Evaluating the Possibility of Translating Technological Advances in Non-Invasive Continuous Lactate Monitoring into Critical Care.

Lactate is widely measured in critically ill patients as a robust indicator of patient deterioration and response to treatment. Plasma concentrations represent a balance between lactate production and clearance. Analysis has typically been performed with the aim of detecting tissue hypoxia. However, there is a diverse range of processes unrelated to increased anaerobic metabolism that result in the accumulation of lactate, complicating clinical interpretation. Further, lactate levels can change rapidly over short spaces of time, and even subtle changes can reflect a profound change in the patient’s condition. Hence, there is a significant need for frequent lactate monitoring in critical care. Lactate monitoring is commonplace in sports performance monitoring, given the elevation of lactate during anaerobic exercise. The desire to continuously monitor lactate in athletes has led to the development of various technological approaches for non-invasive, continuous lactate measurements. This review aims firstly to reflect on the potential benefits of non-invasive continuous monitoring technology within the critical care setting. Secondly, we review the current devices used to measure lactate non-invasively outside of this setting and consider the challenges that must be overcome to allow for the translation of this technology into intensive care medicine. This review will be of interest to those developing continuous monitoring sensors, opening up a new field of research

Evaluating the Possibility of Translating Technological Advances in Non-Invasive Continuous Lactate Monitoring into Critical Care

Lactate is widely measured in critically ill patients as a robust indicator of patient deterioration and response to treatment. Plasma concentrations represent a balance between lactate production and clearance. Analysis has typically been performed with the aim of detecting tissue hypoxia. However, there is a diverse range of processes unrelated to increased anaerobic metabolism that result in the accumulation of lactate, complicating clinical interpretation. Further, lactate levels can change rapidly over short spaces of time, and even subtle changes can reflect a profound change in the patient’s condition. Hence, there is a significant need for frequent lactate monitoring in critical care. Lactate monitoring is commonplace in sports performance monitoring, given the elevation of lactate during anaerobic exercise. The desire to continuously monitor lactate in athletes has led to the development of various technological approaches for non-invasive, continuous lactate measurements. This review aims firstly to reflect on the potential benefits of non-invasive continuous monitoring technology within the critical care setting. Secondly, we review the current devices used to measure lactate non-invasively outside of this setting and consider the challenges that must be overcome to allow for the translation of this technology into intensive care medicine. This review will be of interest to those developing continuous monitoring sensors, opening up a new field of research

Molecularly imprinted polymer based electrochemical biosensors: Overcoming the challenges of detecting vital biomarkers and speeding up diagnosis

Electrochemical biosensors for the detection of vital biomarkers is a well-established technology that utilises a transducer and recognition element in tandem to determine the presence of an analyte. There is growing interest in using Molecularly Imprinted Polymers (MIPs) as recognition elements in a wide range of sensing devices due to their economic viability and scalability. The inherent properties of polymer platforms, alongside the vast array of monomeric options, synthetic routes and incorporation strategies allow for the production of a multitude of sensitive and selective recognition elements that have significant advantages over classically utilised biological entities. MIPs exhibit superior chemical and thermal stability offering a wider variety of immobilization/incorporation strategies, virtually unlimited ambient shelf-life and a longer product lifetime, whilst the vast array of monomers available offer flexibility to their synthesis. Even though some sensor platforms have been reported for the detection of vital biomarkers, the use of MIPs has a number of challenges and drawbacks that need to be overcome in order to produce sensing platforms with the required sensitivity and specificity for clinical use. In this review, we will provide an overview of the reasoning behind using MIPs as recognition elements in electrochemical biosensors for vital biomarkers, discuss the problems synergizing MIPs and electrochemical read-out strategies and offer insights into the future perspectives of this promising and innovative technology

Modular Synthesis and Biological Investigation of 5-Hydroxymethyl Dibenzyl Butyrolactones and Related Lignans

Dibenzyl butyrolactone lignans are well known for their excellent biological properties, particularly for their notable anti-proliferative activities. Herein we report a novel, efficient, convergent synthesis of dibenzyl butyrolactone lignans utilizing the acyl-Claisen rearrangement to stereoselectively prepare a key intermediate. The reported synthetic route enables the modification of these lignans to give rise to 5-hydroxymethyl derivatives of these lignans. The biological activities of these analogues were assessed, with derivatives showing an excellent cytotoxic profile which resulted in programmed cell death of Jurkat T-leukemia cells with less than 2% of the incubated cells entering a necrotic cell death pathway

Antimicrobial Strategies and Economic Considerations for Polymeric Medical Implants.

Healthcare acquired infections (HAI's) are a worldwide problem that can be exacerbated by surgery and the implantation of polymeric medical devices. The use of polymer based medical devices which incorporate antimicrobial strategies are now becoming an increasingly routine way of trying to prevent the potential for reduce chronic infection and device failure. There are a wide range of potential antimicrobial agents currently being incorporated into such polymers. However, it is difficult to determine which antimicrobial agent provides the greatest infection control. The economics of replacing current methods with impregnated polymer materials further complicates matters. It has been suggested that the use of a holistic system wide approach should to be developed around the implantation of medical devices which minimises the potential risk of infection. However, the use of such different approaches is still being developed. The control of such infections is important for individual patient health and the economic implications for healthcare services

Immature platelet indices alongside procalcitonin for sensitive and specific identification of bacteremia in the intensive care unit

Hematological markers that can be rapidly analyzed and regularly monitored during a patient’s stay on ICU, and that can identify bacterial causes of sepsis are being extensively sought. The significance of platelets in early immunological responses provides justification for assessing their usefulness in the identification of bacteremia amongst sepsis patients. In this preliminary study, the full blood count, including the platelet count by impedance (PLT-I), Immature Platelet Fraction (IPF%) and absolute immature platelet count (AIPC), were analyzed in eighty-two sepsis patients daily over the first 5 days stay on ICU. C-Reactive Protein (CRP), procalcitonin (PCT), and lactate were also analyzed daily. Blood cultures confirmed or excluded the presence of bacteremia. PCT provided the earliest indicator of bacteremia, with significant differences between the two cohorts on day 1. The change in IPF% and AIPC from day 1 to day 2 (Δ IPF% and Δ AIPC) provided the most accurate indication; A combination of Δ IPF% and day 2 PCT, provided a positive predictive value and negative predictive value of 100% and 96.10%, respectively. These data provide strong justification for larger multi-center validation studies to confirm the usefulness of these platelet indices during the assessment of sepsis on the ICU

Immature platelet fraction as a useful marker in the etiological determination of thrombocytopenia

© 2019 ISEH -- Society for Hematology and Stem Cells The etiology of thrombocytopenia is important in treatment and management of the condition. Most platelet parameters that are routinely analyzed in the diagnostic laboratory have not proven useful in identifying the etiology, while specialized assays suffer from poor standardization and lack of agreement between laboratories. The immature platelet fraction (IPF), which indirectly provides a measure of bone marrow function, is showing promise as a valuable marker of thrombopoietic responses. This study set out determine whether the IPF could effectively identify specific underlying etiologies of thrombocytopenia in a large thrombocytopenic cohort, to allow for quicker, more effective management of the condition. The IPF was analyzed in a large cohort of 637 thrombocytopenic patients and 171 healthy control patients on the Sysmex XN 10 hematology analyzer using the specialized fluorescence optical analysis. The thrombocytopenic patients were divided into six cohorts based on etiology. The IPF% was significantly higher in cases of increased platelet consumption (median = 9.55, min = 1.1, max = 77.9) or pseudothrombocytopenia (median = 13.1, min = 0.4, max = 28.8) compared with control (median = 4.2, min = 1.3, max = 12.8). Furthermore, the IPF% was also able to identify idiopathic thrombocytopenic purpura (ITP) (p < 0.05) (median = 13.4, min = 2.8, max = 77.9) from other causes of increased platelet consumptive disorders (infection: median = 6.4, min = 1.1, max = 21.6; hemorrhage: median = 8.9, min = 1.2, max = 20.2). By use of this large thrombocytopenic cohort, the IPF% has been found to be of significant diagnostic value, providing a useful rapid test in the etiological investigation of platelet disorders