Myocardial perfusion imaging with 99 mTc - tetrofosmin SPECT in breast cancer patients that received postoperative radiotherapy: a case-control study

<p>Abstract</p> <p>Purpose</p> <p>To evaluate the cardiac toxicity of radiotherapy (RT) in breast cancer (BC) patients employing myocardial perfusion imaging (MPI) with Tc-99 m Tetrofosmin - single photon emission computer tomography (T-SPECT).</p> <p>Materials and methods</p> <p>We studied 46 BC female patients (28 patients with left and 18 patients with right BC) treated with postoperative RT compared to a control group of 85 age-matched females. The median time of RT to SPECT was 40 months (6-263).</p> <p>Results</p> <p>Abnormalities in the summed stress score (SSS) were found in 54% of left BC patients, 44.4% of right BC patients, and 32.9% of controls. In left BC patients there were significantly more SSS abnormalities compared to controls (4.0 ± 3.5 vs 2.6 ± 2.0, p = 0.05) and possible trend of increased abnormalities of right BC patients (3.7 ± 3.0 vs 2.6 ± 2.0, p = 0.14). Multiple regression analysis showed more abnormalities in the MPI of left BC patients compared to controls (SSS, p = 0.0001); Marginal toxicity was also noted in right BC patients (SSS, p = 0.045). No additional toxicity was found in patients that received adjuvant cardiotoxic chemotherapy. All T-SPECT abnormalities were clinically silent.</p> <p>Conclusion</p> <p>The study suggests that radiation therapy to BC patients result in MPI abnormalities but without apparent clinical consequences.</p

Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1–infected individuals to a mean of 49.4 ± SD 12.9% of CD8+ T cells expressing Tim-3 in HIV-1–infected chronic progressors versus 28.5 ± 6.8% in HIV-1–uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1–infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1–specific CD8+ T cells. Tim-3–expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1–specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1–associated T cell dysfunction

Evaluation of Intereye Corneal Asymmetry in Patients with Keratoconus. A Scheimpflug Imaging Study

Purpose: To assess the correlation between keratoconus severity and intereye asymmetry of pachymetric data and posterior elevation values and to evaluate their combined accuracy in discriminating normal corneas from those with keratoconus. Methods: This study included 97 patients: 65 subjects with bilateral normal corneas (NC) and 32 with keratoconus (KC). Central corneal thickness (CCT), thinnest corneal thickness (ThCT) and posterior elevation (PE) at the thinnest point of the cornea were measured in both eyes using Scheimpflug imaging. Intereye asymmetry and its correlation with keratoconus severity were calculated for each variable. The area under the receiver operating characteristic curve (AUROC) was used to compare predictive accuracy of different variables for keratoconus. Results: In normal eyes, intereye differences were significantly lower compared with the keratoconus eyes (p<0.001, for CCT, ThCT and PE). There was a significant exponential correlation between disease severity and intereye asymmetry of steep keratometry (r(2) = 0.55, p<0.001), CCT (r(2) = 0.39, p<0.001), ThCT (r(2) = 0.48, p<0.001) and PE (r(2) = 0.64, p<0.001). After adjustment for keratoconus severity, asymmetry in thinnest pachymetry proved to be the best parameter to characterize intereye corneal asymmetry in keratoconus. This variable had high accuracy and significantly better discriminating ability (AUROC: 0.99) for KC than posterior elevation (AUROC: 0.96), ThCT (AUROC: 0.94) or CCT (AUROC: 0.92) alone. Conclusions: There is an increased intereye asymmetry in keratometry, pachymetry and posterior corneal elevation values in keratoconic patients compared to subjects with normal corneas. Keratoconus patients with more severe disease are also more asymmetric in their disease status which should be taken into account during clinical care

Solubilization of Proteins in 2DE: An Outline

Protein solubilization for two-dimensional electrophoresis (2DE) has to break molecular interactions to separate the biological contents of the material of interest into isolated and intact polypeptides. This must be carried out in conditions compatible with the first dimension of 2DE, namely isoelectric focusing. In addition, the extraction process must enable easy removal of any nonprotein component interfering with the isoelectric focusing. The constraints brought in this process by the peculiar features of isoelectric focusing are discussed, as well as their consequences in terms of possible solutions and limits for the solubilization process

A multi-region assessment of population rates of cardiac catheterization and yield of high-risk coronary artery disease

<p>Abstract</p> <p>Background</p> <p>There is variation in cardiac catheterization utilization across jurisdictions. Previous work from Alberta, Canada, showed no evidence of a plateau in the yield of high-risk disease at cardiac catheterization rates as high as 600 per 100,000 population suggesting that the optimal rate is higher. This work aims 1) To determine if a previously demonstrated linear relationship between the yield of high-risk coronary disease and cardiac catheterization rates persists with contemporary data and 2) to explore whether the linear relationship exists in other jurisdictions.</p> <p>Methods</p> <p>Detailed clinical information on all patients undergoing cardiac catheterization in 3 Canadian provinces was available through the Alberta Provincial Project for Outcomes Assessment in Coronary Heart (APPROACH) disease and partner initiatives in British Columbia and Nova Scotia. Population rates of catheterization and high-risk coronary disease detection for each health region in these three provinces, and age-adjusted rates produced using direct standardization. A mixed effects regression analysis was performed to assess the relationship between catheterization rate and high-risk coronary disease detection.</p> <p>Results</p> <p>In the contemporary Alberta data, we found a linear relationship between the population catheterization rate and the high-risk yield. Although the yield was slightly less in time period 2 (2002-2006) than in time period 1(1995-2001), there was no statistical evidence of a plateau. The linear relationship between catheterization rate and high-risk yield was similarly demonstrated in British Columbia and Nova Scotia and appears to extend, without a plateau in yield, to rates over 800 procedures per 100,000 population.</p> <p>Conclusions</p> <p>Our study demonstrates a consistent finding, over time and across jurisdictions, of linearly increasing detection of high-risk CAD as population rates of cardiac catheterization increase. This internationally-relevant finding can inform country-level planning of invasive cardiac care services.</p

Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapy

Background Adjuvant radiotherapy (RT) for left-sided breast cancer increases cardiac morbidity and mortality. For the heart, no safe radiation threshold has been established. Troponin T is a sensitive marker of myocardial damage. Our aim was to evaluate the effect of left-sided breast cancer RT on serum high sensitivity troponin T (hscTnT) levels and its association with cardiac radiation doses and echocardiographic parameters. Methods A total of 58 patients with an early stage, left-sided breast cancer or ductal carcinoma in situ (DCIS) who received adjuvant breast RT without prior chemotherapy were included in this prospective, non-randomized study. Serum samples were taken before, during and after RT. An increase of hscTnT >30 % was predefined as significant. A comprehensive 2D echocardiograph and electrocardiogram (ECG) were performed before and after RT. Dose-volume histograms (DVHs) were generated for different cardiac structures. Results The hscTnT increased during RT from baseline in 12/58 patients (21 %). Patients with increased hscTnT values (group A, N = 12) had significantly higher radiation doses for the whole heart (p = 0.02) and left ventricle (p = 0.03) than patients without hscTnT increase (group B, N = 46). For the left anterior descending artery (LAD), differences between groups A and B were found in volumes receiving 15 Gy (p = 0.03) and 20 Gy (p = 0.03) Furthermore, after RT, the interventricular septum thickened (p = 0.01), and the deceleration time was prolonged (p = 0.008) more in group A than in group B. Conclusions The increase in hscTnT level during adjuvant RT was positively associated with the cardiac radiation doses for the whole heart and LV in chemotherapy-naive breast cancer patients. Whether these acute subclinical changes increase the risk of excessive long-term cardiovascular morbidity or mortality, will be addressed in the follow-up of our patients.BioMed Central open acces

Consensus Report : 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals

Tobacco use has been identified as a major risk factor for oral disorders such as cancer and periodontal disease. Tobacco use cessation (TUC) is associated with the potential for reversal of precancer, enhanced outcomes following periodontal treatment, and better periodontal status compared to patients who continue to smoke. Consequently, helping tobacco users to quit has become a part of both the responsibility of oral health professionals and the general practice of dentistry. TUC should consist of behavioural support, and if accompanied by pharmacotherapy, is more likely to be successful. It is widely accepted that appropriate compensation of TUC counselling would give oral health professionals greater incentives to provide these measures. Therefore, TUC-related compensation should be made accessible to all dental professionals and be in appropriate relation to other therapeutic interventions. International and national associations for oral health professionals are urged to act as advocates to promote population, community and individual initiatives in support of tobacco use prevention and cessation (TUPAC) counselling, including integration in undergraduate and graduate dental curricula. In order to facilitate the adoption of TUPAC strategies by oral health professionals, we propose a level of care model which includes 1) basic care: brief interventions for all patients in the dental practice to identify tobacco users, assess readiness to quit, and request permission to re-address at a subsequent visit, 2) intermediate care: interventions consisting of (brief) motivational interviewing sessions to build on readiness to quit, enlist resources to support change, and to include cessation medications, and 3) advanced care: intensive interventions to develop a detailed quit plan including the use of suitable pharmacotherapy. To ensure that the delivery of effective TUC becomes part of standard care, continuing education courses and updates should be implemented and offered to all oral health professionals on a regular basis