Publications

OBJECTIVES: Mobile health (mHealth) technology has been utilized to offer self-management tools to people with pain, including symptom tracking. Existing mobile tracking applications (apps) for chronic pain management have demonstrated reliability, feasibility, improved coping, and reduced health care utilization. Unfortunately, adherence in using a pain app can be problematic with many not using or discontinuing its use early. The current study aimed to investigate the impact that pain self-efficacy, pain conceptualizations, and patient perception of pain care providers, have on engagement with a mobile pain tracking app.

METHODS: Seventy-six (N=76) individuals with chronic pain downloaded a pain app and completed questionnaires assessing their pain and use of a pain app 3 months after they had downloaded the app. Associations with engagement with the app, defined as the number of daily diaries completed, and demographic and self-report questionnaire data were examined.

RESULTS: Results showed that engagement with the app was unrelated to self-efficacy and pain conceptualization but significantly related to positive perceptions of their pain care providers. Patients with more severe pain were found to have lower self-efficacy, less understanding of the biopsychosocial model of pain, and lower satisfaction with their involvement in their pain care decisions. Surprisingly, those who engaged more with the app demonstrated lower self-efficacy as compared with those who used the pain app less.

DISCUSSION: These findings highlight the importance of the patient-provider relationship in engaging with mHealth technology for pain management. Results further imply that longer-term use of mHealth tools may not be perceived as adaptive or clinically helpful for certain individuals.

AIMS: In the follow-up of patients with mitral regurgitation (MR), assessment of left ventricular (LV) dilatation using standard echocardiography often yields inconsistent results. We investigated whether measuring 3D LV end-systolic volume (3DLVESV) improves risk stratification in moderate or greater MR.

METHODS AND RESULTS: In the prospective 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation (3D-PRIME) study, 227 patients -142 with primary (PMR) and 85 secondary MR (SMR)- underwent 2D/3D echocardiography. 3DLVESV was increased if ≥41.5/35 mL/m², and LV end-systolic diameter (LVESD) enlarged if ≥39.8/34.8 mm in men/women. The primary outcome was a composite of MR progression towards intervention, death, or heart failure hospitalization (HFH). Death or HFH was a secondary outcome.At baseline, 28% of PMR and 54% of SMR patients had increased 3DLVESV. After 21 (15-25) months, increased 3DLVESV was associated with 1.9-fold (1.2-3.2) higher adjusted risk of the primary outcome in PMR, and 4.1-fold (1.6-10.7) higher risk of death or HFH in SMR (P < 0.05). 3DLVESV and LVESD concordantly identified LV dilatation in 20% of PMR patients and were discordant in 27%. Both patients with increased 3DLVESV only, and those with increased both 3DLVESV and LVESD, had high risk of the primary outcome after adjusting for recommendations for intervention in PMR: HR 7.1 (2.9-16.9) and 4.9 (2.1-11.1), respectively (P < 0.001).

CONCLUSION: Increased 3DLVESV is associated with a higher risk of adverse events in patients with significant MR. In PMR, evaluating LV dilatation using both 3DLVESV and LVESD may enhance risk stratification and aid in patient selection for close follow-up.

CLINICALTRIALSGOV IDENTIFIER: NCT04442828, 17 April 2020.

INTRODUCTION: Intimate partner violence (IPV) has been associated with various adverse health outcomes, and these outcomes may be worse in those experiencing IPV-related head injuries. Cognitive, motor, and psychiatric symptoms associated with these exposures are incompletely understood.

METHODS: In this cross-sectional survey study, participants completed questionnaires assessing demographics, IPV-related exposure, depression, anxiety, cognitive, and neurobehavioral symptoms. Participants were stratified into groups 1) without IPV history ('controls,' n = 1032), 2) with IPV history without IPV-related head injury ('IPV-only,' n = 163), and 3) with IPV-related head injury ('IPV-HI,' n = 102). ANCOVAs and logistic regressions controlling for age, sex, and race were used for comparison with subsequent pairwise comparisons using Tukey's post-hoc and estimated marginal means.

RESULTS: IPV groups had greater rates of all psychiatric conditions reported, general health problems including sleep difficulties and chronic pain, and motor symptoms (all p < 0.05). Compared to IPV-only, the IPV-HI group reported greater rates of migraines, chronic pain, and suicidal ideation, as well as greater anxiety, cognitive difficulties, and neurobehavioral symptoms (all p < 0.05).

CONCLUSION: IPV groups reported more health issues than controls, and those with IPV-HI had the greatest rates of general health, cognitive, psychiatric, and neurobehavioral difficulties. These findings provide novel insight into IPV and IPV-related head injury outcomes.

Nature employs post-translational modifications (PTMs) to induce proximity between proteins by engendering new interactions. Furthermore, we find that protein ligands are invariably proximal to a lysine. Inspired by these two observations, we developed group-transfer chimeras (GRCs) that append a moiety-of-interest to the lysine side chain. GRCs employ a protein's ligand and a handle with a transferase-type reactivity to modify the proximal lysine. Contemporary lysine-targeting group-transfer handles were incompatible with GRCs due to their hydrolytic instability, large size, high reactivity, and synthetic incompatibility with diverse ligands. Accordingly, we developed an N-(sulfonyl)-N-(trifluoroethyl)-ethanamide (SuFA) handle that is stable, small, and exhibits tunable reactivity and synthetic compatibility with diverse ligands and proteins. Using GRCs that group-transfer binders of tags (e.g., HaloTag, FKBP) onto proteins overexpressed in cancer cells, we displayed these binders on the surface of the cancer cell. With a universal T cell engager (UniTE) that binds to the displayed ligands and T cells, these GRCs induced proximity between cancer cells and cytotoxic T cells, leading to the latter's activation. We envision the GRC platform to find utility in basic research and biomedicine.

BACKGROUND & AIMS: Endothelial cells (ECs) display myriad protective roles that support tissue homeostasis. Embedding healthy ECs in 3D scaffolds stabilizes their phenotype to maximize reparative effects and shields immunogenicity. Here, we evaluate the protective effects of matrix-embedded ECs (MEECs) in liver explants and models of chronic liver disease.

METHODS: Precision cut liver slices (PCLS) from patients with cirrhosis (n = 8) and fibrotic or healthy mice (n = 6) were co-cultured with MEECs for 24 h and hepatic viability and inflammation were analyzed. The protective effects of the MEECs secretome were explored in vitro. MEECs were perihepatically or subcutaneously implanted for 1 week in fibrotic mice with or without hepatectomy (n = 6) to evaluate their effects on liver inflammation, regeneration, and fibrosis.

RESULTS: MEECs protected liver viability in PCLS from patients with cirrhosis (ATP/protein, 2.7 vs. 5.0, p = 0.01) and fibrotic (5.3 vs. 7.1, p = 0.01) or healthy (7.8 vs. 10.6, p = 0.01) mice, and reduced injury-induced inflammation. MEECs produced hepatocyte growth factor and fibroblast growth factor 2, which were associated with improved hepatic viability and anti-inflammatory macrophage polarization, respectively. Perihepatic implantation of MEECs in fibrotic mice with or without hepatectomy reduced inflammation and hepatic damage and exhibited pro-regenerative and antifibrotic properties (Sirius red+ area, 8.3 vs. 6.4, p = 0.005). These antifibrotic effects were associated with higher production of heparan sulfate and metalloproteinases 2 and 9, and mitigation of hepatic stellate cell activation. Implantation of MEECs at a distance from the liver did not reduce liver injury, inflammation, or fibrosis.

CONCLUSIONS: Endothelial-hepatocyte regulation is essential in liver repair, and matrix-embedded endothelial cells (MEECs) appear to be a potential therapy for chronic liver injury and ex situ preservation of liver grafts.

IMPACT AND IMPLICATIONS: Organ transplantation is the most effective therapy for advanced liver disease, yet remains limited by preservation of harvested graft viability and injury-induced inflammation post implantation. Healthy ECs display myriad protective roles that contribute to tissue homeostasis. In this study, we show how MEECs preserve cell viability and reduce inflammation in hepatic explants and display anti-inflammatory, antifibrotic and pro-regenerative properties in the liver of fibrotic mice. These dynamic and unique hepatoprotective properties of MEECs highlight their potential therapeutic utility for chronic liver injury or ex situ conservation of liver grafts.

OBJECTIVES: Randomized controlled trials (RCTs) of the Collaborative Care Model demonstrate strong evidence for effectively managing depression in a stepped-care approach across diverse patient populations. Despite alignment with the American Society of Clinical Oncology guidelines, which recommend a stepped-care approach for managing depression and anxiety in cancer patients, implementation of collaborative care in cancer centers remains limited and sparse real-world data exist. The Supportive Oncology Collaborative, a program integrating behavioral health and palliative care, was developed at an NCI-designated academic cancer center. This study aims to evaluate depression outcomes within this collaborative care program.

METHODS: A retrospective analysis was conducted on patients with at least 2 Patient Health Questionnaire-9 (PHQ-9) scores recorded within a 12-month period between January 2022 and December 2023 at 1 regional campus. Depression response, defined as a 50% reduction in PHQ-9 scores, was assessed at 12 and 24 weeks. Response rates were compared to those reported in RCTs of collaborative care.

RESULTS: Mean PHQ-9 scores were 17.3 at baseline (n = 47), 11.1 at 12 weeks (n = 43), and 10.1 at 24 weeks (n = 22). Depression response rates were 34.9% at 12 weeks (n = 43) and 54.5% at 24 weeks (n = 22).

SIGNIFICANCE OF RESULTS: We observed depression response rates comparable to those reported in RCTs of collaborative care in individuals with cancer. However, the high proportion of missing data highlights the difficulty of tracking outcomes in real-world clinical settings and the need for further evaluation and strategies to improve data completeness.

Major depressive disorder (MDD) involves both central nervous system dysfunction and systemic immune alterations. Using a systems biology approach, we investigated whether peripheral leukocytes exhibit transcriptional changes in genes annotated to synaptic processes, molecular functions typically associated with neurons but also possibly implicated in immune cell biology. A meta-analysis of transcriptomic data from 3072 individuals identified 1383 meta-differentially expressed genes (metaDEGs) in leukocytes, including 73 whose known functions are linked to synaptic biology. Among them, functional enrichment analysis indicated synapse-related metaDEGs (48 downregulated, 25 upregulated) involved in synaptic vesicle cycling, neurotransmitter signaling, synaptic assembly, and neurogenesis. Linear discriminant analysis (LDA) identified 18 of these genes that robustly distinguished MDD patients from healthy controls across independent datasets. Notably, we identified metaDEGs shared between leukocytes and brain regions associated with MDD, indicating that genes traditionally linked to neuronal pathways are also expressed in immune cells, where they may contribute to immune-related mechanisms relevant to the disorder. These findings highlight potential systemic molecular patterns that warrant further investigation.

BACKGROUND: Metal exposure is a hypothesized risk factor for chronic kidney disease of uncertain etiology, an ongoing epidemic in Central America, yet metal biomonitoring data in this region are scant.

METHODS: We measured metal toenail concentrations using inductively coupled plasma mass spectrometry and calculated estimated glomerular filtration rate (eGFR) in a cohort of Nicaraguans 14-31 years (n = 297; 49% female; data collected in 2023). We used multivariable linear and ordinal regression and Bayesian kernel machine regression to examine individual element and mixture associations of arsenic, cadmium, mercury, nickel, lead, and uranium with eGFR.

RESULTS: The middle tertile of nickel was associated with -6.92 ml/min/1.73 m2 reduction in eGFR (95% confidence intervals [CI] = -10.7, -3.12) compared to the lowest tertile, suggesting a "U-shaped" association. The highest tertile of arsenic was associated with -4.25 ml/min/1.73 m2 eGFR reduction (95% CI = -8.42, -0.07) compared to the lowest tertile. Associations between other metals and eGFR were not detected. We observed no evidence of higher-order interactions or joint effects of the metal mixture on eGFR.

CONCLUSIONS: In this sample of young people in a high-chronic kidney disease of uncertain etiology-risk region, nickel and arsenic were independently associated with reduced eGFR, but other metals and their mixture were not. This finding supports targeted metals biomonitoring and source investigation.