Anatomic predictors of recurrence after cryoablation for atrial fibrillation: a computed tomography based composite score

Journal of Interventional Cardiac Electrophysiology - Effective pulmonary vein isolation (PVI) with cryoablation depends on adequate occlusion of pulmonary veins (PV) by the cryoballoon and is...     

CALLA-positive myeloma: an aggressive subtype with poor survival

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.     

High-dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphoma

The transformation of follicular lymphoma (FL) to high-grade histology occurs in up to 70% of patients. The role of hematopoietic stem cell transplantation (HSCT) in transformed FL is poorly defined. Twenty-four FL patients with histologically confirmed transformation to diffuse large B-cell lymphoma underwent unpurged autologous HSCT at our institution. Their median age was 56 yr. The median number of prior chemotherapies was 2 (range 1-6). Thirteen patients had residual nodal disease measuring more than 2 cm and four patients had bulky disease at the time of HSCT. Six patients had refractory disease at transplantation. At a median follow-up of 38 months, 3-yr progression-free survival following autologous HSCT was 40%. The 3-yr overall survival was 52%. The cumulative incidence of relapse and non-relapse mortality rate was 41% and 25%, respectively.     

Survey of County-Level Heat Preparedness and Response to the 2011 Summer Heat in 30 U.S. States

Background: Adapting to extreme heat is becoming more critical as our climate changes. Previous research reveals that very few communities in the United States have programs to sufficiently prevent health problems during hot weather.Objective: Our goal was to examine county-level local heat preparedness and response in 30 U.S. states following the unusually hot summer of 2011.Methods: Using a multimodal survey approach, we invited local health and emergency response departments from 586 counties to participate in the largest survey to date of heat preparedness and response in the United States. County-level responses were pooled into national and regional-level summaries. Logistic regressions modeled associations between heat planning/response and county characteristics, including population, poverty rates, typical summer weather, and 2011 summer weather.Results: Of 586 counties, 190 (32%) responded to the survey. Only 40% of these counties had existing heat plans. The most common heat responses were communication about heat, outreach, and collaborations with other organizations. Both heat preparedness and heat response were, on average, more extensive in counties with higher populations, lower poverty rates, and lower percentages of older people. Heat response was generally more extensive in counties with heat plans.Conclusions: Most responding counties were underprepared for extreme heat in 2011 and lacked a formal response plan. Because counties with heat plans were more likely to act to prevent adverse heat impacts to residents, local health departments should consider adopting such plans, especially because increased extreme heat is anticipated with further climate change.Citation: White-Newsome JL, Ekwurzel B, Baer-Schultz M, Ebi KL, O’Neill MS, Anderson GB. 2014. Survey of county-level heat preparedness and response to the 2011 summer heat in 30 U.S. States. Environ Health Perspect 122:573–579; http://dx.doi.org/10.1289/ehp.1306693     

Estimating the Health Effects of Greenhouse Gas Mitigation Strategies: Addressing Parametric,Model, and Valuation Challenges

Background: Policy decisions regarding climate change mitigation are increasingly incorporating the beneficial and adverse health impacts of greenhouse gas emission reduction strategies. Studies of such co-benefits and co-harms involve modeling approaches requiring a range of analytic decisions that affect the model output.Objective: Our objective was to assess analytic decisions regarding model framework, structure, choice of parameters, and handling of uncertainty when modeling health co-benefits, and to make recommendations for improvements that could increase policy uptake.Methods: We describe the assumptions and analytic decisions underlying models of mitigation co-benefits, examining their effects on modeling outputs, and consider tools for quantifying uncertainty.Discussion: There is considerable variation in approaches to valuation metrics, discounting methods, uncertainty characterization and propagation, and assessment of low-probability/high-impact events. There is also variable inclusion of adverse impacts of mitigation policies, and limited extension of modeling domains to include implementation considerations. Going forward, co-benefits modeling efforts should be carried out in collaboration with policy makers; these efforts should include the full range of positive and negative impacts and critical uncertainties, as well as a range of discount rates, and should explicitly characterize uncertainty. We make recommendations to improve the rigor and consistency of modeling of health co-benefits.Conclusion: Modeling health co-benefits requires systematic consideration of the suitability of model assumptions, of what should be included and excluded from the model framework, and how uncertainty should be treated. Increased attention to these and other analytic decisions has the potential to increase the policy relevance and application of co-benefits modeling studies, potentially helping policy makers to maximize mitigation potential while simultaneously improving health.Citation: Remais JV, Hess JJ, Ebi KL, Markandya A, Balbus JM, Wilkinson P, Haines A, Chalabi Z. 2014. Estimating the health effects of greenhouse gas mitigation strategies: addressing parametric, model, and valuation challenges. Environ Health Perspect 122:447–455; http://dx.doi.org/10.1289/ehp.1306744     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.     

Expression of mTOR signaling pathway markers in prostate cancer progression

BACKGROUND: The PI3K/AKT/mTOR pathway is central to prostate cancer progression. A preliminary investigation of immuno-histochemical expression of mammalian target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of expression in prostate tissue. METHODS: Immunohistochemistry was performed on a custom-made prostate tissue array. Mean long scores and variability of long scores for each marker were recorded for normal lumenal cells, prostate intraepithelial neoplasia (PIN), and cancer. RESULTS: Expression of PTEN decreased and mTOR signaling pathway markers increased in PIN and in cancer as compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression of 4E-BP1 was significantly higher than with any other marker. DISCUSSION: Results suggest that 4E-BP1 overexpression is strongly associated with prostate cancer, especially when combined with PTEN and mTOR expression data. Hierarchical clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer cell populations in most cases.