A Pilot Study of the Preliminary Efficacy of Pain Buddy: A Novel Intervention for the Management of Children’s Cancer-Related Pain

Objectives Cancer‐related pain in children is prevalent and undermanaged. Mobile health (mHealth) applications provide a promising avenue to address the gap in pain management in children with cancer. Pain Buddy is a multicomponent mHealth application developed to manage cancer‐related pain in children. The goal of this paper is to present preliminary efficacy data of the impact of Pain Buddy on children\u27s pain severity and frequency. Methods In a randomized controlled trial over 60 days, children (N = 48) reported daily pain on a tablet while receiving usual care. Those in the intervention group (N = 20) received remote symptom monitoring and skills training for pain management. Children in the attention control group (N = 28) only reported on their pain. Results Both groups experienced significant reductions in average daily pain over the study period (B = −0.10, z = −3.40, P = 0.001), with no group differences evident (z = −0.83, P = 0.40). However, the intervention group reported significantly fewer instances of moderate to severe pain compared with the control group, t(4125) = 2.67, P = 0.007. In addition, the intervention group reported no instances of moderate to severe pain toward the end of the study period. Conclusion Pain Buddy is an innovative and interactive mHealth application that aims to improve pain and symptom management among children with cancer. The findings from this pilot study suggest that Pain Buddy may aid in the reduction of pain severity in children during cancer treatment

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

Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis

Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure

A pilot study of the preliminary efficacy of Pain Buddy: A novel intervention for the management of children's cancer‐related pain

Objectives Cancer‐related pain in children is prevalent and undermanaged. Mobile health (mHealth) applications provide a promising avenue to address the gap in pain management in children with cancer. Pain Buddy is a multicomponent mHealth application developed to manage cancer‐related pain in children. The goal of this paper is to present preliminary efficacy data of the impact of Pain Buddy on children\u27s pain severity and frequency. Methods In a randomized controlled trial over 60 days, children (N = 48) reported daily pain on a tablet while receiving usual care. Those in the intervention group (N = 20) received remote symptom monitoring and skills training for pain management. Children in the attention control group (N = 28) only reported on their pain. Results Both groups experienced significant reductions in average daily pain over the study period (B = −0.10, z = −3.40, P = 0.001), with no group differences evident (z = −0.83, P = 0.40). However, the intervention group reported significantly fewer instances of moderate to severe pain compared with the control group, t(4125) = 2.67, P = 0.007. In addition, the intervention group reported no instances of moderate to severe pain toward the end of the study period. Conclusion Pain Buddy is an innovative and interactive mHealth application that aims to improve pain and symptom management among children with cancer. The findings from this pilot study suggest that Pain Buddy may aid in the reduction of pain severity in children during cancer treatment