Prescription of memantine during non-stereotactic,brain-directed radiation among patients with brain metastases: a population-based study

Journal of Neuro-Oncology - Whole brain radiation therapy (WBRT) remains an important component of treatment for patients with multiple brain metastases (BrM) but is associated with significant...     

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma

Journal of Neuro-Oncology - We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). Primary outcomes were...     

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and non-hematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.     

Absolute and Relative Agreement between the Current and Modified Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) and the American Heart Association Healthy Diet Score (AHA-DS) in Post Myocardial Infarction Patients

The American Heart Association Diet Score (AHA-DS) defines the cardiovascular health, and the Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) was designed to evaluate diet quality in secondary cardiovascular prevention settings. Our aim was to assess the absolute and relative agreement between both tools in Brazilian adults after a myocardial infarction (MI). In this cross-sectional study, 473 individuals were included and had their diet assessed by a 24 h food recall and a semi-quantitative Food Frequency Questionnaire. The weighted Kappa between BALANCE DI and primary AHA-DS was 0.66 (95% CI: 0.08–0.21), and between BALANCE DI and total AHA-DS was 0.70 (95% CI: 0.20–0.32). To improve the agreement between the tools, modifications were made to the BALANCE DI scoring system. The weighted Kappa between New BALANCE DI and primary AHA-DS was 0.77 (95% CI: 0.36–0.48), and between BALANCE DI and total AHA-DS was 0.76 (95% CI: 0.34–0.46). The mean bias observed between the New BALANCE DI as compared to the primary and total AHA-DS was −16% (−51 to 19) and −8% (−41 to 24), respectively. Our results suggest that the New BALANCE DI may be a useful tool to evaluate diet quality in post MI patients.     

Extent and consequences of inadequate disease control among adults with a history of moderate to severe atopic dermatitis

Since control of atopic dermatitis (AD) remains challenging but has not been adequately characterized, the objective of this study was to characterize disease control among patients with a history of moderate to severe AD. Data were from the 2014 Adelphi US AD Disease Specific Programme, a cross‐sectional survey of physicians (n = 202) and their patients with history of moderate to severe AD (n = 1064, 54% female, 75% white, mean age 40 years). Inadequately controlled AD as rated by the physician was defined as currently flaring; deteriorating/changeable AD; or physician dissatisfaction with current control. The overall inadequate control rate was 58.7% (n = 625), which increased with current AD severity and was observed in 53.4% and 83.4% of patients receiving immunosuppressants and systemic corticosteroids, respectively. Relative to controls, inadequately controlled patients had poorer disease‐specific quality of life, higher level of work impairment, greater itch and sleep interference with daily living (all P < 0.05). Multivariate analysis showed factors significantly associated with inadequate control (all P < 0.05), including Hispanic race, symptoms on the head/neck or lower limbs, itch and sleep interference with daily living. A limitation of the study was reliance on accuracy of reporting, potential selection bias and cross‐sectional study design. In summary, there was a high rate and substantial impact of physician‐rated inadequately controlled disease among patients with a history of moderate to severe AD, suggesting the need for more effective therapies.     

Three‐dimensional cultures of mouse submandibular and parotid glands: a comparative study

Freshly isolated salivary cells can be plated on an extracellular matrix, such as growth factor‐reduced Matrigel (GFR‐MG), to induce the formation of three‐dimensional (3D) structures. Cells grown on GFR‐MG are able to form round structures with hollow lumina, capable of sustaining amylase expression. In contrast, cells grown on plastic do not exhibit these features. Our recent studies have used mouse parotid gland (PG) cells, grown on different extracellular matrices, as a model for acinar formation. However, PG cells were not able to respond to the secretory agonist carbachol beyond 5 days and did not sustain polarity over time, regardless of the substratum. An alternative option relies in the use of mouse submandibular glands (SMG), which are more anatomically accessible and yield a larger number of cells. We compared SMG and PG cell clusters (partially dissociated glands) for their ability to form hollow round structures, sustain amylase and maintain secretory function when grown on GFR‐MG. The results were as follows: (a) SMG cell clusters formed more organized and larger structures than PG cell clusters; (b) both SMG and PG cell clusters maintained α‐amylase expression over time; (c) SMG cell clusters maintained agonist‐induced secretory responses over time; and (d) SMG cell clusters maintained secretory granules and cell–cell junctions. These results indicate that mouse SMG cell clusters are more amenable for the development of a bioengineered salivary gland than PG cell clusters, as they form more organized and functional structures. Copyright © 2014 John Wiley & Sons, Ltd.