Nothing About Us Without Us: Involving Youth Living With HIV in a Virtual Advisory Board.

PURPOSE: We adapted a traditional community advisory board to the needs of youth living with HIV (YLWH), resulting in a virtual, asynchronous, and anonymous youth advisory board (YAB). The YAB's evolution fostered participation during the adaptation of an HIV care mobile health application. METHODS: YAB members, comprised of YLWH in South Texas, engaged in the mobile application's formative evaluation, adaptation, and pilot implementation. We collected feedback via surveys and interviews, analyzed and integrated responses, tracked participation and YAB adaptations, and performed content analysis. RESULTS: Driven by feedback, the YAB evolved from in-person group meetings to the current iteration. We administered five surveys, and YAB members provided feedback on communication preferences; mobile app elements; privacy and confidentiality; and virtual support groups. DISCUSSION: Our adaptive process highlights three primary drivers of innovation: COVID-19 risk reduction, asynchrony, anonymity. Our success in maintaining YAB engagement suggests the adapted model could be employed to support youth input in other contexts.

Disproportionate Burden of COVID-19 Infection Among Hispanic Patients During the First COVID-19 Surge in South Texas.

Introduction: The morbidity and mortality of the COVID-19 pandemic have disproportionately burdened Hispanic populations in the United States. While health equity research is typically conducted in populations where Hispanics are the minority, this project analyzes COVID-19 racioethnic transmission trends over the first 6 months of the pandemic within a large majority-minority city in South Texas. Methods: Patients diagnosed with COVID-19 across inpatient, emergency department, and outpatient settings of a large county health system were included in a clinical registry. For 4644 COVID-19-positive patients between March 16 and August 31, 2020, demographic and clinical data were abstracted from the registry. Race/ethnicity trends over time were compared for patients with and without COVID-19 diagnoses. Logistic regressions identified predictors of inpatient diagnosis by age, race/ethnicity, and testing delay. Results: The proportion of patients with COVID-19 identifying as Hispanic increased rapidly during the pandemic's first months: from 55.6% in March to 85.7% in June. A significantly greater proportion of patients identified as Hispanic within the COVID-19 cohort compared to other diagnoses cohort. Testing delay was 11.6% longer for Hispanic patients, with each day of testing delay associated with 7% increased odds of inpatient COVID-19 diagnosis. Conclusion: These findings highlight the disproportionate impact of COVID-19 on Hispanic populations even within a majority-minority community. In the United States, Hispanic persons are more likely to work frontline jobs, live in multigenerational homes in poverty, and be uninsured. The burden of COVID-19 cases within Bexar County's largest hospital system reflects this systemic inequity. Identifying racioethnic health disparities supports efforts toward mitigating structural factors that predispose minority groups to illness and death.

Pivotal Advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response.

Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors, indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with T helper cell type 2-dependent immune responses and that recruitment is a dynamic, ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial-restricted. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.

Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft.

BACKGROUND: Donor-specific tolerance (DST) is induced after allogeneic hematopoietic cell transplantation (HCT) and is a potential strategy for prolonging survival of solid organ grafts. DST may persist in recipients with transient mixed hematopoietic chimerism (MC) when solid organ transplantation and HCT are done concomitantly. METHODS: In a canine model of allogeneic HCT after nonmyeloablative conditioning, DST to skin grafts was evaluated in dog leukocyte antigen (DLA)-identical recipients with stable MC (n=11), or after rejection of the hematopoietic cell (HC) graft (n=19). RESULTS: There was significant improvement in the survival of DLA-identical HC donor-derived skin grafts in recipients with MC compared to normal recipients (n=7; P<0.0001). However, HC donor-derived skin grafts in four recipients with MC developed an inflammatory reaction without skin graft loss. This may represent partial DST. Survival of DLA-identical HC donor-derived skin grafts was also significantly prolonged compared to normal recipients even when skin grafting was delayed until after rejection of the HC graft (P=0.002). An inflammatory reaction developed in all nine of the surviving HC donor-derived skin grafts in this group, but there was no graft loss at last follow-up (median, 30 [range, 9-84] weeks). An increased time to rejection of the hematopoietic graft was associated with prolonged survival of the subsequent skin graft (P=0.02). CONCLUSION: In a model of stable MC, DST to skin grafts may be complete or partial. Partial DST can persist after HC graft rejection even if solid organ transplantation is delayed. Further investigations are required to understand the mechanisms responsible for DST after allogeneic HCT.

Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells.

The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.

Allergic pulmonary inflammation promotes the recruitment of circulating tumor cells to the lung.

Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well-understood mechanisms that mediate the movement of multiple cell types. The nonspecific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the i.v. injection of B16-F10 melanoma cells in mice. These studies showed that allergen-induced pulmonary inflammation resulted in a >3-fold increase in lung metastases. This increase was dependent on CD4(+) T-cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more Galpha(i)-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data show that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggest that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7% to 8% of breast cancer patients with this lung disease.

Eosinophils: singularly destructive effector cells or purveyors of immunoregulation?

Eosinophils are granulocytes typically associated with immune responses to a limited number of specific insults, including helminth infection and exposure to various allergens. Moreover, the overwhelming consensus from the literature is that eosinophils evolved as uniquely destructive leukocytes with cytotoxic activities as an adaptation for host defense. However, recent studies now suggest that the parochial caricature of eosinophils as effector cells with nonspecific killing abilities that evolved as a host defense mechanism against large nonphagotizable parasites is incomplete. A new paradigm has emerged describing eosinophils as initial responders to cell death/tissue damage that are a part of remodeling/repair processes and, more importantly, significant contributors to localized innate and acquired immune responses as well as systemic adaptive immunity. Significantly, this new paradigm does not preclude roles for eosinophils in host defense leading to tissue damage but instead suggests the equal importance of eosinophil-associated regulatory mechanisms modulating local tissue immune responses. The goal of this review is to summarize the data in support of this new paradigm. In turn, we believe that this expanded role provides a probable explanation for the presence of eosinophils in diverse disease settings such as asthma, allergy, cancer, transplant rejection, gastrointestinal inflammation, and viral or helminth infection.