Grey-Scale Analysis Improves the Ultrasonographic Evaluation of Thyroid Nodules

Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03–0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4–74.5%), specificity of 72.0% (67.8–75.9%), positive likelihood ratio (LR) of 2.023 (1.434–2.852), and negative LR of 0.602 (0.398–0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59–7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69–105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7–90.1%), specificity of 46.8% (42.3–51.4%), positive LR of 1.442 (1.164–1.786), and negative LR of 0.498 (0.259–0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure.     

Genetic Polymorphisms of Functional Candidate Genes and Recurrent Acute Otitis Media With or Without Tympanic Membrane Perforation

Evaluation of the genetic contribution to the development of recurrent acute otitis media (rAOM) remains challenging. This study aimed to evaluate the potential association between single nucleotide polymorphisms (SNPs) in selected genes and rAOM and to analyze whether genetic variations might predispose to the development of complicated recurrent cases, such as those with tympanic membrane perforation (TMP).A total of 33 candidate genes and 47 SNPs were genotyped in 200 children with rAOM (116 with a history of TMP) and in 200 healthy controls.INFγ rs 12369470CT was significantly less common in the children with rAOM than in healthy controls (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.25–1, P = 0.04). Although not significant, interleukin (IL)-1β rs 1143627G and toll-like receptor (TLR)-4 rs2737191AG were less frequently detected in the children with rAOM than in controls. The opposite was true for IL-8 rs2227306CT, which was found more frequently in the children with rAOM than in healthy controls. The IL-10 rs1800896TC SNP and the IL-1α rs6746923A and AG SNPs were significantly more and less common, respectively, among children without a history of TMP than among those who suffered from this complication (OR 2.17, 95% CI 1.09–4.41, P = 0.02, and OR 0.42, 95% CI 0.21–0.84, P = 0.01).This study is the first report suggesting an association between variants in genes encoding for factors of innate or adaptive immunity and the occurrence of rAOM with or without TMP, which confirms the role of genetics in conditioning susceptibility to AOM.     

Interaction of a new low molecular weight heparin (OP/LMWH) with human platelets

In vitro platelet proaggregating effect of unfractionated heparin (H) and OP/LMWH were studied with human platelets. OP/LMWH produced a significant less potentiation of ADP and PAF induced aggregation and slightly counteracted the antiaggregating effect of PGI2, in comparison with H. The proaggregating effect of both heparins was neutralized by equal contemporaneous amount of protamine sulfate.     

Structural features of dermatan sulfates and their relationship to anticoagulant and antithrombotic activities

Dermatan sulfate is a polydisperse, microheterogeneous sufated copolymer of N-acetyl-D-galactopyranose and idopyranosyluronic acid that is currently under clinical investigation as a new antithrombotic agent. The structure and activity of two pairs of dermatan sulfates, isolated from bovine and porcine mucosa, were studied. One dermatan sulfate from each species demonstrated high in vivo antithrombotic activity in the rat vena cava assay. The in vitro anticoagulant activity of each dermatan sulfate was determined using activated partial thromboplastin time (APTT), thrombin time (TT) (5 units), calcium thrombin time (CaTT) (5 units), Heptest, anti-factor Xa and anti-factor IIa antithrombin assays and heparin cofactor II amidolytic assays. The coagulation-based assays gave the best correlation to in vivo antithrombotic activity. The physical and chemical properties of each dermatan sulfate were determined using 1H-NMR and 13C-NMR spectroscopy, molecular weight determination, potentiometric titration, chemical degradative analysis, chondroitin lyase degradative analysis and oligosaccharide mapping. These analyses indicated that the major difference between dermatan sulfates from a particular species having high and low in vivo antithrombotic activity was their iduronic acid content. The relation between increased iduronic acid content and increased in vivo antithrombotic activity may be the result of the conformational flexibility of this residue.     

Effects of iloprost, either administered for 1 week or 4 weeks, on systemic hemodynamics, peripheral blood flow, and exercise tolerance in patients with peripheral occlusive arterial disease at leriche-fontaine stage III

Twenty patients, 15 males and 5 females, aged 50–71 years, with peripheral obstructive arterial disease at Fontaine stage III and requiring hospitalization, were randomized to two different iloprost treatment schedules: iloprost i.v. infusion, up to 2 ng/kg/minute for 6 hours/day for 28 days (Group A) or iloprost i.v. infusion, up to 1.5 ng/kg/minute, for 16 hours/day for 7 days (Group B). At baseline, after 7 days (end of treatment, Group B only) and after 28 days (end of study) the following measurements were done: blood pressure and heart rate, ankle/arm pressure index, first flow, peak flow, time to regression (by means of mercury strain-gauge plethysmography), stroke volume, cardiac output, ejection fraction (by means of 2D-echocardiography and echo-Doppler), exercise tolerance (by means of treadmill test), and rest pain (by means of visual analogue scale). Both treatment schedules resulted in significant improvement in plethysmographic parameters and exercise tolerance (both maximal and pain free) with concomitant reduction in rest pain. These effects were long lasting as evident by the results observed in Group B where the absolute data after 3 weeks of drug withdrawal were superimposable to those of Group A. On the contrary, only mild effects were evident on systemic hemodynamics, which tended to wane off as the infusion was stopped. From the results of this pilot study it is possible to conclude that treatment with iloprost at lower dosage (up to 1.5 ng/kg/minute) for 16 hour/day for 7 days, in patients at Fontaine stage III, seems to result in the same therapeutic benefits of the currently used schedule (up to 2 ng/kg/minute for 6 hour/day for 28 days). If confirmed by larger clinical experience, these data have clear implication in terms of patient comfort and cost containment.     

Indexed effective orifice area after mechanical aortic valve replacement does not affect left ventricular mass regression in elderly.

OBJECTIVE: After aortic valve replacement, the effects of a small functional prosthesis on the extent and pattern of regression of left ventricular hypertrophy and on clinical outcomes may be less significant in older patients with low cardiac output requirements. The objective of this study was therefore to determine whether patient-prosthesis mismatch affects left ventricular mass regression in the elderly. METHODS: The population studied was made up of 88 patients over 65 years of age with pure aortic stenosis who underwent mechanical aortic valve replacement. The effective orifice area index was calculated for each patient on the basis of the projected prosthesis in vivo effective orifice area. It was considered a continuous variable and influence of its entire range of values on the extent of left ventricular mass regression was analyzed in a multivariate prediction model. RESULTS: Even though, in the group with prosthesis-patient mismatch there was a trend for lower postoperative left ventricular mass index (115+/-24 g/m(2) vs 102+/-27 g/m(2), p=0.24) and postoperative peak trans-prosthetic gradients (32+/-9.8 mmHg vs 28.9+/-7.79 mmHg, p=0.35) these differences were not statistically significant. The prevalence of residual left ventricular hypertrophy at follow-up was 50% in the group with patient-prosthesis mismatch and 50% in the group without patient-prosthesis mismatch (p=0.83). In multivariate analysis the only factors associated with indexed left ventricular mass were the follow-up time (p=0.015, r(2)=0.22) and preoperative indexed left ventricular mass (p=0.0012, r(2)=0.11). CONCLUSIONS: The major finding of our study is that patient-prosthesis mismatch does not affect left ventricular mass regression in patients older than 65 with pure aortic stenosis who underwent mechanical aortic valve replacement. In older patients with low cardiac output requirements, even a small change in the valve effective orifice area after aortic valve replacement with modern efficient mechanical prosthesis, will result in a marked reduction of pressure gradient and this will be associated with a significant regression of left ventricular mass.     

Wine and resveratrol: mechanisms of cancer prevention?

Low alcohol consumption seems to decrease total mortality and to have beneficial properties on cardiovascular disease; data for cancer are still inconclusive. There is evidence that wine consumption decreases the risk of cancer at several sites, including cancer of upper digestive tract, lung, colon, basal cell carcinoma, and non-Hodgkin lymphoma. The presence of resveratrol, a polyphenol specifically present in red wine, may contribute to these cancer preventive effects. Resveratrol in fact inhibits the metabolic activation of carcinogens, has antioxidant and anti-inflammatory properties, decreases cell proliferation and induces apoptosis. Data on the availability of resveratrol in vivo are however still lacking. Although regular consumption of one or two glasses of wine seems reasonably safe from the health point of view, a recommendation to the general population for low wine consumption is not justified.