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

Distress after Preterm Birth A Discourse Analysis of Parents' Accounts and Photographs

Preterm birth is a distressing experience for parents. This distress may continue into early childhood, with negative consequences for parents' mental health and child development. The purpose of this study was to take an in-depth look at how parents formed their accounts of premature birth, postpartum distress, and lives as parents and partners. Discourse analysis of semi-structured interviews and photo-elicitation assignments were used to analyze the parents' experiences in the context of the couple relationship. The study population included 8 parents of premature infants born from 24 to 30 weeks gestation, who had experienced significant distress in and out of the hospital. Parents participated in the study when their children were between 15 months and 8 years old. In the initial interview parents described their experience of prematurity, emotional distress, and parenting. Participants returned for a second interview where they further described their distress using photographs they had newly taken or selected. Parents described the preterm birth, hospitalization, and aftermaths as ongoing traumatic events. Discourses of distress included the perfect child, the good mother, and the good father. Parents engaged these discourses in reconciling their loss of idealized birth and parenting and their roles after prematurity. Social isolation and disciplinary power were discourses that showed how parents struggled with interaction with their social networks and with health care providers and institutions. Photo-elicitation provided additional dimensions to the participants' accounts of distress. Findings highlighted how parents described their trauma and distress in ways not captured by psychiatric diagnoses such as depression and anxiety. Findings may help nurses be aware of the negative effects of preterm birth and respond to the parents' emotional needs

Advanced Practice Nursing Education: Challenges and Strategies

Nursing education programs may face significant difficulty as they struggle to prepare sufficient numbers of advanced practice registered nurses to fulfill the vision of helping to design an improved US healthcare system as described in the Institute of Medicine's “Future of nursing” report. This paper describes specific challenges and provides strategies to improve advanced practice nursing clinical education in order to ensure that a sufficient number of APRNs are available to work in educational, practice, and research settings. Best practices are identified through a review of classic and current nursing literature. Strategies include intensive interprofessional collaborations and radical curriculum revisions such as increased use of simulation and domestic and international service work. Nurse educators must work with all stakeholders to create effective and lasting change

Exploring Perinatal Nursing Care for Opioid Use Disorder: Knowledge, Stigma, and Compassion.

The opioid epidemic has greatly increased the number of pregnant women with opioid use and newborns exposed to opioids in utero. Mothers with opioid use disorder can face stigma by nurses in perinatal care settings, contributing to negative care experiences. A survey was distributed to nurses caring for mothers and newborns exposed to opioids in a large urban hospital in the Pacific Northwest United States (n = 89) from March to July 2019. Survey measures included participant characteristics, attitude toward substance use in pregnancy and postpartum (stigma, compassion satisfaction, comfort, and knowledge), and open-ended questions. Relationships among variables and questionnaire items were examined using Pearson\u27s correlations, 2-sample t tests, and simultaneous multiple linear regression. Qualitative description was used to analyze open-ended questions. Nurses\u27 stigma was negatively correlated with compassion satisfaction (r = -0.63), feeling knowledgeable (r = -0.36), and comfortable in providing care to this population (r = -0.44). Nurses identified defensiveness, lack of trust, and inadequate social support as key challenges in this patient population. Nurses suggested more support for mothers and nurses, increased nursing education, and clinical guidelines to improve clinical practice and foster therapeutic relationships. Findings highlight potential strategies to improve nursing care for chemically dependent mothers and their infants. These strategies may offer practical approaches to reduce stigma, develop therapeutic relationships, and improve patient outcomes

A Survey of Midwives\u27 Attitudes Toward Men in Midwifery.

INTRODUCTION: The midwifery profession in the United States demonstrates a significant lack of diversity. The critical need to address the lack of racial and ethnic diversity in the midwifery workforce is well recognized; little attention, however, has been given to gender diversity. This study focused on gender diversity within midwifery, specifically with regard to men who are midwives. Nearly 99% of midwives in the United States are women. No research has previously explored the attitudes of the predominantly female midwifery workforce toward its male members. METHODS: An invitation to an internet survey was sent to the American College of Nurse-Midwives (ACNM) membership. Quantitative and open-ended questions assessed attitudes toward and experiences with male midwives, whether members thought men belong in the profession, whether gender impacts quality of care, if ACNM should facilitate gender diversification, and whether exposure to male midwives impacts attitudes toward gender diversification. Data analysis of qualitative responses used a qualitative description methodology to identify common themes. RESULTS: Six thousand, nine hundred sixty-five surveys were distributed, and 864 participants completed the survey. Respondents reported beliefs that men belong in midwifery (71.4%), that gender does not affect quality of care (74%), and that ACNM should support gender diversity (72%). Respondents\u27 perspectives revealed 3 dichotomous themes pertaining to the core nature of midwifery and how men fit within the profession: 1) inclusion versus exclusion, 2) empowerment versus protection, and 3) sharing with versus taking from. Often, the same respondent expressed both aspects of the dichotomy simultaneously. DISCUSSION: This study contributes new information about midwives\u27 attitudes and beliefs toward gender diversity in midwifery in the United States. The values of professionalism, tradition, feminism, protection, and diversification inform participant responses. Findings support efforts toward gender diversification and have implications for implementation in education and practice

Synergy among Multiple Methodologies: Investigating Parents' Distress after Preterm Birth

Interpretive methodologies require a level of introspection and engagement that is different from that used in empirical and analytical methodologies. The use of multiple interpretive methodologies to explore a phenomenon, in the context of a single study, is a unique perspective for undertaking qualitative research. The purpose of this article is to illustrate the synergistic nature of combining interpretive methodologies to capture multiple facets of a phenomenon. We used two different philosophical orientations, Heideggerian hermeneutic phenomenology and Foucauldian discourse analysis not only to describe the differences in research questions, methods, and analyses, but also to illustrate the added insight gained from a multiple-methodological approach. The differences between interpretive methodologies, as well as the analytic value of this innovative approach, are nuanced and are best demonstrated through the analysis of an exemplar transcript using both methodologies. Although subtle methodological differences exist, the interpretations combined create a deepening understanding of the phenomenon. Awareness of how each interpretive tradition influences the language around the research question, the data collection and analysis, and overall integrity of the level of inquiry is crucial to maintaining a rigor in both traditions, yet recognition of multiple “truths” allows for a more holistic representation to be created

Pharmacokinetics of dacarbazine (DTIC) in pregnancy.

PURPOSE: The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites [5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC), 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-aminoimidazole-4-carboxamide (AIC)] during pregnancy (n = 2) and postpartum (n = 1). METHODS: Non-compartmental DTIC, MTIC, HMMTIC, and AIC pharmacokinetics (PK) were estimated in one case at 29 week gestation and 18 day postpartum and a second case at 32 week gestation, in women receiving DTIC in combination with doxorubicin, bleomycin, and vinblastine for treatment of Hodgkin\u27s lymphoma. Drug concentrations were measured by HPLC. RESULTS: In the subject who completed both pregnancy and postpartum study days, DTIC area under the concentration-time curve (AUC) was 27% higher and metabolite AUCs were lower by 27% for HMMTIC, 38% for MTIC, and 83% of AIC during pregnancy compared to postpartum. At 7 and 9 year follow-up, both subjects were in remission of their Hodgkin\u27s lymphoma. CONCLUSIONS: Based on these two case reports, pregnancy appears to decrease the metabolism of the pro-drug dacarbazine, likely through inhibition of CYP1A2 activity. Lower concentrations of active metabolites and decreased efficacy may result, although both these subjects experienced long-term remission of their Hodgkin\u27s lymphoma