Intensive Care and Organ Support Related Mortality in Patients With COVID-19: A Systematic Review and Meta-Analysis.

To perform a systematic review and meta-analysis to generate estimates of mortality in patients with COVID-19 that required hospitalization, ICU admission, and organ support. DATA SOURCES: A systematic search of PubMed, Embase, and the Cochrane databases was conducted up to December 31, 2021. STUDY SELECTION: Previously peer-reviewed observational studies that reported ICU, mechanical ventilation (MV), renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO)-related mortality among greater than or equal to 100 individual patients. DATA EXTRACTION: Random-effects meta-analysis was used to generate pooled estimates of case fatality rates (CFRs) for in-hospital, ICU, MV, RRT, and ECMO-related mortality. ICU-related mortality was additionally analyzed by the study country of origin. Sensitivity analyses of CFR were assessed based on completeness of follow-up data, by year, and when only studies judged to be of high quality were included. DATA SYNTHESIS: One hundred fifty-seven studies evaluating 948,309 patients were included. The CFR for in-hospital mortality, ICU mortality, MV, RRT, and ECMO were 25.9% (95% CI: 24.0-27.8%), 37.3% (95% CI: 34.6-40.1%), 51.6% (95% CI: 46.1-57.0%), 66.1% (95% CI: 59.7-72.2%), and 58.0% (95% CI: 46.9-68.9%), respectively. MV (52.7%, 95% CI: 47.5-58.0% vs 31.3%, 95% CI: 16.1-48.9%; p = 0.023) and RRT-related mortality (66.7%, 95% CI: 60.1-73.0% vs 50.3%, 95% CI: 42.4-58.2%; p = 0.003) decreased from 2020 to 2021. CONCLUSIONS: We present updated estimates of CFR for patients hospitalized and requiring intensive care for the management of COVID-19. Although mortality remain high and varies considerably worldwide, we found the CFR in patients supported with MV significantly improved since 2020.

Electrophoretic Deposition of Nanocrystalline Calcium Phosphate Coating for Augmenting Bioactivity of Additively Manufactured Ti-6Al-4V.

Additive manufacturing (AM) is being widely explored for engineering biomedical implants. The microstructure and surface finish of additively manufactured parts are typically different from wrought parts and exhibit limited bioactivity despite the other advantages of using AM for fabrication. The aim of this study was to enhance the bioactivity of selective laser melted Ti-6Al-4V alloy by electrophoretic deposition of nanohydroxyapatite (nanoHAp) coatings. The deposition parameters were systematically investigated after the coatings were deposited on the as-manufactured surface or after polishing the surface of the additively-manufactured sample. The surfaces were coated with nanoHAp suspended in either ethanol or butanol using different voltages (10, 30, or 50 V) for varied deposition times. The formation of the nanoHAp coating was confirmed by Fourier-transform infrared spectroscopy and X-ray diffraction. Microstructural analysis revealed that several conditions of the coating led to crack formation. The coated samples were subsequently heat-treated to improve the integrity of the coating. Heat treatment led to crack formation in several conditions due to thermal shrinkages. Coatings prepared using butanol were more uniform and had minimal cracks compared with the use of ethanol. Nanoindentation confirmed good stability and integrity of the nanoHAP coatings on the as-manufactured and polished surfaces. The coating on the as-manufactured sample exhibited higher hardness and lower elastic modulus as compared with the coating on the polished sample. In vitro study revealed that the nanoHAp coating markedly enhanced the attachment, proliferation, and differentiation of preosteoblasts on the alloy. These results provide a viable route to enhancing the bioactivity through deposition of nanoHAp with important implications for engineering additively manufactured orthopedic and dental implants suitable for better clinical performance.

Myosin-Specific Adaptations of In vitro Fluorescence Microscopy-Based Motility Assays.

Myosin proteins bind and interact with filamentous actin (F-actin) and are found in organisms across the phylogenetic tree. Their structure and enzymatic properties are adapted for the particular function they execute in cells. Myosin 5a processively walks on F-actin to transport melanosomes and vesicles in cells. Conversely, nonmuscle myosin 2b operates as a bipolar filament containing approximately 30 molecules. It moves F-actin of opposite polarity toward the center of the filament, where the myosin molecules work asynchronously to bind actin, impart a power stroke, and dissociate before repeating the cycle. Nonmuscle myosin 2b, along with its other nonmuscle myosin 2 isoforms, has roles that include cell adhesion, cytokinesis, and tension maintenance. The mechanochemistry of myosins can be studied by performing in vitro motility assays using purified proteins. In the gliding actin filament assay, the myosins are bound to a microscope coverslip surface and translocate fluorescently labeled F-actin, which can be tracked. In the single molecule/ensemble motility assay, however, F-actin is bound to a coverslip and the movement of fluorescently labeled myosin molecules on the F-actin is observed. In this report, the purification of recombinant myosin 5a from Sf9 cells using affinity chromatography is outlined. Following this, we outline two fluorescence microscopy-based assays: the gliding actin filament assay and the inverted motility assay. From these assays, parameters such as actin translocation velocities and single molecule run lengths and velocities can be extracted using the image analysis software. These techniques can also be applied to study the movement of single filaments of the nonmuscle myosin 2 isoforms, discussed herein in the context of nonmuscle myosin 2b. This workflow represents a protocol and a set of quantitative tools that can be used to study the single molecule and ensemble dynamics of nonmuscle myosins.

A Pulse Wave Velocity Based Method to Assess the Mean Arterial Blood Pressure Limits of Autoregulation in Peripheral Arteries.

Background: Constant blood flow despite changes in blood pressure, a phenomenon called autoregulation, has been demonstrated for various organ systems. We hypothesized that by changing hydrostatic pressures in peripheral arteries, we can establish these limits of autoregulation in peripheral arteries based on local pulse wave velocity (PWV). Methods: Electrocardiogram and plethysmograph waveforms were recorded at the left and right index fingers in 18 healthy volunteers. Each subject changed their left arm position, keeping the right arm stationary. Pulse arrival times (PAT) at both fingers were measured and used to calculate PWV. We calculated ΔPAT (ΔPWV), the differences between the left and right PATs (PWVs), and compared them to the respective calculated blood pressure at the left index fingertip to derive the limits of autoregulation. Results: ΔPAT decreased and ΔPWV increased exponentially at low blood pressures in the fingertip up to a blood pressure of 70 mmHg, after which changes in ΔPAT and ΔPWV were minimal. The empirically chosen 20 mmHg window (75-95 mmHg) was confirmed to be within the autoregulatory limit (slope = 0.097, p = 0.56). ΔPAT and ΔPWV within a 20 mmHg moving window were not significantly different from the respective data points within the control 75-95 mmHg window when the pressure at the fingertip was between 56 and 110 mmHg for ΔPAT and between 57 and 112 mmHg for ΔPWV. Conclusions: Changes in hydrostatic pressure due to changes in arm position significantly affect peripheral arterial stiffness as assessed by ΔPAT and ΔPWV, allowing us to estimate peripheral autoregulation limits based on PWV.