New Hemodynamic Parameters in Peri-Operative and Critical Care-Challenges in Translation.

Hemodynamic monitoring technologies are evolving continuously-a large number of bedside monitoring options are becoming available in the clinic. Methods such as echocardiography, electrical bioimpedance, and calibrated/uncalibrated analysis of pulse contours are becoming increasingly common. This is leading to a decline in the use of highly invasive monitoring and allowing for safer, more accurate, and continuous measurements. The new devices mainly aim to monitor the well-known hemodynamic variables (e.g., novel pulse contour, bioreactance methods are aimed at measuring widely-used variables such as blood pressure, cardiac output). Even though hemodynamic monitoring is now safer and more accurate, a number of issues remain due to the limited amount of information available for diagnosis and treatment. Extensive work is being carried out in order to allow for more hemodynamic parameters to be measured in the clinic. In this review, we identify and discuss the main sensing strategies aimed at obtaining a more complete picture of the hemodynamic status of a patient, namely: (i) measurement of the circulatory system response to a defined stimulus; (ii) measurement of the microcirculation; (iii) technologies for assessing dynamic vascular mechanisms; and (iv) machine learning methods. By analyzing these four main research strategies, we aim to convey the key aspects, challenges, and clinical value of measuring novel hemodynamic parameters in critical care.

Minimally-invasive, real-time, non-destructive, species-independent phytohormone biosensor for precision farming.

To keep up with population growth, precision farming technologies must be implemented to sustainably increase agricultural output. The impact of such technologies can be expanded by monitoring phytohormones, such as salicylic acid. In this study, we present a plant-wearable electrochemical sensor for in situ detection of salicylic acid. The sensor utilizes microneedle-based electrodes that are functionalized with a layer of salicylic acid selective magnetic molecularly imprinted polymers. The sensor's capability to detect the phytohormone is demonstrated both in vitro and in vivo with a limit of detection of 2.74 µM and a range of detection that can reach as high as 150 µM. Furthermore, the selectivity of the sensor is verified by testing the sensor on commonly occurring phytohormones. Finally, we demonstrate the capability of the sensor to detect the onset of fungal infestation in Tobacco 5 min post-inoculation. This work shows that the sensor could serve as a promising platform for continuous and non-destructive monitoring in the field and as a fundamental research tool when coupled with a portable potentiostat.

Wearable Electrochemical Microneedle Sensor for Continuous Monitoring of Levodopa: Toward Parkinson Management.

Levodopa is the most effective medication for treating Parkinson's disease (PD). However, because dose optimization is currently based on patients' report of symptoms, which are difficult for patients to describe, the management of PD is challenging. We report on a microneedle sensing platform for continuous minimally invasive orthogonal electrochemical monitoring of levodopa (L-Dopa). The new multimodal microneedle sensing platform relies on parallel simultaneous independent enzymatic-amperometric and nonenzymatic voltammetric detection of L-Dopa using different microneedles on the same sensor array patch. Such real-time orthogonal L-Dopa sensing offers a built-in redundancy and enhances the information content of the microneedle sensor arrays. This is accomplished by rapid detection of L-Dopa using square-wave voltammetry and chronoamperometry at unmodified and tyrosinase-modified carbon-paste microneedle electrodes, respectively. The new wearable microneedle sensor device displays an attractive analytical performance with the enzymatic and nonenzymatic L-Dopa microneedle sensors offering different dimensions of information while displaying high sensitivity (with a low detection limit), high selectivity in the presence of potential interferences, and good stability in artificial interstitial fluid (ISF). The attractive analytical performance and potential wearable applications of the microneedle sensor array have been demonstrated in a skin-mimicking phantom gel as well as upon penetration through mice skin. The design and attractive analytical performance of the new orthogonal wearable microneedle sensor array hold considerable promise for reliable, continuous, minimally invasive monitoring of L-Dopa in the ISF toward optimizing the dosing regimen of the drug and effective management of Parkinson disease.

Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis.

Of the patients undergoing radical cystectomy, 20-80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes. Patients were prospectively recruited between 2013 and 2017. Patients with metastatic relapse had significantly higher ctDNA levels compared with disease-free patients (p<0.001). The median positive lead time between ctDNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions. PATIENT SUMMARY: Measurement of tumour-specific mutations in plasma and urine may be a powerful tool to monitor response during treatment and identify early signs of metastatic disease.

Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays.

The present work describes an attractive skin-worn microneedle sensing device for the minimally invasive electrochemical monitoring of subcutaneous alcohol. The device consists of an assembly of pyramidal microneedle structures integrated with Pt and Ag wires, each with a microcavity opening. The microneedle aperture was modified by electropolymerizing o-phenylene diamine onto the Pt wire microtransducer, followed by the immobilization of alcohol oxidase (AOx) in an intermediate chitosan layer, along with an outer Nafion layer. The resulting microneedle-based enzyme electrode displays an interference-free ethanol detection in artificial interstitial fluid without compromising its sensitivity, stability and response time. The skin penetration ability and the efficaciousness of the biosensor performance towards subcutaneous alcohol monitoring was substantiated by the ex vivo mice skin model analysis. Our results reveal that the new microneedle sensor holds considerable promise for continuous non-invasive alcohol monitoring in real-life situations.

Passive leg raising test with minimally invasive monitoring: the way forward for guiding septic shock resuscitation?

BACKGROUND: Swift and adequate fluid loading is a cornerstone of septic shock therapy. Yet, careful assessment of volume responsiveness and volume amount during the resuscitation process is a prerequisite. Both overzealous initial fluid administration and late fluid overload are harmful and may be associated with increased mortality. MAIN BODY: Static (i.e., central venous or pulmonary artery occlusion) pressure readings are erroneous for monitoring fluid resuscitation and should be abandoned. Dynamic measurements (i.e., stroke volume and pulse pressure variation) better predict fluid responsiveness than static filling pressures but the conditions necessary for these parameters to correctly evaluate preload dependency are frequently not met. The passive leg raising maneuver as a means to alter biventricular preload in combination with real-time measurement of cardiac output changes is an easy-to-use, fast, relatively unbiased, and accurate bedside test to guide fluid management and to avoid fluid overload during early septic shock treatment. Moreover, PLR may also be particularly useful to assist various treatments that trigger fluid removal during the "de-resuscitation" phase of septic shock. CONCLUSIONS: The passive leg raising maneuver in combination with real-time measurement of cardiac output changes is an easy-to-use, fast, relatively unbiased, and accurate bedside test to guide fluid management during septic shock.

Pulse waveform hemodynamic monitoring devices: recent advances and the place in goal-directed therapy in cardiac surgical patients.

Hemodynamic monitoring has evolved and improved greatly during the past decades as the medical approach has shifted from a static to a functional approach. The technological advances have led to innovating calibrated or not, but minimally invasive and noninvasive devices based on arterial pressure waveform (APW) analysis. This systematic clinical review outlines the physiologic rationale behind these recent technologies. We describe the strengths and the limitations of each method in terms of accuracy and precision of measuring the flow parameters (stroke volume, cardiac output) and dynamic parameters which predict the fluid responsiveness. We also analyzed the place of the APW monitoring devices in goal-directed therapy (GDT) protocols in cardiac surgical patients. According to the data from the three GDT-randomized control trials performed in cardiac surgery (using two types of APW techniques PiCCO and FloTrac/Vigileo), these devices did not demonstrate that they played a role in decreasing mortality, but only decreasing the ventilation time and the ICU and hospital length of stay.

Arterial waveform analysis.

The bedside measurement of continuous arterial pressure values from waveform analysis has been routinely available via indwelling arterial catheterization for >50 years. Invasive blood pressure monitoring has been utilized in critically ill patients, in both the operating room and critical care units, to facilitate rapid diagnoses of cardiovascular insufficiency and monitor response to treatments aimed at correcting abnormalities before the consequences of either hypo- or hypertension are seen. Minimally invasive techniques to estimate cardiac output (CO) have gained increased appeal. This has led to the increased interest in arterial waveform analysis to provide this important information, as it is measured continuously in many operating rooms and intensive care units. Arterial waveform analysis also allows for the calculation of many so-called derived parameters intrinsically created by this pulse pressure profile. These include estimates of left ventricular stroke volume (SV), CO, vascular resistance, and during positive-pressure breathing, SV variation, and pulse pressure variation. This article focuses on the principles of arterial waveform analysis and their determinants, components of the arterial system, and arterial pulse contour. It will also address the advantage of measuring real-time CO by the arterial waveform and the benefits to measuring SV variation. Arterial waveform analysis has gained a large interest in the overall assessment and management of the critically ill and those at a risk of hemodynamic deterioration.