Asymptomatic cardiac disease following mediastinal irradiation

AbstractObjectivesThis study was designed to evaluate the potential benefit of screening previously irradiated patients with echocardiography.BackgroundMediastinal irradiation is known to cause cardiac disease. However, the prevalence of asymptomatic cardiac disease and the potential for intervention before symptom development are unknown.MethodsWe recruited 294 asymptomatic patients (mean age 42 ± 9 years, 49% men, mean mantle irradiation dose 43 ± 0.3 Gy) treated with at least 35 Gy to the mediastinum for Hodgkin's disease. After providing written consent, each patient underwent electrocardiography and transthoracic echocardiography.ResultsValvular disease was common and increased with time following irradiation. Patients who had received irradiation more than 20 years before evaluation had significantly more mild or greater aortic regurgitation (60% vs. 4%, p < 0.0001), moderate or greater tricuspid regurgitation (4% vs. 0%, p = 0.06), and aortic stenosis (16% vs. 0%, p = 0.0008) than those who had received irradiation within 10 years. The number needed to screen to detect one candidate for endocarditis prophylaxis was 13 (95% confidence interval [CI] 7 to 44) for patients treated within 10 years and 1.6 (95% CI 1.3 to 1.9) for those treated at least 20 years ago. Compared with the Framingham Heart Study population, mildly reduced left ventricular fractional shortening (<30%) was more common (36% vs. 3%), and age- and gender-adjusted left ventricular mass was lower (90 ± 27 g/m vs. 117 g/m) in irradiated patients.ConclusionsThere is a high prevalence of asymptomatic heart disease in general, and aortic valvular disease in particular, following mediastinal irradiation. Screening echocardiography should be considered for patients with a history of mediastinal irradiation

Randomized trial of conventional transseptal needle versus radiofrequency energy needle puncture for left atrial access (the TRAVERSE-LA study).

BackgroundTransseptal puncture is a critical step in achieving left atrial (LA) access for a variety of cardiac procedures. Although the mechanical Brockenbrough needle has historically been used for this procedure, a needle employing radiofrequency (RF) energy has more recently been approved for clinical use. We sought to investigate the comparative effectiveness of an RF versus conventional needle for transseptal LA access.Methods and resultsIn this prospective, single-blinded, controlled trial, 72 patients were randomized in a 1:1 fashion to an RF versus conventional (BRK-1) transseptal needle. In an intention-to-treat analysis, the primary outcome was time required for transseptal LA access. Secondary outcomes included failure of the assigned needle, visible plastic dilator shavings from needle introduction, and any procedural complication. The median transseptal puncture time was 68% shorter using the RF needle compared with the conventional needle (2.3 minutes [interquartile range {IQR}, 1.7 to 3.8 minutes] versus 7.3 minutes [IQR, 2.7 to 14.1 minutes], P = 0.005). Failure to achieve transseptal LA access with the assigned needle was less common using the RF versus conventional needle (0/36 [0%] versus 10/36 [27.8%], P &lt; 0.001). Plastic shavings were grossly visible after needle advancement through the dilator and sheath in 0 (0%) RF needle cases and 12 (33.3%) conventional needle cases (P &lt; 0.001). There were no differences in procedural complications (1/36 [2.8%] versus 1/36 [2.8%]).ConclusionsUse of an RF needle resulted in shorter time to transseptal LA access, less failure in achieving transseptal LA access, and fewer visible plastic shavings

Microwave Assisted Formation of Monoreactive Perfluoroalkylsilane-based Self-Assembled Monolayers

We demonstrate the use of microwave radiation as a tool to accelerate the formation of perfluoroalkylsilane based self-assembled monolayers (SAMs) on silicon oxide surfaces. Surface coverage of these SAMs of monoreactive perfluoroalkylsilanes increased in proportion to the duration over which the solutions were heated by microwave radiation.&nbsp

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8&nbsp;weeks of high-dose prednisone (&gt;30&nbsp;mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, &lt;10&nbsp;mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen

Z^* Resonances: Phenomenology and Models

We explore the phenomenology of, and models for, the Z^* resonances, the lowest of which is now well established, and called the Theta. We provide an overview of three models which have been proposed to explain its existence and/or its small width, and point out other relevant predictions, and potential problems, for each. The relation to what is known about KN scattering, including possible resonance signals in other channels, is also discussed.Comment: 29 pages, uses RevTeX4; expanded version (published form

Do Dimensions of Ethnic Identity Mediate the Association Between Perceived Ethnic Group Discrimination and Depressive Symptoms?

Ethnic group discrimination represents a notable risk factor that may contribute to mental health problems among ethnic minority college students. However, cultural resources (e.g., ethnic identity) may promote psychological adjustment in the context of group-based discriminatory experiences. In the current study, we examined the associations between perceptions of ethnic group discrimination and depressive symptoms, and explored dimensions of ethnic identity (i.e., exploration, resolution, and affirmation) as mediators of this process among 2,315 ethnic minority college students (age 18 to 30 years; 37% Black, 63% Latino). Results indicated that perceived ethnic group discrimination was associated positively with depressive symptoms among students from both ethnic groups. The relationship between perceived ethnic group discrimination and depressive symptoms was mediated by ethnic identity affirmation for Latino students, but not for Black students. Ethnic identity resolution was negatively and indirectly associated with depressive symptoms through ethnic identity affirmation for both Black and Latino students. Implications for promoting ethnic minority college students’ mental health and directions for future research are discussed

Meaning in life in emerging adulthood: a person-oriented approach

The present study investigated naturally occurring profiles based on two dimensions of meaning in life: Presence of Meaning and Search for Meaning. Cluster analysis was used to examine meaning-in-life profiles, and subsequent analyses identified different patterns in psychosocial functioning for each profile. A sample of 8,492 American emerging adults (72.5% women) from 30 colleges and universities completed measures on meaning in life, and positive and negative psychosocial functioning. Results provided support for five meaningful yet distinguishable profiles. A strong generalizability of the cluster solution was found across age, and partial generalizability was found across gender and ethnicity. Furthermore, the five profiles showed specific patterns in relation to positive and negative psychosocial functioning. Specifically, respondents with profiles high on Presence of Meaning showed the most adaptive psychosocial functioning, whereas respondents with profiles where meaning was largely absent showed maladaptive psychosocial functioning. The present study provided additional evidence for prior research concerning the complex relationship between Presence of Meaning and Search for Meaning, and their relation with psychosocial functioning. Our results offer a partial clarification of the nature of the Search for Meaning process by distinguishing between adaptive and maladaptive searching for meaning in life

Identification and Functional Analysis of Epigenetically Silenced MicroRNAs in Colorectal Cancer Cells

Abnormal microRNA (miRNA) expression has been linked to the development and progression of several human cancers, and such dysregulation can result from aberrant DNA methylation. While a small number of miRNAs is known to be regulated by DNA methylation, we postulated that such epigenetic regulation is more prevalent. By combining MBD-isolated Genome Sequencing (MiGS) to evaluate genome-wide DNA methylation patterns and microarray analysis to determine miRNA expression levels, we systematically searched for candidate miRNAs regulated by DNA methylation in colorectal cancer cell lines. We found 64 miRNAs to be robustly methylated in HCT116 cells; eighteen of them were located in imprinting regions or already reported to be regulated by DNA methylation. For the remaining 46 miRNAs, expression levels of 18 were consistent with their DNA methylation status. Finally, 8 miRNAs were up-regulated by 5-aza-2′-deoxycytidine treatment and identified to be novel miRNAs regulated by DNA methylation. Moreover, we demonstrated the functional relevance of these epigenetically silenced miRNAs by ectopically expressing select candidates, which resulted in inhibition of growth and migration of cancer cells. In addition to reporting these findings, our study also provides a reliable, systematic strategy to identify DNA methylation-regulated miRNAs by combining DNA methylation profiles and expression data

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Background Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Methods We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. Results A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35;

Newly described human polyomaviruses Merkel Cell, KI and WU are present in urban sewage and may represent potential environmental contaminants

Recently, three new polyomaviruses (KI, WU and Merkel cell polyomavirus) have been reported to infect humans. It has also been suggested that lymphotropic polyomavirus, a virus of simian origin, infects humans. KI and WU polyomaviruses have been detected mainly in specimens from the respiratory tract while Merkel cell polyomavirus has been described in a very high percentage of Merkel cell carcinomas. The distribution, excretion level and transmission routes of these viruses remain unknown