ACUTE KIDNEY INJURY IN SEVERE PNEUMONIA ASSOCIATED WITH COVID-19

The clinical and epidemiological features of acute kidney injury in severe and extremely severe pneumonia associated with coronavirus disease-2019 (COVID-19) are considered. An observational prospective study was conducted with the inclusion of 117 patients, including 75 men and 42 women, suffering from severe and extremely severe pneumonia associated with COVID-19, who were treated in the intensive care unit of the 1586th Military Clinical Hospital in 2020–2022. Acute kidney injury was diagnosed in 21 (17.9%) patients (stage 1 in 10, stage 2 in 4, and stage 3 in 7 patients), kidney dysfunction was recorded in 22 (8.8%) patients (serum creatinine was higher than normal, but does not reach the diagnostic criteria of Kidney Disease Improving Global Outcomes). Four patients underwent renal replacement therapy. The probability of kidney damage increases with age (the average age of the patients with acute kidney damage is 65 (58;71) years, and those without acute kidney damage was 47.5 (41;55) years;p = 0.0001). Compared with patients without acute kidney injury, patients with acute kidney injury scored higher on the scales NEW (p = 0.000975), SMRT-CO (p = 0.011555), and Sequential Organ Failure Assessment (p = 0.000042). Among those suffering from acute kidney injury, significantly more pronounced manifestations of systemic inflammation were determined (leukocytes, p = 0.047324;platelets, p = 0.001230;ferritin, p = 0.048614;and D-dimer, p = 0.004496). In the general cohort, the mortality rate was 22.2%, whereas a significant intergroup difference in mortality was observed, i.e., 52.4% in patients with acute kidney injury and 15.62% in those without acute kidney injury (Chi-squared criterion, 13.468;p < 0.001). Invasive artificial lung ventilation was performed in 19.66% of the patients, and a significant intergroup difference was identified, with 66.7% in patients with acute kidney injury and 9.38% in patients without acute kidney injury (Chi-squared criterion, 35.810;p < 0.001). The durations of treatment in the intensive care unit in patients with and without acute kidney injury were 9 (7;14) and 6 (4;10) days, respectively. After the treatment, all patients with acute kidney injury had fully recovered kidney function upon discharge. In general, acute kidney injury occurs in almost every fifth patient with severe and extremely severe pneumonia associated with COVID-19, aggravates the condition of patients, and increases mortality. The alertness of doctors regarding acute kidney injury and early diagnosis and timely nephroprotective treatment may reduce the possibility of adverse disease outcomes. All rights reserved © Eco-Vector, 2022.

A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

Severe course of diabetic ketoacidosis due to new coronavirus infection in older children (clinical cases).

The risk of severe type I diabetes mellitus in children with new coronavirus infection (COVID-19) is extremely high, which is associated, with a high risk of intracranial hypertension, cerebral edema and multiple organ dysfunction, syndrome. On the example of a clinical case, the features of the course of diabetic ketoacidosis and. intensive care measures in children with COVID-19 were considered. The main data of the history and clinical and laboratory examination are reflected, specialattention is paid to the applied aspects of therapy, it was noted that with a severe course of a new coronavirus infection and diabetic ketoacidosis, the risk of developing cerebral injury, acute kidney injury and. thromboembolic complications is quite high, which, may require artificial lung ventilation, for the purpose of cerebral protection, renal replacement therapy and. the use of anticoagulants. The new coronavirus infection is a risk factor for the severe course of diabetic ketoacidosis in children with type I diabetes, regardless of the age of the child, which is the basis for clinicalalertness in order to timely identify and treat potential life-threatening complications.Copyright © 2022 Authors. All rights reserved.

Work-in-Progress: DIY Ventilator - A CoVID-19 Action

In the Covid-19 pandemic, ventilators became scarce, especially in countries with lower medical standards. A special project has managed to develop a complete ventilator as a kit using cheap parts and 3D printers. In the first two phases of the project a demonstrator has been developed which allows first tests. With hands-on experiments, one can already control the ventilator together with an artificial lung and learn how the ventilator works and what types of pumps, sensors, and electronic components are necessary for this. Due to its multidisciplinary character this project provides an excellent basis for the elaboration of educational and instructional material. Disciplines addressed comprise among others: informatics, physics, mathematics, biochemistry, medicine, material science, and electronics. In addition, the use of tools is demonstrated on a wide range covering 3D printing, IDEs for software development, wiring and soldering, etc. The knowledge gained through this project could be used for setting up a startup enterprise or as reference when starting research in the Edge Computing or IoT domain. The education and training will be carried out in small groups (four persons ideally) using a system for blended learning. It is envisaged to use the Mediathread Development [1] from the Columbia University which provides an excellent framework for the flipped classroom approach. Besides the academic domain also industries are the target for using the educational material which will be delivered by the project. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Synthetic Lung Surfactant Treatment for COVID-19 Pneumonia

COVID-19 has led to morbidity in millions of patients, ranging from mild flu-like symptoms to severe respiratory failure, necessitating oxygen supplementation and mechanical ventilation, and ultimately death. The SARS-CoV-2 virus reacts with angiotensin-converting enzyme 2 (ACE2) molecules that are especially found in alveolar epithelial type 2 cells in the lungs and thereby causes a loss in lung surfactant, a protein-lipid mixture that is crucial for both native immunity and reduction of surface ten-sion in the lung alveoli. Lung surfactant insufficiency results in atelectasis and loss of functional lung tissue amid an inflammatory storm and may be countered by treating COVID-19 pneumonia patients with exogenous lung surfactant, preferably by aerosol delivery of a novel dry powder synthetic lung sur-factant. More research on timing, dosing, and delivery of synthetic lung surfactant in patients with COVID-19 pneumonia is of crucial importance to implement this approach in clinical practice.Copyright © 2021 Bentham Science Publishers.

Devices with Fuzzy Logic Control of Artificial Lung Ventilation

This article presents the development of a ventilator and its control algorithm. The main feature of the developed ventilator is compressed by a pneumatic drive. The control algorithm is based on the adaptive fuzzy inference system (ANFIS), which integrates the principles of fuzzy logic. The paper also presents a simulation model to test the designed control approach. The results of the experiment provide verification of the developed control system. The novelty of the article is, on the one hand, the implementation of the ANFIS controller, pressure control, with a description of the training process. On the other hand, in the article presented a draft ventilator with a detailed description of the hardware and control system. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The results of thrombectomy from the arteries of the lower extremities in patients infected with SARS-CoV-2 Omicron variant with different severity of respiratory failure.

GOAL: Analysis of the results of thrombectomy from the arteries of the lower extremities in patients with COVID-19 against the background of different severity of respiratory failure. MATERIALS AND METHODS: This retrospective, cohort, comparative study for the period from 05/01/2022 to 20/07/2022 included 305 patients with acute thrombosis of the arteries of the lower extremities against the background of the course of COVID-19 (SARS-CoV-2 Omicron variant). Depending on the type of oxygen support, 3 groups of patients were formed: group 1 (n = 168) - oxygen insufflation through nasal cannulas; group 2 (n = 92) - non-invasive lung ventilation; and group 3 (n = 45) - artificial lung ventilation. RESULTS: Myocardial infarction and ischemic stroke were not detected in the total sample. The highest number of deaths (group 1: 5.3%, n = 9; group 2: 72.8%, n = 67; group 3: 100%, n = 45; p < 0.0001), rethrombosis (group 1 : 18.4%, n = 31; group 2: 69.5%, n = 64; group 3: 91.1%, n = 41; p < 0.0001), and limb amputations (group 1: 9.5%, n = 16; group 2: 56.5%, n = 52; group 3: 91.1%, n = 41; p < 0.0001) was recorded in group 3 (ventilated) patients. CONCLUSION: In patients infected with COVID-19 and on artificial lung ventilation, a more aggressive course of the disease is noted, expressed in an increase in laboratory parameters (C-reactive protein, ferritin, interleukin-6, and D-dimer) of the degree of pneumonia (CT-4 in overwhelming number) and localization of thrombosis of the arteries of the lower extremities, mainly in the tibial arteries.

Hemocompatibility challenge of membrane oxygenator for artificial lung technology.

The artificial lung (AL) technology is one of the membrane-based artificial organs that partly augments lung functions, i.e. blood oxygenation and CO2 removal. It is generally employed as an extracorporeal membrane oxygenation (ECMO) device to treat acute and chronic lung-failure patients, and the recent outbreak of the COVID-19 pandemic has re-emphasized the importance of this technology. The principal component in AL is the polymeric membrane oxygenator that facilitates the O2/CO2 exchange with the blood. Despite the considerable improvement in anti-thrombogenic biomaterials in other applications (e.g., stents), AL research has not advanced at the same rate. This is partly because AL research requires interdisciplinary knowledge in biomaterials and membrane technology. Some of the promising biomaterials with reasonable hemocompatibility - such as emerging fluoropolymers of extremely low surface energy - must first be fabricated into membranes to exhibit effective gas exchange performance. As AL membranes must also demonstrate high hemocompatibility in tandem, it is essential to test the membranes using in-vitro hemocompatibility experiments before in-vivo test. Hence, it is vital to have a reliable in-vitro experimental protocol that can be reasonably correlated with the in-vivo results. However, current in-vitro AL studies are unsystematic to allow a consistent comparison with in-vivo results. More specifically, current literature on AL biomaterial in-vitro hemocompatibility data are not quantitatively comparable due to the use of unstandardized and unreliable protocols. Such a wide gap has been the main bottleneck in the improvement of AL research, preventing promising biomaterials from reaching clinical trials. This review summarizes the current state-of-the-art and status of AL technology from membrane researcher perspectives. Particularly, most of the reported in-vitro experiments to assess AL membrane hemocompatibility are compiled and critically compared to suggest the most reliable method suitable for AL biomaterial research. Also, a brief review of current approaches to improve AL hemocompatibility is summarized. STATEMENT OF SIGNIFICANCE: The importance of Artificial Lung (AL) technology has been re-emphasized in the time of the COVID-19 pandemic. The utmost bottleneck in the current AL technology is the poor hemocompatibility of the polymer membrane used for O2/CO2 gas exchange, limiting its use in the long-term. Unfortunately, most of the in-vitro AL experiments are unsystematic, irreproducible, and unreliable. There are no standardized in-vitro hemocompatibility characterization protocols for quantitative comparison between AL biomaterials. In this review, we tackled this bottleneck by compiling the scattered in-vitro data and suggesting the most suitable experimental protocol to obtain reliable and comparable hemocompatibility results. To the best of our knowledge, this is the first review paper focusing on the hemocompatibility challenge of AL technology.

Design and Efficacy of a Novel Low-Cost Ventilator: A Feasibility Study on Artificial Lungs

RATIONALE: The emergent need for ventilators amidst the COVID-19 pandemic has catalyzed production of innovative ventilator designs in hopes to optimize supply, manufacturing, ease of use, and cost in disaster situations. In efforts to identify a feasible solution to combat global healthcare disparities, we aimed to develop a ventilator that could provide consistent, reliable, and highquality ventilatory support at less than 10% the price of current Food and Drug Administration (FDA)-cleared ventilators. METHODS: We created a novel, low-cost ventilator, which uses 'choked flow' to perform volume assist-control ventilation. Choked flow is a method of controlling mass flow utilized in rocket engines and spacecraft, which uses changes in upstream pressure and orifice plate diameter to impact flow rate. We compared the efficacy and safety of the novel ventilator to a FDAcleared ventilator by testing the ventilator across 8 test cases on a lung simulator, with each test case trial lasting for at least 24 breath cycles. Delivered tidal volumes, peak inspiratory pressures, and plateau pressures were measured, and linear regression models were used to assess for non-inferiority of the novel ventilator as compared to that of a FDA-cleared ventilator. RESULTS: For each of the test cases, the standard deviation for the tidal volumes delivered by the novel ventilator ranged from 0.11 to 0.80 milliliters (ml), or less than 0.01% of the mean tidal volume value. There was also minimal breath-to-breath variation for both plateau and peak inspiratory pressures, with a maximum standard deviation for both plateau and peak inspiratory pressures of 0.15 centimeters of water. The novel ventilator was found to be non-inferior to the FDA-cleared ventilator for delivered tidal volumes, with a maximum difference in the volumes delivered between the two ventilators of less than 7 ml for all test cases (Figure 1). Plateau pressures were also found to be non-inferior across all test cases, while peak inspiratory pressures were found to be non-inferior in 6 of the 8 test cases when compared to those of the FDA-cleared ventilator.

The microfluidic artificial lung: Mimicking nature's blood path design to solve the biocompatibility paradox.

The increasing prevalence of chronic lung disease worldwide, combined with the emergence of multiple pandemics arising from respiratory viruses over the past century, highlights the need for safer and efficacious means for providing artificial lung support. Mechanical ventilation is currently used for the vast majority of patients suffering from acute and chronic lung failure, but risks further injury or infection to the patient's already compromised lung function. Extracorporeal membrane oxygenation (ECMO) has emerged as a means of providing direct gas exchange with the blood, but limited access to the technology and the complexity of the blood circuit have prevented the broader expansion of its use. A promising avenue toward simplifying and minimizing complications arising from the blood circuit, microfluidics-based artificial organ support, has emerged over the past decade as an opportunity to overcome many of the fundamental limitations of the current standard for ECMO cartridges, hollow fiber membrane oxygenators. The power of microfluidics technology for this application stems from its ability to recapitulate key aspects of physiological microcirculation, including the small dimensions of blood vessel structures and gas transfer membranes. An even greater advantage of microfluidics, the ability to configure blood flow patterns that mimic the smooth, branching nature of vascular networks, holds the potential to reduce the incidence of clotting and bleeding and to minimize reliance on anticoagulants. Here, we summarize recent progress and address future directions and goals for this potentially transformative approach to artificial lung support.

Optimizing Control of IOT Device using Traditional Machine Learning Models and Deep Neural Networks

With the increasing threat of Covid-19 and now omicron infection across the world among people, there has been a significant surge in the demand for a fully-automated, self-controlled or mechanized ventilator which can provide sufficient air-pressure to weak human lungs continuously. It is our humble endeavor to mitigate the effects caused due to handful of trained-physicians over countless untreated patients and lack of enough health-infrastructure facilities to support in the time of dire need. We all dread losing another precious life on earth due to any one of the above mentioned reason. We have tried simulating the observations obtained from a lab-developed mechanical ventilator system under different lung settings. After preprocessing this dataset using NLP, training data is analysed to study the correlation between observations from numerous attributes. A couple of Machine Learning (LR, RF, SVM, LGBM) and Deep Learning (MLP, LSTM, Bi-LSTM) algorithms have been deployed to train our model individually, out of which Bi-LSTM performed exceptionally well above others. However, only after exhaustive clinical trials and recommendations a large of number of patients on life-support can get a new life through the large practical application of this device, in the near future. © 2022 IEEE.

Electron Microscopic Confirmation of Anisotropic Pore Characteristics for ECMO Membranes Theoretically Validating the Risk of SARS-CoV-2 Permeation.

The objective of this study is to clarify the pore structure of ECMO membranes by using our approach and theoretically validate the risk of SARS-CoV-2 permeation. There has not been any direct evidence for SARS-CoV-2 leakage through the membrane in ECMO support for critically ill COVID-19 patients. The precise pore structure of recent membranes was elucidated by direct microscopic observation for the first time. The three types of membranes, polypropylene, polypropylene coated with thin silicone layer, and polymethylpentene (PMP), have unique pore structures, and the pore structures on the inner and outer surfaces of the membranes are completely different anisotropic structures. From these data, the partition coefficients and intramembrane diffusion coefficients of SARS-CoV-2 were quantified using the membrane transport model. Therefore, SARS-CoV-2 may permeate the membrane wall with the plasma filtration flow or wet lung. The risk of SARS-CoV-2 permeation is completely different due to each anisotropic pore structure. We theoretically demonstrate that SARS-CoV-2 is highly likely to permeate the membrane transporting from the patient's blood to the gas side, and may diffuse from the gas side outlet port of ECMO leading to the extra-circulatory spread of the SARS-CoV-2 (ECMO infection). Development of a new generation of nanoscale membrane confirmation is proposed for next-generation extracorporeal membrane oxygenator and system with long-term durability is envisaged.

Bioengineering Progress in Lung Assist Devices.

Artificial lung technology is advancing at a startling rate raising hopes that it would better serve the needs of those requiring respiratory support. Whether to assist the healing of an injured lung, support patients to lung transplantation, or to entirely replace native lung function, safe and effective artificial lungs are sought. After 200 years of bioengineering progress, artificial lungs are closer than ever before to meet this demand which has risen exponentially due to the COVID-19 crisis. In this review, the critical advances in the historical development of artificial lungs are detailed. The current state of affairs regarding extracorporeal membrane oxygenation, intravascular lung assists, pump-less extracorporeal lung assists, total artificial lungs, and microfluidic oxygenators are outlined.

The Roles of Membrane Technology in Artificial Organs: Current Challenges and Perspectives.

The recent outbreak of the COVID-19 pandemic in 2020 reasserted the necessity of artificial lung membrane technology to treat patients with acute lung failure. In addition, the aging world population inevitably leads to higher demand for better artificial organ (AO) devices. Membrane technology is the central component in many of the AO devices including lung, kidney, liver and pancreas. Although AO technology has improved significantly in the past few decades, the quality of life of organ failure patients is still poor and the technology must be improved further. Most of the current AO literature focuses on the treatment and the clinical use of AO, while the research on the membrane development aspect of AO is relatively scarce. One of the speculated reasons is the wide interdisciplinary spectrum of AO technology, ranging from biotechnology to polymer chemistry and process engineering. In this review, in order to facilitate the membrane aspects of the AO research, the roles of membrane technology in the AO devices, along with the current challenges, are summarized. This review shows that there is a clear need for better membranes in terms of biocompatibility, permselectivity, module design, and process configuration.

Artificial lungs--Where are we going with the lung replacement therapy?

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy.