Respiratory challenges and ventilatory management in different types of acute brain-injured patients.

Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.

The mechanical power in neurocritical care patients: is it useful?

Patients with acute brain injury have been excluded in the majority of the randomized clinical trials which evaluated a lung protective strategy in patients with acute respiratory failure. It remains unclear if low tidal volume, higher PEEP levels and recruitment maneuvers by increasing both the intracranial and intrathoracic pressure and by leading to a permissible hypercapnia could furthermore deteriorate the acute brain injury and the final outcome. Mechanical power has been associated with the outcome in ARDS patients without brain injury. Jiang et al. demonstrated in neurocritical patients that non-survivors had a higher mechanical power compared to survivors. Mechanical power was associated with an increase in intensive care mortality risk and also to an enhanced risk of hospital mortality, prolonged intensive care length of stay and fewer ventilatory free days; in addition, the mechanical power could better predict mortality compared to the Glasgow Coma Scale.

Respiratory and peripheral muscular ultrasound characteristics in ICU COVID 19 ARDS patients.

PURPOSE: Severe cases of coronavirus disease 2019 develop ARDS requiring admission to the ICU. This study aimed to investigate the ultrasound characteristics of respiratory and peripheral muscles of patients affected by COVID19 who require mechanical ventilation. MATERIALS AND METHODS: This is a prospective observational study. We performed muscle ultrasound at the admission of ICU in 32 intubated patients with ARDS COVID19. The ultrasound was comprehensive of thickness and echogenicity of both parasternal intercostal and diaphragm muscles, and cross-sectional area and echogenicity of the rectus femoris. RESULTS: Patients who survived showed a significantly lower echogenicity score as compared with those who did not survive for both parasternal intercostal muscles. Similarly, the diaphragmatic echogenicity was significantly different between alive or dead patients. There was a significant correlation between right parasternal intercostal or diaphragm echogenicity and the cumulative fluid balance and urine protein output. Similar results were detected for rectus femoris echogenicity. CONCLUSIONS: The early changes detected by echogenicity ultrasound suggest a potential benefit of proactive early therapies designed to preserve respiratory and peripheral muscle architecture to reduce days on MV, although what constitutes a clinically significant change in muscle echogenicity remains unknown.

A validation study of a continuous automatic measurement of the mechanical power in ARDS patients.

The mechanical power (MP) is the energy delivered into the respiratory system over time. It can be computed as a direct measurement of the inspiratory area of the airway pressure and volume loop during the respiratory cycle or calculated by "power equations". The absence of a bedside computation limited its widespread use. Recently, it has been developed an automatic monitoring system inside of a mechanical ventilator. PURPOSE: Our aim was to investigate the repeatability and the accuracy of the measured MP at different PEEP values and tidal volume compared with the calculated MP. MATERIAL AND METHODS: MP was measured and calculated in sedated and paralyzed ARDS patients at low and high tidal volume, at 5-10-15 cmH2O of PEEP both in volume and pressure-controlled ventilation. The same measurements were performed twice. RESULTS: Fifty ARDS patients were enrolled. MP was measured and calculated for a total of 300 measurements. The bias and limits of agreement were 0.38 from -1.31 to 2.0 J/min. The measured and calculated MP were similar in each ventilatory condition. CONCLUSIONS: The mechanical power measured by a new automatic real time system implemented in a mechanical ventilator was repeatable and accurate compared with the computed one.

Applying deep neural networks and inertial measurement unit in recognizing irregular walking differences in the real world.

Falling injuries pose serious health risks to people of all ages, and knowing the extent of exposure to irregular surfaces will increase the ability to measure fall risk. Current gait analysis methods require overly complicated instrumentation and have not been tested for external factors such as walking surfaces that are encountered in the real-world, thus the results are difficult to extrapolate to real-world situations. Artificial intelligence approaches (in particular deep learning networks of varied architectures) to analyze data collected from wearable sensors were used to identify irregular surface exposure in a real-world setting. Thirty young adults wore six Inertial Measurement Unit (IMU) sensors placed on their body (right wrist, trunks at the L5/S1 level, left and right thigh, left and right shank) while walking over eight different surfaces commonly encountered in the living community as well as occupational settings. Three variations of deep learning models were trained to solve this walking surface recognition problem: 1) convolution neural network (CNN); 2) long short term memory (LSTM) network and 3) LSTM structure with an extra global pooling layer (Global-LSTM) which learns the coordination between different data streams (e.g. different channels of the same sensor as well as different sensors). Results indicated that all three deep learning models can recognize walking surfaces with above 0.90 accuracy, with the Global-LSTM yielding the best performance at 0.92 accuracy. In terms of individual sensors, the right thigh based Global-LSTM model reported the highest accuracy (0.90 accuracy). Results from this study provide further evidence that deep learning and wearable sensors can be utilized to recognize irregular walking surfaces induced motion alteration and applied to prevent falling injuries.

Analysis of anaerobic digester mixing: comparison of long shafted paddle mixing vs gas mixing.

The anaerobic digestion (AD) process is influenced by a variety of operation parameters, such as sludge rheology, mixing, temperature, solid retention time (SRT), hydraulic retention time (HRT) and solids concentration. The optimum in the mixing lies somewhere between no-mixing and continuous mixing, as the lack or excessive mixing can lead to poor AD performance instead. A three-dimensional computational fluid dynamics steady/unsteady model, incorporating the rheological properties of the sludge, was developed and applied to quantify mixing in a full-scale anaerobic digester. Mechanical and gas mixing solutions were taken into account, keeping constant the daily energy consumption. Results, consisting of velocity magnitude and patterns, dead zone formation and turbulence levels were discussed. Compared to the mechanical mixing, gas mixing had lower percentage of dead zones (about 5% against 50%), larger maximum velocity (about 3 m/s against 1 m/s) as well as larger turbulent kinetic energy levels (0.24 m2/s2 against 0.001 m2/s2).

Lung recruitment: What has computed tomography taught us in the last decade?

Although chest X-ray remains a fundamental lung imaging technique, through the years, CT scan has significantly improved our knowledge of the pathophysiological process and currently is the reference lung imaging tool for both a visual and quantitative computer-based analysis. The application of lung CT in the early phase of ARDS has led to changes in the clinical management in up of thirty percent of the patients. Although CT requires the transportation of the patient to the radiological department and exposes the patient to high dose of radiation, given the several information that CT can offer, it should be applied at least one time, in the early phase in all ARDS patients. CT plays an irreplaceable role to describe and assess the lung recruitability and to help a more physiological setting of mechanical ventilation.

Easy Printing of High Viscous Microdots by Spontaneous Breakup of Thin Fibers.

Electrohydrodynamic jetting is emerging as a successful technique for printing inks with resolutions well beyond those offered by conventional inkjet printers. However, the variety of printable inks is still limited to those with relatively low viscosities (typically <20 mPa s) due to nozzle clogging problems. Here, we show the possibility of printing ordered microdots of high viscous inks such as poly(lactic-co-glycolic acid) (PLGA) by exploiting the spontaneous breakup of a thin fiber generated through nozzle-free pyro-electrospinning. The PLGA fiber is deposited onto a partially wetting surface, and the breakup is achieved simply by applying an appropriate thermal stimulation, which is able to induce polymer melting and hence a mechanism of surface area minimization due to the Plateau-Rayleigh instability. The results show that this technique is a good candidate for extending the printability at the microscale to high viscous inks, thus extending their applicability to additional applications, such as cell behavior under controlled morphological constraints.

Forward electrohydrodynamic inkjet printing of optical microlenses on microfluidic devices.

We report a novel method for direct printing of viscous polymers based on a pyro-electrohydrodynamic repulsion system capable of overcoming limitations on the material type, geometry and thickness of the receiving substrate. In fact, the results demonstrate that high viscosity polymers can be easily manipulated for optical functionalizing of lab-on-a-chip devices through demonstration of direct printing of polymer microlenses onto microfluidic chips and optical fibre terminations. The present system has great potential for applications from biomolecules to nano-electronics. Moreover, in order to prove the effectiveness of the system, the optical performance of such microlenses has been characterized by testing their imaging capabilities when the fibroblast cells were allowed to flow inside the microfluidic channel, showing one of their possible applications on-board a LoC platform.

Maxillofacial trauma in the emergency department: pearls and pitfalls in airway management.

Maxillofacial trauma poses a challenge for the anesthesiologist because injuries can often compromise the patient's airways. Airway maintenance is the first step in the American College of Surgeons Advance Trauma Life Support (ATLS®) protocol. However, clinical dilemmas may arise about the best way to manage a potentially life-threatening injury. There are no recommendations about the best time to intubate, the warning signs for deciding to intubate, or which device should be used when difficulty is expected. In this context the ATLS® approach is important but not sufficient. It is also necessary to recognize and be able to manage specific problems in this scenario where clinical priorities may be conflicting, may suddenly change or may be hidden. This clinical review discusses the complexity of this scenario, providing an overview of the conditions at greatest risk for airway obstruction and the options for airway management, on the basis of the recent literature. Clinicians must recognize the milestones and pitfalls of this topic in order to adopt a systematic approach for airway management, to identify specific characteristics associated with it, and to establish the utility of different instruments for airway management.

Early outcome of liver transplantation performed with organs procured from brain death donors with transient or sustained cardio-circulatory collapse.

BACKGROUND: Aim of this study was to compare early graft function after transplantation of recipients transplanted with livers procured from donors after brain death who experienced transient or sustained cardio-circulatory collapse. METHODS: We retrospectively analysed patients who underwent liver transplantation (LTx) at our Institution from January 2010 to May 2012. Recipients were divided into 3 groups: those who received livers from brain death donors who experienced reversible cardio-circulatory arrest before organ procurement (RCA); those who experienced sustained cardio-circulatory collapse, treated with extra-corporeal membrane oxygenation support as rescue therapy of refractory cardiogenic shock (ECMO). Standard donors were considered as reference group (REF). Postoperative graft function, Primary Non-Function (PNF), and complications during the first 30 days were analysed. RESULTS: 102 LTx were analysed (76 REF, 22 RCA and 4 ECMO). The main cause of donor's death was post-anoxic coma in RCA and ECMO, cerebrovascular accident in REF. SGOT in REF, RCA, and ECMO donors were 27 [17-43], 54 [34-92], 716 [190-962] respectively, SGPT 17 [12-34], 46 [27-73], 84 [51-175] UI/L respectively, both P<0.01. All recipients had similar SGOT (P=0.48), SGPT (P=0.75) and Model for End-Stage Liver Disease scores (P=0.98) before LTx; similar graft cold and warm ischemia time and serum lactate levels at the end of surgery. After LTx, Intensive Care Unit stay and the incidence of PNF were similar. CONCLUSION: The use of livers procured from donors after brain death that experienced transient or sustained cardio-circulatory collapse was associated with early graft function comparable to that of standard donors.

Active accumulation of very diluted biomolecules by nano-dispensing for easy detection below the femtomolar range.

Highly sensitive detection of biomolecules is of paramount interest in many fields including biomedicine, safety and eco-pollution. Conventional analyses use well-established techniques with detection limits ~1 pM. Here we propose a pyro-concentrator able to accumulate biomolecules directly onto a conventional binding surface. The operation principle is relatively simple but very effective. Tiny droplets are drawn pyro-electro-dynamically and released onto a specific site, thus increasing the sensitivity. The reliability of the technique is demonstrated in case of labelled oligonucleotides diluted serially. The results show the possibility to detect very diluted oligonucleotides, down to a few hundreds of attomoles. Excellent results are shown also in case of a sample of clinical interest, the gliadin, where a 60-fold improved detection limit is reached, compared with standard ELISA. This method could open the way to a mass-based technology for sensing molecules at very low concentrations, in environmental as well as in diagnostics applications.

Mechanistic evaluation of the transfection barriers involved in lipid-mediated gene delivery: interplay between nanostructure and composition.

Here we present a quantitative mechanism-based investigation aimed at comparing the cell uptake, intracellular trafficking, endosomal escape and final fate of lipoplexes and lipid-protamine/deoxyribonucleic acid (DNA) (LPD) nanoparticles (NPs) in living Chinese hamster ovary (CHO) cells. As a model, two lipid formulations were used for comparison. The first formulation is made of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic lipid dioleoylphosphocholine (DOPC), while the second mixture is made of the cationic 3ß-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine (DOPE). Our findings indicate that lipoplexes are efficiently taken up through fluid-phase macropinocytosis, while a less efficient uptake of LPD NPs occurs through a combination of both macropinocytosis and clathrin-dependent pathways. Inside the cell, both lipoplexes and LPD NPs are actively transported towards the cell nucleus, as quantitatively addressed by spatio-temporal image correlation spectroscopy (STICS). For each lipid formulation, LPD NPs escape from endosomes more efficiently than lipoplexes. When cells were treated with DOTAP-DOPC-containing systems the majority of the DNA was trapped in the lysosome compartment, suggesting that extensive lysosomal degradation was the rate-limiting factors in DOTAP-DOPC-mediated transfection. On the other side, escape from endosomes is large for DC-Chol-DOPE-containing systems most likely due to DOPE and cholesterol-like molecules, which are able to destabilize the endosomal membrane. The lipid-dependent and structure-dependent enhancement of transfection activity suggests that DNA is delivered to the nucleus synergistically: the process requires both the membrane-fusogenic activity of the nanocarrier envelope and the employment of lipid species with intrinsic endosomal rupture ability.

Quantitative measurement of intracellular transport of nanocarriers by spatio-temporal image correlation spectroscopy.

Spatio-temporal image correlation spectroscopy (STICS) is a powerful technique for assessing the nature of particle motion in complex systems although it has been rarely used to investigate the intracellular dynamics of nanocarriers so far. Here we introduce a method to characterize the mode of motion of nanocarriers and to quantify their transport parameters on different length scales from single-cell to subcellular level. Using this strategy we were able to study the mechanisms responsible for the intracellular transport of DOTAP-DOPC/DNA and DC-Chol-DOPE/DNA lipoplexes in CHO-K1 live cells. Measurement of both diffusion coefficients and velocity vectors (magnitude and direction) averaged over regions of the cell revealed the presence of distinct modes of motion. Lipoplexes diffused slowly on the cell surface (diffusion coefficient, D ≈ 0.003 µm2/s). In the cytosol, the lipoplexes' motion was characterized by active transport with average velocity ν ≈ 0.03 µm/s and random motion. The method permitted us to generate intracellular transport map showing several regions of concerted motion of lipoplexes.

Spontaneous assembly of carbon-based chains in polymer matrixes through surface charge templates.

Stable chains of carbon-based nanoparticles were formed directly in polymer matrixes through an electrode-free approach. Spontaneous surface charges were generated pyroelectrically onto functionalized ferroelectric crystals, enabling the formation of electric field gradients that triggered the dipole-dipole interactions responsible for the alignment of the particles, while embedded in the polymer solution. The phenomenon is similar to the dielectrophoretic alignment of carbon nanotubes reported in the literature. However, here the electric fields are generated spontaneously by a simple heat treatment that, simultaneously, aligns the particles and provides the energy necessary for curing the host polymer. The result is a polymer sheet reinforced with well-aligned chains of carbon-based particles, avoiding the invasive implementation of appropriate electrodes and circuits. Because polymers with anisotropic features are of great interest for enhancing the thermal and/or the electrical conductivity, the electrode-free nature of this technique would improve the scaling down and the versatility of those interconnections that find applications in many fields, such as electronics, sensors, and biomedicine. Theoretical simulations of the interactions between the particles and the charge templates were implemented and appear in good agreement with the experimental results. The chain formation was characterized by controlling different parameters, including surface charge configuration, particle concentration, and polymer viscosity, thus demonstrating the reliability of the technique. Moreover, micro-Raman spectroscopy and scanning electron microscopy were used for a thorough inspection of the assembled chains.

Graded-size microlens array by the pyro-electrohydrodynamic continuous printing method.

In the present work, the pyro-electrohydrodynamic technique was used for the realization of tunable-size microlens arrays. Poly(methyl methacrylate) dissolved in different solvent mixtures was used as the polymeric material for the realization of the microstructures. By controlling the experimental parameters and in particular, the volume of the drop reservoir, graded-size square arrays of tens of microlenses with focal length in the range 1.5-3 mm were produced. Moreover, the optical quality and geometrical features were investigated by profilometric and interferometric analysis.