Background Distinct monocyte subsets predict cardiovascular risk and contribute to heart failure progression in murine models but have not been examined in clinical acute decompensated heart failure (ADHF). Methods and Results Blood samples were obtained from 11 healthy controls (HC) and at admission and discharge in 19 ADHF patients. Serological markers of inflammation were assessed on admission and discharge. Monocyte populations were defined using flow cytometry for cell-surface expression of CD14 and CD16: CD14++CD16− (classical), CD14++CD16+ (intermediate), and CD14+CD16++ (non-classical). In ADHF patients, C-reactive protein (CRP) and IL-6 were higher compared with HC (both p<0.001), and decreased from admission to discharge (CRP: 12.1±10.1 to 8.6±8.4 mg/L, p=0.005; IL-6: 19.8±34.5 to 7.1±4.7 pg/ml, p=0.08). In ADHF patients, the admission proportion of CD14++CD16-monocytes was lower (68% vs. 85%, p< 0.001) and CD14++CD16+ (15% vs. 8%, p=0.002) and CD14+CD16++ (17% vs. 7%, p=0.07) monocytes higher compared with HC. Additionally, the proportion of CD14++CD16− monocytes increased (68% to 79%, p=0.04) and the CD14+CD16++ monocytes decreased (17% to 7%, p=0.049) between admission and discharge. Conclusions Following standard treatment of ADHF, the monocyte profile and circulating inflammatory markers shifts to more closely resemble those of HC, suggesting a resolving acute inflammatory state. Functional studies are warranted to understand how specific monocyte subsets and systemic inflammation may contribute to ADHF pathophysiology.

Histone deacetylase inhibitors (HDACi) are promising therapeutics for cancer. HDACi alter the epigenetic state of tumors and provide a unique approach to treat cancer. Although studies with HDACi have shown promise in some cancers, variable efficacy and off-target effects have limited their use. To overcome some of the challenges of traditional HDACi, we sought to use a tumor-specific dendrimer scaffold to deliver HDACi directly to cancer cells. Here we report the design and evaluation of tumor-specific dendrimer–HDACi conjugates. The HDACi was conjugated to the dendrimer using an ester linkage through its hydroxamic acid group, inactivating the HDACi until it is released from the dendrimer. Using a cancer cell model, we demonstrate the functionality of the tumor-specific dendrimer–HDACi conjugates. Furthermore, we demonstrate that unlike traditional HDACi, dendrimer–HDACi conjugates do not affect tumor-associated macrophages, a recently recognized mechanism through which drug resistance emerges. We anticipate that this new class of cell-specific epigenetic therapeutics will have tremendous potential in the treatment of cancer.

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ObjectivesIt is essential to engage learners in efforts aimed at dismantling racism and other contributors to health care disparities. Barriers to their involvement include limited access to data. The objective of our study was to create a data dashboard using an existing quality improvement (QI) infrastructure and provide resident access to data to facilitate exploratory analysis on disparities in emergency department (ED) patient care.MethodsFocusing on patient populations that have previously been shown in the literature to suffer significant disparities in the ED, we extracted outcomes across a variety of metrics already collected as part of routine ED operations. Using data visualization software, we developed an interactive dashboard for visual exploratory analyses.ResultsWe designed a dashboard for our resident learners with views that are flexible and allow user selected filters to view clinical outcomes by patient age, treatment area, and chief complaint. Learners were also allowed to select grouping and outcomes of interest to investigate questions and form new hypotheses of their choosing. Available dashboard views included summary counts view to assess ED visits over time by selectable group, a rooming and triage acuity view, time‐to‐event survival curve view, histogram and box plot views for continuous variables, a view to assess outcome variables by time of day of ED arrival, customizable contingency table views, and correspondence analysis.ConclusionsUtilizing an existing QI infrastructure, we developed a dashboard that provides a new perspective into commonly collected ED operations data to allow for the exploration of disparities in ED care that is accessible to learners. Future directions include using these data to refine hypotheses on ED disparities, understand root causes, develop interventions, and measure their impact.

Rapid profiling of signaling pathways has been a long sought after goal in biological sciences and clinical medicine. To understand these signaling pathways, their protein components must be profiled. The protein components of signaling pathways are typically profiled with protein immunoblotting. Protein immunoblotting is a powerful technique but has several limitations including the large sample requirements, high amounts of antibody, and limitations in assay throughput. To overcome some of these limitations, we have designed a microfluidic protein immunoblotting device to profile multiple signaling pathways simultaneously. We show the utility of this approach by profiling inflammatory signaling pathways (NFκB, JAK-STAT, and MAPK) in cell models and human samples. The microfluidic immunoblotting device can profile proteins and protein modifications with 5380-fold less antibody compared to traditional protein immunoblotting. Additionally, this microfluidic device interfaces with commonly available immunoblotting equipment, has the ability to multiplex, and is compatible with several protein detection methodologies. We anticipate that this microfluidic device will complement existing techniques and is well suited for life science applications.