Summer of My American Soldier: Perimeter Veterans Multi-Service Center

https://digitalcommons.pcom.edu/bridging_gaps2015/1007/thumbnail.jp

Use of Nanofibers to Strengthen Hydrogels of Silica, Other Oxides, and Aerogels

Research has shown that including up to 5 percent w/w carbon nanofibers in a silica backbone of polymer crosslinked aerogels improves its strength, tripling compressive modulus and increasing tensile stress-at-break five-fold with no increase in density or decrease in porosity. In addition, the initial silica hydrogels, which are produced as a first step in manufacturing the aerogels, can be quite fragile and difficult to handle before cross-linking. The addition of the carbon nanofiber also improves the strength of the initial hydrogels before cross-linking, improving the manufacturing process. This can also be extended to other oxide aerogels, such as alumina or aluminosilicates, and other nanofiber types, such as silicon carbide

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A roadmap to reduce information inequities in disability with digital health and natural language processing

People with disabilities disproportionately experience negative health outcomes. Purposeful analysis of information on all aspects of the experience of disability across individuals and populations can guide interventions to reduce health inequities in care and outcomes. Such an analysis requires more holistic information on individual function, precursors and predictors, and environmental and personal factors than is systematically collected in current practice. We identify three key information barriers to more equitable information: (1) a lack of information on contextual factors that affect a person’s experience of function; (2) under-emphasis of the patient’s voice, perspective, and goals in the electronic health record; and (3) a lack of standardized locations in the electronic health record to record observations of function and context. Through analysis of rehabilitation data, we have identified ways to mitigate these barriers through the development of digital health technologies to better capture and analyze information about the experience of function. We propose three directions for future research on using digital health technologies, particularly natural language processing (NLP), to facilitate capturing a more holistic picture of a patient’s unique experience: (1) analyzing existing information on function in free text documentation, (2) developing new NLP-driven methods to collect information on contextual factors, and (3) collecting and analyzing patient-reported descriptions of personal perceptions and goals. Multidisciplinary collaboration between rehabilitation experts and data scientists to advance these research directions will yield practical technologies to help reduce inequities and improve care for all populations

A roadmap to reduce information inequities in disability with digital health and natural language processing.

People with disabilities disproportionately experience negative health outcomes. Purposeful analysis of information on all aspects of the experience of disability across individuals and populations can guide interventions to reduce health inequities in care and outcomes. Such an analysis requires more holistic information on individual function, precursors and predictors, and environmental and personal factors than is systematically collected in current practice. We identify 3 key information barriers to more equitable information: (1) a lack of information on contextual factors that affect a person's experience of function; (2) underemphasis of the patient's voice, perspective, and goals in the electronic health record; and (3) a lack of standardized locations in the electronic health record to record observations of function and context. Through analysis of rehabilitation data, we have identified ways to mitigate these barriers through the development of digital health technologies to better capture and analyze information about the experience of function. We propose 3 directions for future research on using digital health technologies, particularly natural language processing (NLP), to facilitate capturing a more holistic picture of a patient's unique experience: (1) analyzing existing information on function in free text documentation; (2) developing new NLP-driven methods to collect information on contextual factors; and (3) collecting and analyzing patient-reported descriptions of personal perceptions and goals. Multidisciplinary collaboration between rehabilitation experts and data scientists to advance these research directions will yield practical technologies to help reduce inequities and improve care for all populations

Micronutrient supplementation has limited effects on intestinal infectious disease and mortality in a Zambian population of mixed HIV status: a cluster randomized trial.

BACKGROUND: Diarrheal disease remains a major contributor to morbidity and mortality in Africa, but host defense against intestinal infection is poorly understood and may depend on nutritional status. OBJECTIVE: To test the hypothesis that defense against intestinal infection depends on micronutrient status, we undertook a randomized controlled trial of multiple micronutrient supplementation in a population where there is borderline micronutrient deficiency. DESIGN: All consenting adults (> or =18 y) living in a carefully defined sector of Misisi, Lusaka, Zambia, were included in a cluster-randomized (by household), double-blind, placebo-controlled trial with a midpoint crossover. There were no exclusion criteria. Participants were given a daily tablet containing 15 micronutrients at just above the recommended nutrient intake or placebo. The primary endpoint was the incidence of diarrhea; secondary endpoints were severe episodes of diarrhea, respiratory infection, nutritional status, CD4 count, and mortality. RESULTS: Five hundred participants were recruited and followed up for 3.3 y (10,846 person-months). The primary endpoint, incidence of diarrhea (1.4 episodes/y per person), did not differ with treatment allocation. However, severe episodes of diarrhea were reduced in the supplementation group (odds ratio: 0.50; 95% CI: 0.26, 0.92; P = 0.017). Mortality was reduced in HIV-positive participants from 12 with placebo to 4 with supplementation (P = 0.029 by log-rank test), but this was not due to changes in CD4 count or nutritional status. CONCLUSION: Micronutrient supplementation with this formulation resulted in only modest reductions in severe diarrhea and reduced mortality in HIV-positive participants. The trial was registered as ISRCTN31173864