Outcomes of multimodal therapy in a large series of patients with anaplastic thyroid cancer

Background The role of radiotherapy (RT) in the treatment of patients with anaplastic thyroid cancer (ATC) for local tumor control is critical because mortality often is secondary to complications of tumor volume rather than metastatic disease. Herein, the authors report the long-term outcomes of RT for patients with ATC. Methods A total of 104 patients with histologically confirmed ATC were identified who presented to the study institution between 1984 and 2017 and who received curative-intent or postoperative RT. Locoregional progression-free survival (LPFS), overall survival (OS), and distant metastasis-free survival were assessed. Results The median age of the patients was 63.5 years. The median follow-up was 5.9 months (interquartile range, 2.7-17.0 months) for the entire cohort and 10.6 months (interquartile range, 5.3-40.0 months) for surviving patients. Thirty-one patients (29.8%) had metastatic disease prior to the initiation of RT. Concurrent chemoradiation was administered in 99 patients (95.2%) and 53 patients (51.0%) received trimodal therapy. Systemic therapy included doxorubicin (73.7%), paclitaxel with or without pazopanib (24.3%), and other systemic agents (2.0%). The 1-year OS and LPFS rates were 34.4% and 74.4%, respectively. On multivariate analysis, RT >= 60 Gy was associated with improved LPFS (hazard ratio [HR], 0.135; P = .001) and improved OS (HR, 0.487; P = .004), and trimodal therapy was associated with improved LPFS (HR, 0.060; P = .017). The most commonly observed acute grade 3 adverse events included dermatitis (20%) and mucositis (13%), with no grade 4 subacute or late adverse events noted (adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Conclusions RT appears to demonstrate a dose-dependent, persistent LPFS and OS benefit in patients with locally advanced ATC with an acceptable toxicity profile. Aggressive RT should be strongly considered for the treatment of patients with ATC as part of a trimodal treatment approach

Developing Population Health Surveillance Using mHealth in Low-Resource Settings: Qualitative Assessment and Pilot Evaluation

BackgroundPopulation surveillance data are essential for understanding population needs and evaluating health programs. Governmental and nongovernmental organizations in western Myanmar did not previous have means for conducting robust, electronic population health surveillance. ObjectiveThis study involved developing mobile health (mHealth)–based population health surveillance in a rural, low-resource setting with minimal cellular infrastructure in western Myanmar. This was an early formative study in which our goal was to establish the initial feasibility of conducting mHealth population health surveillance, optimizing procedures, and building capacity for future work. MethodsWe used an iterative design process to develop mHealth-based population health surveillance focused on general demographics (eg, total census, age category, sex, births, and deaths). Interviews were conducted with international consultants (nurse midwives) and local clinicians (nurses and physicians) in Myanmar. Our analytic approach was informed by the Systems Engineering Initiative for Patient Safety work systems model to capture the multilevel user needs for developing health interventions, which was used to create a prototype data collection tool. The prototype was then pilot-tested in 33 villages to establish an initial proof of concept. ResultsWe conducted 7 interviews with 5 participants who provided feedback regarding the domains of the work system, including environmental, organizational, sociocultural, technological, informational, and task- and people-based considerations, for adapting an mHealth tool. Environmental considerations included managing limited electricity and internet service. Organizational needs involved developing agreements to work within existing government infrastructure as well as leveraging the communal nature of societies to describe the importance of surveillance data collection and gain buy-in. Linguistic diversity and lack of experience with technology were both cited as people- and technology-based aspects to inform prototype design. The use of mobile tools was also viewed as a means to improve the quality of the data collected and as a feasible option for working in settings with limited internet access. Following the prototype design based on the findings of initial interviews, the mHealth tool was piloted in 33 villages, allowing our team to collect census data from 11,945 people for an initial proof of concept. We also detected areas of potentially missing data, which will need to be further investigated and mitigated in future studies. ConclusionsPrevious studies have not focused heavily on the early stages of developing population health surveillance capacity in low- and middle-income countries. Findings related to key design considerations using a work systems lens may be informative to others developing technology-based solutions in extremely low-resource settings. Future work will involve collecting additional health-related data and further evaluating the quality of the data collected. Our team established an initial proof of concept for using an mHealth tool to collect census-related information in a low-resource, extremely rural, and low-literacy environment

Differential requirements for the Ets transcription factor Elf-1 in the development of NKT cells and NK cells

E26 Transformation specific (Ets) family transcription factors control the expression of a large number of genes regulating hematopoietic cell development and function. Two such transcription factors, Ets-1 and myeloid Elf-1–like factor (MEF), have been shown to play critical roles in both natural killer (NK)– and NKT-cell development, but not in the development of conventional T cells. In this study, we address the role of E74-like factor 1 (Elf-1), another Ets family transcription factor that is closely related to MEF but divergent from Ets-1, in NK- and NKT-cell development using Elf-1–deficient (Elf-1−/−) mice. Whereas the proportion of NK cells in Elf-1−/− mice was normal, the proportion of NKT cells was significantly reduced in the thymus and periphery of Elf-1−/− mice compared with wild-type (WT) mice. Although Ets-1–deficient mice lack NKT cells altogether, Elf-1−/− mice exhibited only a partial block in NKT-cell development caused by a cell-intrinsic defect in the selection, survival, and maturation of NKT cells. In addition, residual NKT cells found in Elf-1−/− mice produced less cytokine upon antigen stimulation compared with WT NKT cells. Our data demonstrate that Elf-1 plays an important and nonredundant role in the development and function of NKT cells, but is not involved in NK-cell development