Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs.

Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we develop a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method reveals a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and CD8 T cells, is found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings offer further insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis.

Mass cytometry as a tool in target validation and drug discovery.

Mass cytometry provides highly multiparametric data at a single cell level, coupling the specificity and sensitivity of time-of-flight mass spectrometry with the single-cell throughput of flow cytometry. It offers great value in interrogating the potentially heterogenous impact that a drug may have on a biological system, allowing an investigator to capture not just changes in cell behavior, but how these changes may differ between cell subtypes. In this chapter, we review the technical details of the platform as well as its limitations, before describing our approach to planning and running a mass cytometry experiment. A series of method modules, spanning the staining process through to data cleaning, are described that are then combined to create three separate experiments. The first experiment illustrates a core process in mass cytometry: the validation and titration of a metal-conjugated antibody reporter. The second experiment explores the impact of a kinase inhibitor on cell cycle and apoptosis pathways of a human myeloma cell line. And the third experiment exploits the multiparametric capability of mass cytometry, by exploring the differential expression changes in a transcription factor upon drug treatment across the cellular compartments of a peripheral blood mononuclear cell sample.

Digitally Assisted Peer Recovery Coach to Facilitate Linkage to Outpatient Treatment Following Inpatient Alcohol Withdrawal Treatment: Proof-of-Concept Pilot Study.

BACKGROUND: Alcohol use disorder (AUD), associated with significant morbidity and mortality, continues to be a major public health problem. The COVID-19 pandemic exacerbated the impact of AUD, with a 25% increase in alcohol-related mortality from 2019 to 2020. Thus, innovative treatments for AUD are urgently needed. While inpatient alcohol withdrawal management (detoxification) is often an entry point for recovery, most do not successfully link to ongoing treatment. Transitions between inpatient and outpatient treatment pose many challenges to successful treatment continuation. Peer recovery coaches-individuals with the lived experience of recovery who obtain training to be coaches-are increasingly used to assist individuals with AUD and may provide a degree of continuity during this transition. OBJECTIVE: We aimed to evaluate the feasibility of using an existing care coordination app (Lifeguard) to assist peer recovery coaches in supporting patients after discharge and facilitating linkage to care. METHODS: This study was conducted on an American Society of Addiction Medicine-Level IV inpatient withdrawal management unit within an academic medical center in Boston, MA. After providing informed consent, participants were contacted by the coach through the app, and after discharge, received daily prompts to complete a modified version of the brief addiction monitor (BAM). The BAM inquired about alcohol use, risky, and protective factors. The coach sent daily motivational texts and appointment reminders and checked in if BAM responses were concerning. Postdischarge follow-up continued for 30 days. The following feasibility outcomes were evaluated: (1) proportion of participants engaging with the coach before discharge, (2) proportion of participants and the number of days engaging with the coach after discharge, (3) proportion of participants and the number of days responding to BAM prompts, and (4) proportion of participants successfully linking with addiction treatment by 30-day follow-up. RESULTS: All 10 participants were men, averaged 50.5 years old, and were mostly White (n=6), non-Hispanic (n=9), and single (n=8). Overall, 8 participants successfully engaged with the coach prior to discharge. Following discharge, 6 participants continued to engage with the coach, doing so on an average of 5.3 days (SD 7.3, range 0-20 days); 5 participants responded to the BAM prompts during the follow-up, doing so on an average of 4.6 days (SD 6.9, range 0-21 days). Half (n=5) successfully linked with ongoing addiction treatment during the follow-up. The participants who engaged with the coach post discharge, compared to those who did not, were significantly more likely to link with treatment (83% vs 0%, χ2=6.67, P=.01). CONCLUSIONS: The results demonstrated that a digitally assisted peer recovery coach may be feasible in facilitating linkage to care following discharge from inpatient withdrawal management treatment. Further research is warranted to evaluate the potential role for peer recovery coaches in improving postdischarge outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05393544; https://www.clinicaltrials.gov/ct2/show/NCT05393544.

Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages' transition into a pro-inflammatory state.

AIMS: CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. METHOD AND RESULTS: Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe-/- background were generated (CD40wt and CD40mac-/-, respectively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac-/- compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac-/- atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b- macrophages in the atherosclerotic aorta of CD40mac-/- compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac-/- mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). CONCLUSIONS: We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.

Designing a Framework for Remote Cancer Care Through Community Co-design: Participatory Development Study.

BACKGROUND: Recent shifts to telemedicine and remote patient monitoring demonstrate the potential for new technology to transform health systems; yet, methods to design for inclusion and resilience are lacking. OBJECTIVE: The aim of this study is to design and implement a participatory framework to produce effective health care solutions through co-design with diverse stakeholders. METHODS: We developed a design framework to cocreate solutions to locally prioritized health and communication problems focused on cancer care. The framework is premised on the framing and discovery of problems through community engagement and lead-user innovation with the hypothesis that diversity and inclusion in the co-design process generate more innovative and resilient solutions. Discovery, design, and development were implemented through structured phases with design studios at various locations in urban and rural Kentucky, including Appalachia, each building from prior work. In the final design studio, working prototypes were developed and tested. Outputs were assessed using the System Usability Scale as well as semistructured user feedback. RESULTS: We co-designed, developed, and tested a mobile app (myPath) and service model for distress surveillance and cancer care coordination following the LAUNCH (Linking and Amplifying User-Centered Networks through Connected Health) framework. The problem of awareness, navigation, and communication through cancer care was selected by the community after framing areas for opportunity based on significant geographic disparities in cancer and health burden resource and broadband access. The codeveloped digital myPath app showed the highest perceived combined usability (mean 81.9, SD 15.2) compared with the current gold standard of distress management for patients with cancer, the paper-based National Comprehensive Cancer Network Distress Thermometer (mean 74.2, SD 15.8). Testing of the System Usability Scale subscales showed that the myPath app had significantly better usability than the paper Distress Thermometer (t63=2.611; P=.01), whereas learnability did not differ between the instruments (t63=-0.311; P=.76). Notable differences by patient and provider scoring and feedback were found. CONCLUSIONS: Participatory problem definition and community-based co-design, design-with methods, may produce more acceptable and effective solutions than traditional design-for approaches.

Emerging digital technologies in cancer treatment, prevention, and control.

The very first issue of the journal of Translational Behavioral Medicine (TBM) was dedicated, in part, to the theme of Health Information Technology as a platform for evidence implementation. The topic was timely: legislation in the USA was passed with the intent of stimulating the adoption of electronic health records; mobile smartphones, tablets, and other devices were gaining traction in the consumer market, while members within the Society of Behavioral Medicine were gaining scientific understanding on how to use these tools to effect healthy behavior change. For the anniversary issue of TBM, we evaluated the progress and problems associated with deploying digital health technologies to support cancer treatment, prevention, and control over the last decade. We conducted a narrative review of published literature to identify the role that emerging digital technologies may take in achieving national and international objectives in the decade to come. We tracked our evaluation of the literature across three phases in the cancer control continuum: (a) prevention, (b) early detection/screening, and (c) treatment/survivorship. From our targeted review and analyses, we noted that significant progress had been made in the adoption of digital health technologies in the cancer space over the past decade but that significant work remains to be done to integrate these technologies effectively into the cancer control systems needed to improve outcomes equitably across populations. The challenge for the next 10 years is inherently translational.

Differential Treatment Response Between Hypochondriasis With and Without Prominent Somatic Symptoms.

Background: Health anxiety may exist with or without prominent somatic symptoms, but the impact of somatic symptoms on treatment response is unclear. The study objective was to examine this question further as symptom burden may impact choice of type of treatment. Methods: This exploratory study used a unique database from a prior trial of 193 individuals with DSM-IV hypochondriasis who had been randomly assigned to either cognitive behavioral therapy, fluoxetine, combined therapy, or placebo. Two subgroups were newly defined-no/low somatic burden (n = 42) and prominent somatic burden (n = 151). Response was defined by ≥30% improvement in hypochondriasis. Results: Among high somatic hypochondriacal participants, compared to placebo, the odds of being a responder were significantly greater among those who received fluoxetine, either alone (OR = 4.46; 95% CI: 1.38, 14.41) or with cognitive behavioral therapy (OR = 3.56; 95% CI: 1.19, 10.68); the estimated odds were not significantly different for those receiving cognitive behavioral therapy alone (OR = 1.81; 95% CI: 0.59, 5.54). In contrast, among low somatic hypochondriacal participants, compared to placebo, the observed odds of being a responder were similar in magnitude and direction for those who received cognitive behavioral therapy, either alone (OR = 3.00; 95% CI: 0.38, 23.68) or in combination with fluoxetine (OR = 3.60; 95% CI: 0.62, 21.03), compared to the odds for those receiving fluoxetine alone (OR = 0.90; 95% CI: 0.14, 5.65). High somatic hypochondriacal individuals assigned to any fluoxetine group had significantly greater odds of being a responder than those who had not received fluoxetine (OR = 2.70; 95% CI: 1.33, 5.48). Low somatic hypochondriacal individuals assigned to any cognitive behavioral therapy group had significantly greater odds of being a responder than those who had not received cognitive behavioral therapy (OR = 8.03; 95% CI: 1.41, 45.67). Conclusion: These findings indicate that somatic symptom burden may be important in guiding treatment selection among individuals with marked health anxiety, as hypochondriacal individuals with high somatic burden responded more often to fluoxetine while those with low somatic burden responded more often to cognitive behavioral therapy. Systematic replication with larger studies is needed.

Metabolic requirements of NK cells during the acute response against retroviral infection.

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2.

Activated Regulatory T-Cells, Dysfunctional and Senescent T-Cells Hinder the Immunity in Pancreatic Cancer.

Pancreatic cancer has one of the worst prognoses of any human malignancy and leukocyte infiltration is a major prognostic marker of the disease. As current immunotherapies confer negligible survival benefits, there is a need to better characterise leukocytes in pancreatic cancer to identify better therapeutic strategies. In this study, we analysed 32 human pancreatic cancer patients from two independent cohorts. A multi-parameter mass-cytometry analysis was performed on 32,000 T-cells from eight patients. Single-cell RNA sequencing dataset analysis was performed on a cohort of 24 patients. Multiplex immunohistochemistry imaging and spatial analysis were performed to map immune infiltration into the tumour microenvironment. Regulatory T-cell populations demonstrated highly immunosuppressive states with high TIGIT, ICOS and CD39 expression. CD8+ T-cells were found to be either in senescence or an exhausted state. The exhausted CD8 T-cells had low PD-1 expression but high TIGIT and CD39 expression. These findings were corroborated in an independent pancreatic cancer single-cell RNA dataset. These data suggest that T-cells are major players in the suppressive microenvironment of pancreatic cancer. Our work identifies multiple novel therapeutic targets that should form the basis for rational design of a new generation of clinical trials in pancreatic ductal adenocarcinoma.

Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.

BACKGROUND: How specific nutrients influence adaptive immunity is of broad interest. Iron deficiency is the most common micronutrient deficiency worldwide and imparts a significant burden of global disease; however, its effects on immunity remain unclear. METHODS: We used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells in vitro and on immune responses to vaccines and viral infection in mice. We examined humoral immunity in human patients with raised hepcidin and low serum iron caused by mutant TMPRSS6. We tested the effect of iron supplementation on vaccination-induced humoral immunity in piglets, a natural model of iron deficiency. FINDINGS: We show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of activated lymphocytes requires the support of enhanced iron acquisition, which is facilitated by IRP1/2 and TFRC. Accordingly, providing extra iron improved the response to vaccination in hypoferremic mice and piglets, while conversely, hypoferremic humans with chronically increased hepcidin have reduced concentrations of antibodies specific for certain pathogens. Imposing hypoferremia blunted the T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist and exacerbating lung inflammation and morbidity. CONCLUSIONS: Hypoferremia, a well-conserved physiological innate response to infection, can counteract the development of adaptive immunity. This nutrient trade-off is relevant for understanding and improving immune responses to infections and vaccines in the globally common contexts of iron deficiency and inflammatory disorders. FUNDING: Medical Research Council, UK.

Behavior-based diabetes management: impact on care, hospitalizations, and costs.

OBJECTIVES: To (1) examine the impact of the Diabetes Care Rewards (DCR) program on adherence to care standards and (2) evaluate the economic impact of adherence to care standards. STUDY DESIGN: A retrospective observational cohort study design with propensity matching. Additional covariates adjustment was used to minimize residual imbalance. METHODS: Utilization and cost data were compared between individuals enrolled vs individuals eligible for but not enrolled in the DCR program using a standard mean difference. Individuals were employees or their dependents from self-insured companies throughout the United States. Outcomes included adherence to the care standards, service utilization, and costs. RESULTS: A total of 3318 propensity-matched participants were included. Primary analysis revealed that enrolled members increased adherence to semiannual glycated hemoglobin, annual lipid, and annual urine albumin-creatinine ratio testing. Additionally, enrolled members experienced less utilization of high-acuity services and increased rates of physician visits. In a secondary analysis, the enrolled group was associated with greater pharmaceutical costs but lower medical costs. CONCLUSIONS: A behavioral science- and incentive-based diabetes management program was associated with greater rates of adherence to recommended diabetes monitoring care standards, increased routine clinic visits, decreased hospital admissions, and decreased inpatient days. Anticipated increases in pharmaceutical expenditures were offset by overall lower medical expenditures. Results indicate the economic benefits of adherence to evidence-based standards for diabetes care.

Digital Phenotyping to Enhance Substance Use Treatment During the COVID-19 Pandemic.

Due to the COVID-19 pandemic, many clinical addiction treatment programs have been required to transition to telephonic or virtual visits. Novel solutions are needed to enhance substance use treatment during a time when many patients are disconnected from clinical care and social support. Digital phenotyping, which leverages the unique functionality of smartphone sensors (GPS, social behavior, and typing patterns), can buttress clinical treatment in a remote, scalable fashion. Specifically, digital phenotyping has the potential to improve relapse prediction and intervention, relapse detection, and overdose intervention. Digital phenotyping may enhance relapse prediction through coupling machine learning algorithms with the enormous amount of collected behavioral data. Activity-based analysis in real time can potentially be used to prevent relapse by warning substance users when they approach locational triggers such as bars or liquor stores. Wearable devices detect when a person has relapsed to substances through measuring physiological changes such as electrodermal activity and locomotion. Despite the initial promise of this approach, privacy, security, and barriers to access are important issues to address.

ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies.

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.

Mending Disconnects in Cancer Care: Setting an Agenda for Research, Practice, and Policy.

Cancer in the United States accounts for $600 billion in health care costs, lost work time and productivity, reduced quality of life, and premature mortality. The future of oncology delivery must mend disconnects to equitably improve patient outcomes while constraining costs and burden on patients, caregivers, and care teams. Embedding learning health systems into oncology can connect care, engaging patients and providers in fully interoperable data systems that remotely monitor patients; generate predictive and prescriptive analytics to facilitate appropriate, timely referrals; and extend the reach of clinicians beyond clinic walls. Incorporating functional learning systems into the future of oncology and follow-up care requires coordinated national attention to 4 synergistic strategies: (1) galvanize and shape public discourse to develop and adopt these systems, (2) demonstrate their value, (3) test and evaluate their use, and (4) reform policy to incentivize and regulate their use.

Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism.

T helper (Th) cells are CD4+ effector T cells that play a critical role in immunity by shaping the inflammatory cytokine environment in a variety of physiological and pathological situations. Using a combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A and KDM6B as central regulators of human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels of the repressive H3K27me3 chromatin mark and leads to suppression of the key transcription factor RORγt during Th17 differentiation. In mature Th17 cells, GSK-J4 induces an altered transcriptional program with a profound metabolic reprogramming and concomitant suppression of IL-17 cytokine levels and reduced proliferation. Single-cell analysis reveals a specific shift from highly inflammatory cell subsets toward a resting state upon demethylase inhibition. The root cause of the observed antiinflammatory phenotype in stimulated Th17 cells is reduced expression of key metabolic transcription factors, such as PPRC1. Overall, this leads to reduced mitochondrial biogenesis, resulting in a metabolic switch with concomitant antiinflammatory effects. These data are consistent with an effect of GSK-J4 on Th17 T cell differentiation pathways directly related to proliferation and include regulation of effector cytokine profiles. This suggests that inhibiting KDM6 demethylases may be an effective, even in the short term, therapeutic target for autoimmune diseases, including ankylosing spondylitis.

Olfactory and Neuropsychological Functioning in Olfactory Reference Syndrome.

BACKGROUND: Olfactory reference syndrome (ORS) is an underrecognized, understudied, and often severe psychiatric disorder characterized by a prominent and distressing or impairing preoccupation with a false belief of emitting an offensive body odor. As this condition has only recently been recognized in the International Classification of Diseases (the 11th Edition), no empirical evidence exists about the underlying features and etiology of the disorder. OBJECTIVE: To examine the neuropsychological and olfactory functioning of individuals with ORS and address whether there is central nervous system or sensory dysfunction associated with the condition. METHODS: In this preliminary investigation, 9 consecutive participants with ORS completed a structured clinical interview and neuropsychological and olfaction evaluations. RESULTS: A proportion of individuals with ORS displayed deficits in aspects of cognitive functioning (i.e., processing speed, executive functioning, recognition memory bias for ORS-related words), olfaction functioning (i.e., odor detection and discrimination), and emotional processing. CONCLUSIONS: Based on these preliminary findings of cognitive, olfaction, and emotional processing deficits in individuals with ORS, further neuropsychological and olfaction studies are needed that better characterize this understudied patient group and address this study's limitations.

Barn-Raising on the Digital Frontier: The L.A.U.N.C.H. Collaborative.

A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches-or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond the clinic-are becoming an indispensable tool in medicine to overcome the obstacle of distance.

The Landscape of Connected Cancer Symptom Management in Rural America: A Narrative Review of Opportunities for Launching Connected Health Interventions.

Background: The 2016 President's Cancer Panel called for projects focusing on improving cancer symptom management using connected health technologies (broadband and telecommunications). However, rural communities, like those in Appalachia, may experience a "double burden" of high cancer rates and lower rates of broadband access and adoption necessary for connected health solutions. Purpose: To better understand the current landscape of connected health in the management of cancer symptoms in rural America. Methods: A literature search was conducted using four academic databases (PubMed, CINAHL, MEDLINE, and PsycINFO) to locate articles published from 2010 to 2019 relevant to connected cancer symptom management in rural America. Text screening was conducted to identify relevant publications. Results: Among 17 reviewed studies, four were conducted using a randomized controlled trial; the remainder were formative in design or small pilot projects. Five studies engaged stakeholders from rural communities in designing solutions. Most commonly studied symptoms were psychological/emotional symptoms, followed by physical symptoms, particularly pain. Technologies used were primarily telephone-based; few were Internet-enabled video conferencing or web-based. Advanced mobile and Internet-based approaches were generally in the development phase. Overall, both rural patients and healthcare providers reported high acceptance, usage, and satisfaction of connected health technologies. Ten of the 17 studies reported improved symptom management outcomes. Methodological challenges that limited the interpretation of the findings were summarized. Implications: The review identified a need to engage rural stakeholders to develop and test connected cancer symptom management solutions that are based on advanced mobile and broadband Internet technologies.

Experiencing Cancer in Appalachian Kentucky.

Quilted Appalachian Sunset©2011 Jim Harrisjim-harris.pixels.com Nothing tells the story of people working together better than a community quilt. A diversity of talents, colors, and materials brought together through skill and shared purpose. Perhaps never before have we as Americans needed a stronger reminder that many hands make short work of big problems. The work presented here by the L.A.U.N.C.H. Collaborative offers a new framework for health care that could be compared to a digital quilt, powered by community-based participatory design, with lived expertise and the newest advances in broadband-enabled connected health solutions. This work demonstrates the value and need to engage local communities and what can be learned when beneficiaries and traditional caregivers work together to develop healthcare solutions.