Background

Heart failure is a serious public health concern that afflicts millions of individuals in the United States. Development of behaviors that promote heart failure self-care may be imperative to reduce complications and avoid hospital re-admissions. Mobile health solutions, such as activity trackers and smartphone apps, could potentially help to promote self-care through remote tracking and issuing reminders.

Objective

The objective of this study was to ascertain heart failure patients' interest in a smartphone app to assist them in managing their treatment and symptoms and to determine factors that influence their interest in such an app.

Methods

In the clinic waiting room on the day of their outpatient clinic appointments, 50 heart failure patients participated in a self-administered survey. The survey comprised 139 questions from previously published, institutional review board-approved questionnaires. The survey measured patients' interest in and experience using technology as well as their function, heart failure symptoms, and heart failure self-care behaviors. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was among the 11 questionnaires and was used to measure the heart failure patients' health-related quality of life through patient-reported outcomes.

Results

Participants were aged 64.5 years on average, 32% (16/50) of the participants were women, and 91% (41/45) of the participants were determined to be New York Heart Association Class II or higher. More than 60% (30/50) of the survey participants expressed interest in several potential features of a smartphone app designed for heart failure patients. Participant age correlated negatively with interest in tracking, tips, and reminders in multivariate regression analysis (P<.05). In contrast, MLHFQ scores (worse health status) produced positive correlations with these interests (P<.05).

Conclusions

The majority of heart failure patients showed interest in activity tracking, heart failure symptom management tips, and reminder features of a smartphone app. Desirable features and an understanding of factors that influence patient interest in a smartphone app for heart failure self-care may allow researchers to address common concerns and to develop apps that demonstrate the potential benefits of mobile technology.

Background

Around 50% of hospital readmissions due to heart failure are preventable, with lack of adherence to prescribed self-care as a driving factor. Remote tracking and reminders issued by mobile health devices could help to promote self-care, which could potentially reduce these readmissions.

Objective

We sought to investigate two factors: (1) feasibility of enrolling heart failure patients in a remote monitoring regimen that uses wireless sensors and patient-reported outcome measures; and (2) their adherence to using the study devices and completing patient-reported outcome measures.

Methods

Twenty heart failure patients participated in piloting a remote monitoring regimen. Data collection included: (1) physical activity using wrist-worn activity trackers; (2) body weight using bathroom scales; (3) medication adherence using smart pill bottles; and (4) patient -reported outcomes using patient-reported outcome measures.

Results

We evaluated 150 hospitalized heart failure patients and enrolled 20 individuals. Two factors contributed to 50% (65/130) being excluded from the study: smartphone ownership and patient discharge. Over the course of the study, 60.0% of the subjects wore the activity tracker for at least 70% of the hours, and 45.0% used the scale for more than 70% of the days. The pill bottle was used less than 10% of the days by 55.0% of the subjects.

Conclusions

Our method of recruiting heart failure patients prior to hospital discharge may not be feasible as the enrollment rate was low. Once enrolled, the majority of subjects maintained a high adherence to wearing the activity tracker but low adherence to using the pill bottle and completing the follow-up surveys. Scale usage was fair, but it received positive reviews from most subjects. Given the observed usage and feedback, we suggest mobile health-driven interventions consider including an activity tracker and bathroom scale. We also recommend administering a shorter survey more regularly and through an easier interface.

Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy^1-3. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB⁴, mutations that cause loss of MHC-I are rarely found⁵ despite the frequent downregulation of MHC-I expression^6-8. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8⁺ T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.

Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy^1-3. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB⁴, mutations that cause loss of MHC-I are rarely found⁵ despite the frequent downregulation of MHC-I expression^6-8. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8⁺ T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.