and tested by dot-blot and fluorescence in situ hybridization (FISH) techniques. Hybridization patterns of A. ostenfeldii probes for cultured Alexandrium isolates, and cells from field populations from the Scottish east coast, were compared with those of rDNA probes for A. tamarense and a universal dinoflagellate probe. Alexandrium cell numbers in field samples determined by whole-cell in situ hybridization were much lower than those determined by optical microscopy with the Utermöhl method involving sedimentation chambers, but the results were highly correlated (e.g. r2=0.94; n=6 for A. tamarense). Determination of spirolides and PSP toxins by instrumental analysis on board ship demonstrated the presence of both toxi

G017 Factors associated with the induction of antidromic tachycardia in the wolff-parkinson-white syndrome

Atrioventricular reentrant tachycardia (AVRT) is the most frequent inducible tachycardia in patients with a Wolff-Parkinson-White syndrome (WPW). The incidence and the causes of the induction of antidromic tachycardia (ATD) are unknown. The purpose of the study was to determine the data of patients with a WPW and with inducible ATD.Methods605 patients had a WPW and tachycardias (n=312) or syncope (n=85); other patients were asymptomatic (n=208). Electrophysiological study (EPS) was systematic. In control state (CS), the higher rate conducted through accessory pathway (AP) was measured; programmed atrial stimulation with 1, 2 extrastimuli was performed to induce a tachycardia. Isoproterenol (0.02 to 1μg. min-1) was infused and the protocol was repeated.ResultsATD was induced in 44 patients (7 %) (group I). Their data were compared to those of remaining patients (group II). Group I differed from group II by the following data: Female sex was less frequent in group I (29.5 %) than in group II (47 %); AP was more frequently left sided in group I (54.5 %) than in group II (38 %) (p<0.05). AVRT was induced less frequently in group I (34 %) than in group II (57 %) (p<0.01); maximal rate conducted through AP was higher in group I (215±52b/min) than in group II (189±61) in control state, and after isoproterenol (281±57 in group I vs 236±61 in group II) (p<0.001). Some data were similar: Age was not different in group I (33.5±20 years) and II (34.5±17); the indications of EPS were similar (syncope, reentrant tachycardia, atrial fibrillation (AF) or asymptomatic WPW were the reasons for 16 %, 43 %, 11 % and 25 % of group I patients and 14 %, 46 %, 5.5 % and 35 % of group II patients); posteroseptal and right AP locations were similar in both groups; AF was induced as frequently in group I (27 %) as in group II (23 %).Conclusionsantidromic tachycardia was induced more frequently in men than in women, with a left lateral AP which conducted more rapidly than in other patients