Flexible large-area ultrasound arrays for medical applications made using embossed polymer structures.

With the huge progress in micro-electronics and artificial intelligence, the ultrasound probe has become the bottleneck in further adoption of ultrasound beyond the clinical setting (e.g. home and monitoring applications). Today, ultrasound transducers have a small aperture, are bulky, contain lead and are expensive to fabricate. Furthermore, they are rigid, which limits their integration into flexible skin patches. New ways to fabricate flexible ultrasound patches have therefore attracted much attention recently. First prototypes typically use the same lead-containing piezo-electric materials, and are made using micro-assembly of rigid active components on plastic or rubber-like substrates. We present an ultrasound transducer-on-foil technology based on thermal embossing of a piezoelectric polymer. High-quality two-dimensional ultrasound images of a tissue mimicking phantom are obtained. Mechanical flexibility and effective area scalability of the transducer are demonstrated by functional integration into an endoscope probe with a small radius of 3 mm and a large area (91.2×14 mm2) non-invasive blood pressure sensor.

Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning.

Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient's immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy.

Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection.

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.

Hydroxychloroquine treatment in European patients with lupus erythematosus: dosing, retinopathy screening and adherence.

BACKGROUND: Use of hydroxychloroquine (HCQ) is common in patients with lupus erythematosus. Long-term use (ie, ≥5 years) and high-dose HCQ (ie, >5 mg/kg/day) are both risk factors for developing HCQ retinopathy. Advances in our understanding of HCQ retinopathy have led to changes in the recommendations for HCQ dosing and retinopathy screening. The latest EULAR guidelines for the management of SLE recommend a maximum HCQ dose of 5 mg/kg/day and ophthalmological screening at baseline and annually after 5 years of HCQ treatment. OBJECTIVES: This study aimed to assess whether the EULAR guidelines are affecting HCQ prescription patterns and screening frequencies in Europe. Furthermore, we inventoried adherence to HCQ. RESULTS: The online questionnaire was completed by 2936 patients with systemic, cutaneous or juvenile lupus from 33 countries. The majority were female (86.5%) and diagnosed with SLE (81.2%). Among those taking HCQ, the median HCQ dose reported was 4.26 mg/kg/day. More than one-third of respondents (36.8%) exceeded the recommended maximal HCQ dose of 5 mg/kg/day. Baseline ophthalmological screening had been done in 857 out of 1017 respondents diagnosed in the past 10 years (84.3%). Of patients using HCQ ≥5 years, 69.2% reported yearly retinopathy screening. Lastly, 17.3% of patients reported that they skipped HCQ once a week or more often. CONCLUSION: The results of our study demonstrate that higher than recommended dosages of HCQ are prescribed to more than one-third of patients with lupus in Europe. Recent recommendations regarding screening for retinopathy are incompletely implemented.

A wireless portable physiology recorder for psychophysiology research based on a personal digital assistant.

Psychophysiology research is increasingly relying on portable instruments that can assess physiological responses during real-life situations at locations outside of research labs, such as at school, home, work, and outdoors. In this article, I report on the feasibility of a personal digital assistant-based portable physiology recording system with online signal graphing and wireless digital telemetry for psychophysiology research. I demonstrate that such a system can measure electrocardiogram and electrodermal activity and send this data over a wireless communication link to a PC. It enables users to inspect the integrity of the acquired signals on the portable device and on a PC base station, and it allows users to place time markers for online data analysis.