Citations

Abstract TNF-related apoptosis-inducing ligand (TRAIL) was initially described to induce apoptosis of tumor cells and/or virally infected cells, although sparing normal cells, and has been implicated in the pathogenesis of HIV disease. We previously identified TRAILshort, a TRAIL splice variant, in HIV-infected patients and characterized it as being a dominant negative ligand to subvert TRAIL-mediated killing. Herein, using single-cell genomics we demonstrate that TRAILshort is produced by HIV-infected cells, as well as by uninfected bystander cells, and that the dominant stimulus which induces TRAILshort production are type I IFNs and TLR7, TLR8, and TLR9 agonists. TRAILshort has a short t1/2 by virtue of containing a PEST domain, which targets the protein toward the ubiquitin proteasome pathway for degradation. Further we show that TRAILshort binds preferentially to TRAIL receptors 1 and 2 with significantly reduced interaction with the decoy TRAIL receptors 3 and 4. Recombinant TRAILshort is sufficient to protect cells against TRAIL-induced killing, whereas immunodepletion of TRAILshort with a specific Ab restores TRAIL sensitivity. Importantly we show that TRAILshort is shed in microvesicles into the cellular microenvironment and therefore confers TRAIL resistance not only on the cell which produces it, but also upon neighboring bystander cells. These results establish a novel paradigm for understanding and overcoming TRAIL resistance, in particular how HIV-infected cells escape immune elimination by the TRAIL:TRAILshort receptor axis.

Purpose: To evaluate a healthy eating and physical activity intervention for immigrant families, derived through community-based participatory research. Design: The Healthy Immigrant Families study was a randomized controlled trial with delayed intervention control group, with families as the randomization unit. Setting: US Midwest city. Participants: Participants were recruited by community partners from Hispanic, Somali, and Sudanese immigrant communities. Intervention: Family health promoters from participating communities delivered 6 healthy eating modules, 4 physical activity modules, and 2 modules synthesizing information in 12 home visits (60-90 minutes) within the first 6 months. Up to 12 follow-up phone calls to each participant occurred within the second 6 months. Measures: Primary measures were dietary quality measured with weekday 24-hour recall and reported as Healthy Eating Index score (0-100) and physical activity measured with accelerometers (14 wear days) at baseline, 6, 12, and 24 months. Results: In total, 151 persons (81 adolescents and 70 adults; 44 families) were randomly assigned. At 12 months, significant improvement occurred in Healthy Eating Index scores for adults in the intervention group compared with controls (change, +8.6 vs −4.4; P < .01) and persisted at 24 months (+7.4 from baseline; P < .01). No differences were observed for adolescents and no significant differences occurred between groups for physical activity. Conclusion: This intervention produced sustained dietary quality improvement among adults but not among adolescents. Program outcomes are relevant to communities working to decrease cardiovascular risk among immigrant populations.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.

32 Background: The link between patient concerns and clinical systems delivery is often suboptimal. We developed a case management system for palliative care which transforms the patient’s greatest concerns into actionable clinical pathways. Methods: The system collects patients’ single greatest and second greatest concern plus Quality of Life (QOL) data (pain, fatigue and overall QOL single-items scored 0-10 with 10 representing worst pain/fatigue, or best QOL) and produces a report to guide the physician and patient. The system presents ten “buttons” in a xylophone-like grid: Personal Relationships, Monitoring Health, Emotional Health, Money, Health Behaviors, Medication Troubles, Care Access, Work Worries, Physical Health and Care Planning. We performed a quality improvement study at Mayo Clinic sites. Results: 409 patients participated in at least one survey from 11/04/2015 to 9/22/2016 (620 total surveys). The most common Main Concern was Physical Health 265/620 (43%) followed by Monitoring Health (17%), Medication (8%), and Emotional Health, Money, and Health Behaviors (7% each), Personal Relationships (6%). Future Care Planning, Work, and Care Access/Coordination were rarely chosen ( < 5%). The most common Second greatest concern was Health Behaviors 73/409 (18%) followed by Physical Health (17%). 93/122 (67%) patients changed their greatest concern from baseline to subsequent visits. The mean QOL, fatigue and pain at baseline were 4.8, 6.0 and 4.8 respectively, indicating substantial clinically significant deficits. Post baseline mean scores improved by a maximum of 0.8, 1.1, and 0.9 points respectively, representing clinically meaningful effects. On average it took 8 minutes for patients to use the system. Conclusions: The system was quick and easy to utilize. The personal impact concerns (physical/emotional health, medications) were most often cited as the greatest concern, while care issues were de-emphasized by patients. Patients and physicians praised the system for making visits more efficient and raising issues that otherwise might not have been addressed. This system has the potential to improve patient well-being and clinical outcomes, as well as to reduce burden on clinicians and optimize case management activities.

177 Background: Dignity Therapy (DT) is a psychosocial intervention used primarily at the end of life to improve quality of life and promote patient dignity, but many individuals are unable to complete it due to health decline/death. In addition, when individuals face potential mortality, they evaluate life plans to determine tasks and behaviors most important to them. Consistent with guidelines to provide palliative care interventions simultaneously with cancer treatment, the purpose of this study was to evaluate initial patient-reported outcomes of an intervention combination (Dignity Therapy + Life Plan [DT/LP]) for those with advanced pancreatic or lung cancer receiving treatment within a year of diagnosis. Methods: This was a single-arm, Phase I/II pilot study, conducted in the outpatient setting at an NCI-designated comprehensive cancer center. Dignity Therapy consisted of a focused life review intervention delivered during three outpatient oncology encounters for each patient. Interviews were audiotaped, transcribed, and edited to produce a legacy document. Participants scribed a list of 3-6 life goals for the LP intervention. Outcomes measured at baseline, immediately post DT/LP, and 3 months later were distress (Distress Thermometer), quality of life (FACT and LASA), spirituality (FaCIT-Sp-12), dignity (Patient Dignity Inventory), and purpose in life (Purpose in Life Test- Short Form). Data were analyzed with one-sample, two-sided t-tests (alternate: Wilcoxan). Results: Eighteen advanced pancreatic or lung cancer patients enrolled, mean age 64. There were no significant differences among all variables from baseline to post-DT/LP and 3 months later, with the exception of less distress experienced between baseline and 3 months after DT/LP ( p= 0.04). Conclusions: The DT/LP intervention did not show improvements in these psychosocial outcomes, but patients with advanced cancer typically experience worsening physical and psychosocial symptoms with active treatment. Therefore, maintaining these outcomes from baseline is a worthy goal, as we may be preventing further morbidity in an advanced cancer population. Further research is needed, however, given this small sample size. Clinical trial information: NCT02132325.