Rationale: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55–68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57–69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19–0.92]; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15–0.89]; P =0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12–0.70]; P =0.01) in patients with COVID-19 and coexisting hypertension. Conclusions: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

Laser Speckle Contrast Imaging (LSCI) is a minimally invasive full field optical technique used to generate blood flow maps with high spatial and temporal resolution. The lack of quantitative accuracy and the inability to predict flows in the presence of static scatterers such as an intact or thinned skull have been the primary limitation of LSCI. We present a new Multi-Exposure Speckle Imaging (MESI) instrument that has potential to obtain quantitative baseline flow measures. We show that the MESI instrument extends the range over which relative flow measurements are linear. We also present a new speckle model which can discriminate flows in the presence of static scatters. We show that in the presence of static scatterers the new model used along with the new MESI instrument can predict correlation times of flow consistently to within 10% of the value without static scatterers compared to an average deviation of more than 100% from the value without static scatterers using traditional LSCI. We also show that the new speckle model used with the MESI instrument can maintain the linearity of relative flow measurements in the presence of static scatterers.

Screening for circulating tumor cells (CTCs) in blood has been an object of interest for evidence of progressive disease, status of disease activity, recognition of clonal evolution of molecular changes and for possible early diagnosis of cancer. We describe a new method of microchip-based immunomagnetic CTC detection, in which the benefits of both immunomagnetic assay and the microfluidic device are combined. As the blood sample flows through the microchannel closely above arrayed magnets, cancer cells labeled with magnetic nanoparticles are separated from blood flow and deposited at the bottom wall of the glass coverslip, which allows direct observation of captured cells with a fluorescence microscope. A polydimethylsiloxane (PDMS)-based microchannel fixed on a glass coverslip was used to screen blood samples. The thin, flat dimensions of the microchannel, combined with the sharp magnetic field gradient in the vicinity of arrayed magnets with alternate polarities, lead to an effective capture of labeled cells. Comparing to the commercially available CellSearch™ system, less (25%) magnetic particles are required to achieve a comparable capture rate, while the screening speed (at optimal blood flow rate of 10 mL/hour) is more than five times faster than those reported previously with a microchannel-based assay. For the screening experiment, blood drawn from healthy subjects into CellSave™ tubes was spiked with cultured cancer cell lines of COLO205 and SKBR3. The blood was then kept at room temperature for 48 hours before the screening, emulating the actual clinical cases of blood screening. Customized Fe3O4 magnetic nanoparticles (Veridex Ferrofluid™) conjugated to anti-Epithelial cell adhesion molecule (EpCAM) antibodies were introduced into the blood samples to label cancer cells, and the blood was then run through the microchip device to capture the labelled cells. After capture, the cells were stained with fluorescently labelled anti-cytokeratin, DAPI and anti-CD45. Subsequent immunofluorescence images were taken for the captured cells, followed by comprehensive computer aided analysis based on fluorescence intensities and cell morphology. Rare cancer cells (from ~1000 cells down to ~5 cells per mL) with very low tumor cell to blood cell ratios (about 1: 107~109, including red blood cells) were successfully detected. Cancer cell capture rates of 90% and 86% were demonstrated for COLO205 and SKBR3cells, respectively.

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SummaryEpigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling. However, the underlying regulatory mechanism remains to be elucidated. Here we identified a heart-enriched long non-coding (lnc)RNA, named Cardiac Hypertrophy Associated Epigenetic Regulator (Chaer), necessary for the development of cardiac hypertrophy. Mechanistically, Chaer directly interacts with Polycomb Repressor Complex 2 (PRC2) catalytic subunit through a 66-mer motif, interferes with its targeting to genomic locus, and subsequently inhibits histone H3 lysine 27 methylation at hypertrophic genes. This interaction is transiently induced upon hormone or stress stimulation in an mTORC1 dependent manner, and is prerequisite for epigenetic reprogramming and induction of hypertrophic genes. Inhibition of Chaer in intact heart before, but not after, the onset of pressure overload significantly attenuates cardiac hypertrophy and dysfunction. Therefore, our study reveals that stress-induced pathological gene activation in heart requires a previously uncharacterized lncRNA-dependent epigenetic checkpoint.