Microdialysis in Abdominal Organ Transplantation and the Potential for Integration with Dynamic Preservation Platforms and Post Transplant Monitoring.

The perpetual organ shortage crisis worldwide has meant a paradigm shift in global thinking with subsequent expansion of the accepted criteria for an organ donor to meet the demand. Robust pre-transplant organ viability assessment is the next great challenge in the field of transplantation today. Organ preservation in the nature of static cold storage has reached its limits, and machine perfusion both cold and warm offers theoretically superior preservation and the potential to assess organs.

Cost-effectiveness of specialist eating disorders services for children and adolescents with anorexia nervosa: a national surveillance study.

Background: Evidence suggests specialist eating disorders services for children and adolescents with anorexia nervosa have the potential to improve outcomes and reduce costs through reduced hospital admissions. This study aimed to evaluate the cost-effectiveness of assessment and diagnosis in community-based specialist child and adolescent mental health services (CAMHS) compared to generic CAMHS for children and adolescents with anorexia nervosa.

Method: Observational, surveillance study of children and adolescents aged 8 to 17, in contact with community-based CAMHS in the UK or Republic of Ireland for a first episode of anorexia nervosa.

Fiber-Based Electrochemical Biosensors for Monitoring pH and Transient Neurometabolic Lactate.

Developing tools that are able to monitor transient neurochemical dynamics is important to decipher brain chemistry and function. Multifunctional polymer-based fibers have been recently applied to monitor and modulate neural activity. Here, we explore the potential of polymer fibers comprising six graphite-doped electrodes and two microfluidic channels within a flexible polycarbonate body as a platform for sensing pH and neurometabolic lactate.

Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers.

Background: Enhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based β-lactam biosensor in healthy volunteers.

Methods: This first-in-human, proof-of-concept study was done at the National Institute of Health Research/Wellcome Trust Imperial Clinical Research Facility (Imperial College London, London, UK).

Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application.

Background: Traumatic Brain Injury (TBI) is a leading cause of fatality and disability worldwide, partly due to the occurrence of secondary injury and late interventions. Correct diagnosis and timely monitoring ensure effective medical intervention aimed at improving clinical outcome. However, due to the limitations in size and cost of current ambulatory bioinstruments, they cannot be used to monitor patients who may still be at risk of secondary injury outside the ICU.

Complementary Metal-Oxide-Semiconductor Potentiometric Field-Effect Transistor Array Platform Using Sensor Learning for Multi-ion Imaging.

This work describes an array of 1024 ion-sensitive field-effect transistors (ISFETs) using sensor-learning techniques to perform multi-ion imaging for concurrent detection of potassium, sodium, calcium, and hydrogen. Analyte-specific ionophore membranes are deposited on the surface of the ISFET array chip, yielding pixels with quasi-Nernstian sensitivity to K, Na, or Ca. Uncoated pixels display pH sensitivity from the standard SiN passivation layer.

Real-time neurochemical measurement of dynamic metabolic events during cardiac arrest and resuscitation in a porcine model.

This work describes a fully-integrated portable microfluidic analysis system for real-time monitoring of dynamic changes in glucose and lactate occurring in the brain as a result of cardiac arrest and resuscitation. Brain metabolites are sampled using FDA-approved microdialysis probes and coupled to a high-temporal resolution 3D printed microfluidic chip housing glucose and lactate biosensors. The microfluidic biosensors are integrated with a wireless 2-channel potentiostat forming a compact analysis system that is ideal for use in a crowded operating theatre.

Portable Microfluidic Biosensing System for Real-Time Analysis of Microdialysate in Transplant Kidneys.

Currently, there is a severe shortage of donor kidneys that are fit for transplantation, due in part to a lack of adequate viability assessment tools for transplant organs. This work presents the integration of a novel wireless two-channel amperometric potentiostat with microneedle-based glucose and lactate biosensors housed in a 3D printed chip to create a microfluidic biosensing system that is genuinely portable. The wireless potentiostat transmits data via Bluetooth to an Android app running on a tablet.

Incidence of anorexia nervosa in young people in the UK and Ireland: a national surveillance study.

Objectives: This study aimed to estimate the incidence of DSM5 anorexia nervosa in young people in contact with child and adolescent mental health services in the UK and Ireland.

Design: Observational, surveillance study, using the Child and Adolescent Psychiatry Surveillance System, involving monthly reporting by child and adolescent psychiatrists between 1st February 2015 and 30th September 2015.

Setting: The study was based in the UK and Ireland.

An improved rapid sampling microdialysis system for human and porcine organ monitoring in a hospital setting.

Online organ monitoring could provide clinicians with critical information regarding organ health prior to transplantation and could aid clinical decision-making. This paper presents the methodology of online microdialysis for real-time monitoring of human organs . We describe how rapid sampling microdialysis can be incorporated with organ perfusion machines to create a robust organ monitoring system and demonstrate its use in monitoring human and porcine kidneys as well as human and porcine pancreases.

Clinical translation of microfluidic sensor devices: focus on calibration and analytical robustness.

We present approaches to facilitate the use of microfluidics outside of the laboratory, in our case within a clinical setting and monitoring from human subjects, where the complexity of microfluidic devices requires high skill and expertise and would otherwise limit translation. Microfluidic devices show great potential for converting complex laboratory protocols into on-chip processes. We demonstrate a flexible microfluidic platform can be coupled to microfluidic biosensors and used in conjunction with clinical microdialysis.

3D printed microfluidic device for online detection of neurochemical changes with high temporal resolution in human brain microdialysate.

This paper presents the design, optimisation and fabrication of a mechanically robust 3D printed microfluidic device for the high time resolution online analysis of biomarkers in a microdialysate stream at microlitre per minute flow rates. The device consists of a microfluidic channel with secure low volume connections that easily integrates electrochemical biosensors for biomarkers such as glutamate, glucose and lactate. The optimisation process of the microfluidic channel fabrication, including for different types of 3D printer, is explained and the resulting improvement in sensor response time is quantified.

Development of a Minimally Invasive Microneedle-Based Sensor for Continuous Monitoring of β-Lactam Antibiotic Concentrations in Vivo.

Antimicrobial resistance poses a global threat to patient health. Improving the use and effectiveness of antimicrobials is critical in addressing this issue. This includes optimizing the dose of antibiotic delivered to each individual.

Clinical value of bioelectrical properties of cancerous tissue in advanced epithelial ovarian cancer patients.

Currently, there are no valid pre-operatively established biomarkers or algorithms that can accurately predict surgical and clinical outcome for patients with advanced epithelial ovarian cancer (EOC). In this study, we suggest that profiling of tumour parameters such as bioelectrical-potential and metabolites, detectable by electronic sensors, could facilitate the future development of devices to better monitor disease and predict surgical and treatment outcomes. Biopotential was recorded, using a potentiometric measurement system, in ex vivo paired non-cancerous and cancerous omental tissues from advanced stage EOC (n = 36), and lysates collected for metabolite measurement by microdialysis.

Public acceptability of computer-controlled antibiotic management: An exploration of automated dosing and opportunities for implementation.

A paucity of data describing citizen perceptions of novel technologies, including those containing unsupervised computer-controlled systems is currently available. We explored citizen perceptions of using a microneedle biosensor and automated dose control system at a university public festival. Groups of citizens (from 2-6 people per group) attended a short demonstration of a microneedle biosensor and automated dosing system versus a traditional phlebotomy approach over a two-day public festival.

High temporal resolution delayed analysis of clinical microdialysate streams.

This paper presents the use of tubing to store clinical microdialysis samples for delayed analysis with high temporal resolution, offering an alternative to traditional discrete offline microdialysis sampling. Samples stored in this way were found to be stable for up to 72 days at -80 °C. Examples of how this methodology can be applied to glucose and lactate measurement in a wide range of in vivo monitoring experiments are presented.

An examination of the clinical outcomes of adolescents and young adults with broad autism spectrum traits and autism spectrum disorder and anorexia nervosa: A multi centre study.

Objectives: To compare the clinical outcomes of adolescents and young adults with anorexia nervosa (AN) comorbid with broad autism spectrum disorder (ASD) or ASD traits.

Method: The developmental and well-being assessment and social aptitude scale were used to categorize adolescents and young adults with AN (N = 149) into those with ASD traits (N = 23), and those who also fulfilled diagnostic criteria for a possible/probable ASD (N = 6). We compared both eating disorders specific measures and broader outcome measures at intake and 12 months follow-up.

Development of pancreatic machine perfusion: translational steps from porcine to human models.

Background: Hypothermic machine perfusion (HMP) is increasingly being used for extended criteria kidney grafts. Pancreatic HMP is challenging because physiologically the pancreas is a low-flow organ susceptible to edema. We report the successful development of preclinical HMP models using porcine pancreases, as well as human pancreases unsuitable for clinical transplantation.

A Pilot, Multicentre Pragmatic Randomised Trial to Explore the Impact of Carer Skills Training on Carer and Patient Behaviours: Testing the Cognitive Interpersonal Model in Adolescent Anorexia Nervosa.

Aim: The aim of the study is to establish the acceptability, feasibility and approximate size of the effect of adding a carer intervention [Experienced Caregivers Helping Others (ECHO)] to treatment as usual (TAU) for adolescents with anorexia nervosa.

Methods: The study is a pilot randomised trial comparing TAU (n = 50) alone or TAU plus ECHO with (n = 50) or without (n = 49) telephone guidance. Effect sizes (ESs) were regression coefficients standardised by baseline standard deviations of measure.

Review article: Novel technologies in the treatment and monitoring of advanced and relapsed epithelial ovarian cancer.

Epithelial Ovarian cancer (EOC) is the fifth most common cause of cancer death in females in the UK. It has long been recognized to be a set of heterogeneous diseases, with high grade serous being the most common subtype. The majority of patients with EOC present at an advanced stage (FIGO III-IV), and have the largest risk for disease recurrence from which a high percentage will develop resistance to chemotherapy.

An ex vivo comparison of adenosine and lidocaine solution and University of Wisconsin solution for hypothermic machine perfusion of porcine kidneys: potential for development.

Background: The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca, 16 mM Mg, and 4% albumin on kidney preservation compared with University Wisconsin solution (UW).

Organ Pretreatment With Cytotopic Endothelial Localizing Peptides to Ameliorate Microvascular Thrombosis and Perfusion Deficits in Ex Vivo Renal Hemoreperfusion Models.

Background: Hypothermic machine organ perfusion (HMP) offers opportunity to manipulate grafts with pharmacological agents prior to transplantation. Pretreating organs with novel cytotopic anticoagulant peptides that localize to endothelial cell membranes could ameliorate microvascular thrombotic sequelae posttransplantation. We describe experiments testing thrombalexin (TLN), a novel cell binding thrombin inhibitor, using porcine and unused human kidneys in a series of ex vivo normothermic hemoreperfusion models.

Simultaneous monitoring of potassium, glucose and lactate during spreading depolarization in the injured human brain - Proof of principle of a novel real-time neurochemical analysis system, continuous online microdialysis.

Spreading depolarizations occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an spreading depolarization requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential.