Bioinspired, nanoscale approaches in contemporary bioanalytics (Review)

The genesis for this topical review stems from the interdisciplinary Biointerfaces International conference 2016 (BI 2016) in Zurich, Switzerland, wherein the need for advances in analytical tools was both expressed and addressed. Pushing the limits of detection for characterizing individual components, such as single proteins, single drug-delivery vehicles, or probing single living cells in a more natural environment, will contribute to the understanding of the complex biomolecular systems central to a number of applications including medical diagnostics, tissue engineering, and drug screening and delivery. Accordingly, the authors begin with an overview of single nanoparticle analytics highlighting two emerging techniques and how they compare with existing techniques. The first is based on single particle tracking of nanoparticles tethered to a mobile supported lipid bilayer, enabling the simultaneous characterization of both size and composition of individual nanoparticles. The second technique is based on probing variations in the ionic conduction across nanoscale apertures for detection of not only nanoparticles but also membrane-tethered proteins, thereby allowing a multiparameter characterization of individual nanoscopic objects, addressing their size, shape, charge, and dipole moment. Subsequently, the authors lead into an example of an area of application that stands to benefit from such advances in bioanalytics, namely, the development of biomimetic lipid- and polymer-based assemblies as stimuli-responsive artificial organelles and nanocarriers designed to optimize delivery of next generation high-molecular-weight biological drugs. This in turn motivates the need for additional advanced techniques for investigating the cellular response to drug delivery, and so the review returns again to bioanalytics, in this case single-cell analysis, while highlighting a technique capable of probing and manipulating the content of individual living cells via fluidic force microscopy. In presenting a concerted movement in the field of bioinspired bioanalytics, positioned in the context of drug delivery, while also noting the critical role of surface modifications, it is the authors’ aim to evaluate progress in the field of single component bioanalytics and to emphasize the impact of initiating and maintaining a fruitful dialogue among scientists, together with clinicians and industry, to guide future directions in this area and to steer innovation to successful translation

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

The value of open-source clinical science in pandemic response: lessons from ISARIC

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