Does it work in childhood and adolescence? The predictive role of postoperative/preablative stimulated thyroglobulin levels in paediatric thyroid cancer. A systematic review of the literature.

BACKGROUND: Thyroglobulin is a well-established disease marker during follow-up in paediatric differentiated thyroid cancer. However, no conclusive data on the role of endogenously stimulated thyroglobulin after thyroidectomy (ptTg) in predicting disease-specific outcomes are available. This review aims to establish the prognostic value of ptTg in children with DTC. METHODS: Online medical databases were searched for studies evaluating the association between ptTg and disease-specific outcomes in DTC-affected children. Documents not in English, preclinical studies, other review articles, case reports, and small case series were excluded. The risk of bias was assessed with the QUADAS-2 tool. RESULTS: Twelve studies, analysing 1043 children in total, were included in the review. They all had a retrospective design and were published between 2016 and 2022. Of all patients, 1008 (97%) and 849 (81%) had undergone thyroidectomy and RAI, respectively. Eight studies (756 children) evaluated the correlation between ptTg and disease persistence/relapse: six reported a significant association between these parameters; a specific ptTg cut-off (10-14 ng/ml) was identified at the multivariate analysis in three studies. The remaining four studies assessed the link between ptTg levels and disease extension, with three reporting a correlation between ptTg and lung/nodal metastases. DISCUSSION: ptTg is a readily available and inexpensive parameter, bearing a strong prognostic power in identifying disease persistence, relapse, and the presence of metastases in children affected by DTC.

High-Endurance Long-Term Potentiation in Neuromorphic Organic Electrochemical Transistors by PEDOT:PSS Electrochemical Polymerization on the Gate Electrode.

The brain exhibits extraordinary information processing capabilities thanks to neural networks that can operate in parallel with minimal energy consumption. Memory and learning require the creation of new neural networks through the long-term modification of the structure of the synapses, a phenomenon called long-term plasticity. Here, we use an organic electrochemical transistor to simulate long-term potentiation and depotentiation processes. Similarly to what happens in a synapse, the polymerization of the 3,4-ethylenedioxythiophene (EDOT) on the gate electrode modifies the structure of the device and boosts the ability of the gate potential to modify the conductivity of the channel. Operando AFM measurements were carried out to demonstrate the correlation between neuromorphic behavior and modification of the gate electrode. Long-term enhancement depends on both the number of pulses used and the gate potential, which generates long-term potentiation when a threshold of +0.7 V is overcome. Long-term depotentiation occurs by applying a +3.0 V potential and exploits the overoxidation of the deposited PEDOT:PSS. The induced states are stable for at least 2 months. The developed device shows very interesting characteristics in the field of neuromorphic electronics.

From Traditional to New Benchmark Catalysts for CO2 Electroreduction.

In the last century, conventional strategies pursued to reduce or convert CO2 have shown limitations and, consequently, have been pushing the development of innovative routes. Among them, great efforts have been made in the field of heterogeneous electrochemical CO2 conversion, which boasts the use of mild operative conditions, compatibility with renewable energy sources, and high versatility from an industrial point of view. Indeed, since the pioneering studies of Hori and co-workers, a wide range of electrocatalysts have been designed. Starting from the performances achieved using traditional bulk metal electrodes, advanced nanostructured and multi-phase materials are currently being studied with the main goal of overcoming the high overpotentials usually required for the obtainment of reduction products in substantial amounts. This review reports the most relevant examples of metal-based, nanostructured electrocatalysts proposed in the literature during the last 40 years. Moreover, the benchmark materials are identified and the most promising strategies towards the selective conversion to high-added-value chemicals with superior productivities are highlighted.

Focus Review on Nanomaterial-Based Electrochemical Sensing of Glucose for Health Applications.

Diabetes management can be considered the first paradigm of modern personalized medicine. An overview of the most relevant advancements in glucose sensing achieved in the last 5 years is presented. In particular, devices exploiting both consolidated and innovative electrochemical sensing strategies, based on nanomaterials, have been described, taking into account their performances, advantages and limitations, when applied for the glucose analysis in blood and serum samples, urine, as well as in less conventional biological fluids. The routine measurement is still largely based on the finger-pricking method, which is usually considered unpleasant. In alternative, glucose continuous monitoring relies on electrochemical sensing in the interstitial fluid, using implanted electrodes. Due to the invasive nature of such devices, further investigations have been carried out in order to develop less invasive sensors that can operate in sweat, tears or wound exudates. Thanks to their unique features, nanomaterials have been successfully applied for the development of both enzymatic and non-enzymatic glucose sensors, which are compliant with the specific needs of the most advanced applications, such as flexible and deformable systems capable of conforming to skin or eyes, in order to produce reliable medical devices operating at the point of care.

Smart Bandaid Integrated with Fully Textile OECT for Uric Acid Real-Time Monitoring in Wound Exudate.

Hard-to-heal wounds (i.e., severe and/or chronic) are typically associated with particular pathologies or afflictions such as diabetes, immunodeficiencies, compression traumas in bedridden people, skin grafts, or third-degree burns. In this situation, it is critical to constantly monitor the healing stages and the overall wound conditions to allow for better-targeted therapies and faster patient recovery. At the moment, this operation is performed by removing the bandages and visually inspecting the wound, putting the patient at risk of infection and disturbing the healing stages. Recently, new devices have been developed to address these issues by monitoring important biomarkers related to the wound health status, such as pH, moisture, etc. In this contribution, we present a novel textile chemical sensor exploiting an organic electrochemical transistor (OECT) configuration based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) for uric acid (UA)-selective monitoring in wound exudate. The combination of special medical-grade textile materials provides a passive sampling system that enables the real-time and non-invasive analysis of wound fluid: UA was detected as a benchmark analyte to monitor the health status of wounds since it represents a relevant biomarker associated with infections or necrotization processes in human tissues. The sensors proved to reliably and reversibly detect UA concentration in synthetic wound exudate in the biologically relevant range of 220-750 µM, operating in flow conditions for better mimicking the real wound bed. This forerunner device paves the way for smart bandages integrated with real-time monitoring OECT-based sensors for wound-healing evaluation.

Micro- and nano-devices for electrochemical sensing.

Electrode miniaturization has profoundly revolutionized the field of electrochemical sensing, opening up unprecedented opportunities for probing biological events with a high spatial and temporal resolution, integrating electrochemical systems with microfluidics, and designing arrays for multiplexed sensing. Several technological issues posed by the desire for downsizing have been addressed so far, leading to micrometric and nanometric sensing systems with different degrees of maturity. However, there is still an endless margin for researchers to improve current strategies and cope with demanding sensing fields, such as lab-on-a-chip devices and multi-array sensors, brain chemistry, and cell monitoring. In this review, we present current trends in the design of micro-/nano-electrochemical sensors and cutting-edge applications reported in the last 10 years. Micro- and nanosensors are divided into four categories depending on the transduction mechanism, e.g., amperometric, impedimetric, potentiometric, and transistor-based, to best guide the reader through the different detection strategies and highlight major advancements as well as still unaddressed demands in electrochemical sensing.

Oxygen Gas Sensing Using a Hydrogel-Based Organic Electrochemical Transistor for Work Safety Applications.

Oxygen depletion in confined spaces represents one of the most serious and underestimated dangers for workers. Despite the existence of several commercially available and widely used gas oxygen sensors, injuries and deaths from reduced oxygen levels are still more common than for other hazardous gases. Here, we present hydrogel-based organic electrochemical transistors (OECTs) made with the conducting polymer poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) as wearable and real-time oxygen gas sensors. After comparing OECT performances using liquid and hydrogel electrolytes, we identified the best PEDOT:PSS active layer and hydrogel coating (30 µm) combination for sensing oxygen in the concentration range of 13−21% (v/v), critical for work safety applications. The fast O2 solubilization in the hydrogel allowed for gaseous oxygen transduction in an electrical signal thanks to the electrocatalytic activity of PEDOT:PSS, while OECT architecture amplified the response (gain ~ 104). OECTs proved to have comparable sensitivities if fabricated on glass and thin plastic substrates, (−12.2 ± 0.6) and (−15.4 ± 0.4) µA/dec, respectively, with low power consumption (<40 µW). Sample bending does not influence the device response, demonstrating that our real-time conformable and lightweight sensor could be implemented as a wearable, noninvasive safety tool for operators working in potentially hazardous confined spaces.

A Wearable Electrochemical Gas Sensor for Ammonia Detection.

The next future strategies for improved occupational safety and health management could largely benefit from wearable and Internet of Things technologies, enabling the real-time monitoring of health-related and environmental information to the wearer, to emergency responders, and to inspectors. The aim of this study is the development of a wearable gas sensor for the detection of NH3 at room temperature based on the organic semiconductor poly(3,4-ethylenedioxythiophene) (PEDOT), electrochemically deposited iridium oxide particles, and a hydrogel film. The hydrogel composition was finely optimised to obtain self-healing properties, as well as the desired porosity, adhesion to the substrate, and stability in humidity variations. Its chemical structure and morphology were characterised by infrared spectroscopy and scanning electron microscopy, respectively, and were found to play a key role in the transduction process and in the achievement of a reversible and selective response. The sensing properties rely on a potentiometric-like mechanism that significantly differs from most of the state-of-the-art NH3 gas sensors and provides superior robustness to the final device. Thanks to the reliability of the analytical response, the simple two-terminal configuration and the low power consumption, the PEDOT:PSS/IrOx Ps/hydrogel sensor was realised on a flexible plastic foil and successfully tested in a wearable configuration with wireless connectivity to a smartphone. The wearable sensor showed stability to mechanical deformations and good analytical performances, with a sensitivity of 60 ± 8 µA decade-1 in a wide concentration range (17-7899 ppm), which includes the safety limits set by law for NH3 exposure.

Nanostructured Copper-Based Electrodes Electrochemically Synthesized on a Carbonaceous Gas Diffusion Membrane with Catalytic Activity for the Electroreduction of CO2.

In this work, four different 4 cm2-sized nanostructured Cu-based electrocatalysts have been designed by a one-step electrodeposition process of Cu metal on a three-dimensional carbonaceous membrane. One consisted of Cu0, and the other three were obtained by further simple oxidative treatments. Morphological, structural, and electrochemical investigations on the four materials were carried out by scanning electron microscopy, Raman spectroscopy, X-ray diffraction, linear sweep voltammetry, and potential-controlled electrolysis. All the electrocatalysts showed promising catalytic activities toward CO2 electroreduction in liquid phase, with a remarkable selectivity toward acetic acid achieved when using the oxidized materials. In particular, the best electrocatalytic activity was observed for the Cu2O-Cu0 catalyst, working at a relatively low potential (-0.4 V vs RHE), which exhibited a stable and low current density of 0.46 mA cm-2 and a productivity of 308 µmol gcat-1 h-1. These results were attributed to the nanostructured morphology that is characterized by many void spaces and by a high surface area, which should guarantee a large number of CuI and Cu0 catalytic active sites. Moreover, kinetic analyses and preliminary studies about catalyst regeneration highlighted the stability of the best-performing catalyst.

Advanced Wound Dressing for Real-Time pH Monitoring.

The rapid evolution of wearable technologies is giving rise to a strong push for textile chemical sensors design targeting the real-time collection of vital parameters for improved healthcare. Among the most promising applications, monitoring of nonhealing wounds is a scarcely explored medical field that still lacks quantitative tools for the management of the healing process. In this work, a smart bandage is developed for the real-time monitoring of wound pH, which has been reported to correlate with the healing stages, thus potentially giving direct access to the wound status without disturbing the wound bed. The fully textile device is realized by integrating a sensing layer, including the two-terminal pH sensor made of a semiconducting polymer and iridium oxide particles, and an absorbent layer ensuring the delivery of a continuous wound exudate flow across the sensor area. The two-terminal sensor exhibits a reversible response with a sensitivity of (59 ± 4) µA pH-1 in the medically relevant pH range for wound monitoring (pH 6-9), and its performance is not substantially affected either by the presence of the most common chemical interferents or by temperature gradients from 22 to 40 °C. Thanks to the robust sensing mechanism based on potentiometric transduction and the simple device geometry, the fully assembled smart bandage was successfully validated in flow analysis using synthetic wound exudate.

Textile Chemical Sensors Based on Conductive Polymers for the Analysis of Sweat.

Wearable textile chemical sensors are promising devices due to the potential applications in medicine, sports activities and occupational safety and health. Reaching the maturity required for commercialization is a technology challenge that mainly involves material science because these sensors should be adapted to flexible and light-weight substrates to preserve the comfort of the wearer. Conductive polymers (CPs) are a fascinating solution to meet this demand, as they exhibit the mechanical properties of polymers, with an electrical conductivity typical of semiconductors. Moreover, their biocompatibility makes them promising candidates for effectively interfacing the human body. In particular, sweat analysis is very attractive to wearable technologies as perspiration is a naturally occurring process and sweat can be sampled non-invasively and continuously over time. This review discusses the role of CPs in the development of textile electrochemical sensors specifically designed for real-time sweat monitoring and the main challenges related to this topic.

Stranger Months: How SARS-CoV-2, Fear of Contagion, and Lockdown Measures Impacted Attendance and Clinical Activity During February and March 2020 at an Urban Emergency Department in Milan.

OBJECTIVES: An unprecedented wave of patients with acute respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) hit emergency departments (EDs) in Lombardy, starting in the second half of February 2020. This study describes the direct and indirect impacts of the SARS-CoV-2 outbreak on an urban major-hospital ED. METHODS: Data regarding all patients diagnosed with COVID-19 presenting from February 1 to March 31, 2020, were prospectively collected, while data regarding non-COVID patients presenting within the same period in 2019 were retrospectively retrieved. RESULTS: ED attendance dropped by 37% in 2020. Two-thirds of this reduction occurred early after the identification of the first autochthonous COVID-19 case in Lombardy, before lockdown measures were enforced. Hospital admissions of non-COVID patients fell by 26%. During the peak of COVID-19 attendance, the ED faced an extraordinary increase in: patients needing oxygen (+239%) or noninvasive ventilation (+725%), transfers to the intensive care unit (+57%), and in-hospital mortality (+309%), compared with the same period in 2019. CONCLUSIONS: The COVID-19 outbreak determined an unprecedented upsurge in respiratory failure cases and mortality. Fear of contagion triggered a spontaneous, marked reduction of ED attendance, and, presumably, some as yet unknown quantity of missed or delayed diagnoses for conditions other than COVID-19.

Textile sensors platform for the selective and simultaneous detection of chloride ion and pH in sweat.

The development of wearable sensors, in particular fully-textile ones, is one of the most interesting open challenges in bioelectronics. Several and significant steps forward have been taken in the last decade in order to achieve a compact, lightweight, cost-effective, and easy to wear platform for healthcare and sport activities real-time monitoring. We have developed a fully textile, multi-thread biosensing platform that can detect different bioanalytes simultaneously without interference, and, as an example, we propose it for testing chloride ions (Cl-) concentration and pH level. The textile sensors are simple threads, based on natural and synthetic fibers, coated with the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene-sulfonate) (PEDOT:PSS) and properly functionalized with either a nano-composite material or a chemical sensitive dye to obtain Cl- and pH selective sensing functionality, respectively. The single-thread sensors show excellent sensitivity, reproducibility, selectivity, long term stability and the ability to work with small volumes of solution. The performance of the developed textile devices is demonstrated both in buffer solution and in artificial human perspiration to perform on-demand and point-of-care epidermal fluids analysis. The possibility to easily knit or sew the thread sensors into fabrics opens up a new vision for a textile wearable multi-sensing platform achievable in the near future.

Needle-type organic electrochemical transistor for spatially resolved detection of dopamine.

In this work, the advantages of carbon nanoelectrodes (CNEs) and orgonic electrochemical transistors (OECTs) were merged to realise nanometre-sized, spearhead OECTs based on single- and double-barrel CNEs functionalised with a conducting polymer film. The needle-type OECT shows a high aspect ratio that allows its precise positioning by means of a macroscopic handle and its size is compatible with single-cell analysis. The device was characterised with respect to its electrolyte-gated behaviour and was employed as electrochemical sensor for the proof-of-concept detection of dopamine (DA) over a wide concentration range (10-12-10-6 M). Upon application of fixed drain and gate voltages (Vd = - 0.3 V, Vg = - 0.9 V, respectively), the nano-sized needle-type OECT sensor exhibited a linear response in the low pM range and from 0.002 to 7 µM DA, with a detection limit of 1 × 10-12 M. Graphical abstract.

Layered Double Hydroxide-Modified Organic Electrochemical Transistor for Glucose and Lactate Biosensing.

Biosensors based on Organic Electrochemical Transistors (OECTs) are developed for the selective detection of glucose and lactate. The transistor architecture provides signal amplification (gain) with respect to the simple amperometric response. The biosensors are based on a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel and the gate electrode is functionalised with glucose oxidase (GOx) or lactate oxidase (LOx) enzymes, which are immobilised within a Ni/Al Layered Double Hydroxide (LDH) through a one-step electrodeposition procedure. The here-designed OECT architecture allows minimising the required amount of enzyme during electrodeposition. The output signal of the biosensor is the drain current (Id), which decreases as the analyte concentration increases. In the optimised conditions, the biosensor responds to glucose in the range of 0.1-8.0 mM with a limit of detection (LOD) of 0.02 mM. Two regimes of proportionality are observed. For concentrations lower than 1.0 mM, a linear response is obtained with a mean gain of 360, whereas for concentrations higher than 1.0 mM, Id is proportional to the logarithm of glucose concentration, with a gain of 220. For lactate detection, the biosensor response is linear in the whole concentration range (0.05-8.0 mM). A LOD of 0.04 mM is reached, with a net gain equal to 400.

Organic Electrochemical Transistors as Versatile Analytical Potentiometric Sensors.

Potentiometric transduction is an important tool of analytical chemistry to record chemical signals, but some constraints in the miniaturization and low-cost fabrication of the reference electrode are a bottleneck in the realization of more-advanced devices such as wearable and lab-on-a-chip sensors. Here, an organic electrochemical transistor (OECT) has been designed with an alternative architecture that allows to record the potentiometric signals of gate electrodes, which have been chemically modified to obtain Ag/AgnX interfaces (X = Cl-, Br-, I-, and S2-), without the use of a reference electrode. When the OECT is immersed in a sample solution, it reaches an equilibrium state, because PEDOT:PSS exchanges charges with the electrolyte until its Fermi level is aligned to the one of Ag/AgnX. The latter is controlled by Xn- concentration in the solution. As a consequence, in this spontaneous process, the conductivity of PEDOT:PSS changes with the electrochemical potential of the modified gate electrode without any external bias. The sensor works by applying only a fixed drain current or drain voltage and thus the OECT sensor operates with just two terminals. It is also demonstrated that, in this configuration, gate potential values extracted from the drain current are in good agreement with the ones measured with respect to a reference electrode being perfectly correlated (linear slope equal to 1.00 ± 0.03). In the case of the sulfide anion, the OECT performance overcomes the limit represented by the Nernst equation, with a sensitivity of 0.52 V decade-1. The presented results suggest that OECTs could be a viable option to fabricate advanced sensors based on potentiometric transduction.

Microscopic Determination of Carrier Density and Mobility in Working Organic Electrochemical Transistors.

A comprehensive understanding of electrochemical and physical phenomena originating the response of electrolyte-gated transistors is crucial for improved handling and design of these devices. However, the lack of suitable tools for direct investigation of microscale effects has hindered the possibility to bridge the gap between experiments and theoretical models. In this contribution, a scanning probe setup is used to explore the operation mechanisms of organic electrochemical transistors by probing the local electrochemical potential of the organic film composing the device channel. Moreover, an interpretative model is developed in order to highlight the meaning of electrochemical doping and to show how the experimental data can give direct access to fundamental device parameters, such as local charge carrier concentration and mobility. This approach is versatile and provides insight into the organic semiconductor/electrolyte interface and useful information for materials characterization, device scaling, and sensing optimization.

PEDOT: Dye-Based, Flexible Organic Electrochemical Transistor for Highly Sensitive pH Monitoring.

Organic electrochemical transistors (OECTs) are bioelectronic devices able to bridge electronic and biological domains with especially high amplification and configurational versatility and thus stand out as promising platforms for healthcare applications and portable sensing technologies. Here, we have optimized the synthesis of two pH-sensitive composites of PEDOT (poly(3,4-ethylenedioxythiophene)) doped with pH dyes (BTB and MO, i.e., Bromothymol Blue and Methyl Orange, respectively), showing their ability to successfully convert the pH into an electrical signal. The PEDOT:BTB composite, which exhibited the best performance, was used as the gate electrode to develop an OECT sensor for pH monitoring that can reliably operate in a two-fold transduction mode with super-Nernstian sensitivity. When the OECT transconductance is employed as analytical signal, a sensitivity of 93 ± 8 mV pH unit-1 is achieved by successive sampling in aqueous electrolytes. When the detection is carried out by dynamically changing the pH of the same medium, the offset gate voltage of the OECT shifts by (1.1 ± 0.3) × 102 mV pH unit-1. As a further step, the optimized configuration was realized on a PET substrate, and the performance of the resulting flexible OECT was assessed in artificial sweat within a medically relevant pH range.

Selective detection of dopamine with an all PEDOT:PSS Organic Electrochemical Transistor.

An all PEDOT:PSS Organic Electrochemical Transistor (OECT) has been developed and used for the selective detection of dopamine (DA) in the presence of interfering compounds (ascorbic acid, AA and uric acid, UA). The selective response has been implemented using a potentiodynamic approach, by varying the operating gate voltage and the scan rate. The trans-conductance curves allow to obtain a linear calibration plot for AA, UA and DA and to separate the redox waves associated to each compound; for this purpose, the scan rate is an important parameter to achieve a good resolution. The sensitivities and limits of detection obtained with the OECT have been compared with those obtained by potential step amperometric techniques (cyclic voltammetry and differential pulse voltammetry), employing a PEDOT:PSS working electrode: our results prove that the all-PEDOT:PSS OECT sensitivities and limits of detection are comparable or even better than those obtained by DPV, a technique that employs a sophisticate potential wave and read-out system in order to maximize the performance of electrochemical sensors and that can hardly be considered a viable readout method in practical applications.

Imaging of early postoperative complications after polypropylene mesh repair of inguinal hernia.

PURPOSE: We report our experience with the use of US and CT in postoperative complications of inguinal hernioplasty using a prosthetic polypropylene mesh. MATERIALS AND METHODS: This study was divided into two parts. In the first we evaluated the in-vitro sonographic and CT appearance of a fragment of prosthetic mesh. In the second, we retrospectively reviewed the imaging findings in 31 patients (aged 42 to 75 years) examined after inguinal hernia repair between December 2000 and December 2002. Seventeen hernias had been repaired with a laparoscopic approach, and the others with the anterior tension-free technique proposed by Lichtenstein (12 cases) and Trabucco (2 cases). Sonography was performed to assess suspected complications between the second and the fourth postoperative day. Both high-resolution 7.5-10 MHz linear transducers and a 3.5 MHz convex probe were employed to ensure complete evaluation of superficial and deep structures. Eight obese patients also underwent CT for confirmation of the US results. RESULTS: At sonography the prosthetic mesh appeared as a linear hyperechoic image measuring about 2 mm in thickness, with posterior acoustic shadow and a finely irregular surface. Only one of the 17 patients examined after laparoscopic inguinal hernioplasty had a seroma; in the other 14 repaired with the anterior tension-free technique we identified 2 abscesses, 3 seromas, 2 "foldings" of the prosthetic mesh, and 2 mesh displacements with associated recurrence of hernia. CT confirmed the US results as to the presence of fluid collections, and visualised the prosthetic mesh in only 2/8 cases. CONCLUSIONS: Sonography is a useful means of assessing postoperative changes in laparoscopic and in anterior tension-free hernia repair. It can differentiate these complications from recurrences of hernia. Colour-Doppler US can also correctly detect normal blood flow of the testes. Sonography is the only technique that can easily demonstrate the prosthetic mesh in the abdominal wall.