Comment: Balanced Salt Solutions for Critically Ill Patients: Nonplused and Back to Basics.

The analysis of trial results of the intravenous fluids pharmacodynamics revealed problems common to all studies, such as varying study designs, clinical discretion for treatments, and heterogeneous patients. We believe that in the methodology of future research it is also necessary to pay due attention to the actual rather than theoretical physicochemical parameters of the solutions used, such as osmolality, pH, and potential excess of bases. Paying attention to these parameters of intravenous fluids will be useful for assessing their role in producing pharmacodynamic effects in critically ill patients.

Cardiology, respiratory failure, and tolerance of hypoxia in the context of COVID-19: a multidisciplinary perspective.

After reading with great interest the article entitled: "Exploring the impact of the COVID-19 pandemic on provision of cardiology services: a scoping review" redacted by Farah Yasmin et al., published by Reviews in Cardiovascular Medicine, we would like to add the following thoughts. Acute respiratory distress syndrome (ARDS) in Coronavirus disease 2019 (COVID-19) and pulmonary insufficiency reduces blood oxygen saturation and results in hypoxia. Therefore, the determining factor in the survival of patients with COVID-19 is their resistance to hypoxia. At the same time, it is the cardiovascular system that is an important and very sensitive link in the human adaptation to hypoxia. That is why it is necessary to carefully study the relationship between diseases of the heart, blood vessels, the reactivity of the cardiovascular system to hypoxia, and mortality in patients who develop ARDS with COVID-19.

Stroke, Thrombosis, Bleeding and Addiction to Anticoagulants in the Context of Course Therapy: A Pharmacologic Perspective.

After reading with great interest the article entitled: "Non-vitamin K antagonist oral anticoagulants (NOACs) do not increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation: insights from multi-source medical data" authored by Zhi-Chun Gu et al. and published by Reviews in Cardiovascular Medicine, we would like to add the following thoughts. Oral anticoagulants are generally accepted in patients with non-valvular atrial fibrillation to prevent thrombosis and stroke. Since anticoagulants are taken daily for many months in these patients, we cannot rule out chronic poisoning and the development of liver failure. But another complication is just as likely, that being bleeding. Thus, the determining risk factor for the health of patients with a prolonged course of oral anticoagulants is hypofunctional activity of the blood coagulation system, which remains at the same level throughout the course of treatment. At the same time, it is the activity of the blood coagulation system that is an important and very sensitive link of adaptation to various external and internal factors, including anticoagulants. The fact is that regular and prolonged oral use of anticoagulants is likely to develop and tolerance to them. That is why it is necessary to carefully study the relationship between the dose of oral anticoagulants, the duration of pharmacotherapy and the development of thrombosis (bleeding) in patients with non-valvular atrial fibrillation.

Dynamics of Local Temperature in the Fingertips After the Cuff Occlusion Test: Infrared Diagnosis of Adaptation Reserves to Hypoxia and Assessment of Survivability of Victims at Massive Blood Loss.

Background: Since changes in the tone and size of the lumen of peripheral blood vessels with massive blood loss are part of the mechanism of adaptation to hypoxia, which automatically changes the flow of warm blood to the fingertips, it was assumed that infrared thermography of the fingertips can reveal the dynamics of heat release in them, reflecting the reactivity of peripheral blood vessels and adaptation to hypoxia. It was assumed that the cuff occlusion test (COT) would assess the available reserves of adaptation to hypoxia and improve the accuracy of resistance to hypoxia and the prognosis of survival in massive blood loss. Methods: The temperature change in the fingertips before and after the application of COT in the corresponding hand was studied in healthy adult volunteers, donors after donating 400 mL of blood and in victims with blood loss of less than or more than 35%. Results: During COT, the temperature in the fingers of the ischemic hand decreased in all the subjects. After COT the temperature in the fingers rose above the baseline level in healthy volunteers and in donors who donated 400 mL of blood, but did not increase in most patients with massive blood loss, of which some patients died despite the treatment. Conclusions: We report the dynamics of local temperature in the finger pads after the COT in healthy adult volunteers, in donors after they donated 400 mL of venous blood each, and in victims with massive blood loss less than or greater than 35%. It is shown that the detection of local hyperthermia in the finger pads after occlusion is a sign of good adaptation to hypoxia and the probability of survivability of the victim with massive blood loss.

Brain hypoxia caused by respiratory obstruction which should not be forgotten in COVID-19 disease.

DISCUSSION: None. The authors declare that there are no potential conflicts of interest.

Using Ultrasonography to Determine Optimal Head-down Tilt Position Angle in Patients before Catheterization of the Internal Jugular Vein.

CONTEXT: It is believed that 15°-25° head-down tilt position increases the internal jugular vein cross-sectional area (IJV CSA). The increase in IJV CSA before puncture reduces the risk of its perforation. This pattern was not observed in all patients. We assumed that the absence of respiratory-based IJV excursion is one of the criteria of head-down tilt position effectiveness. AIMS: The aim of this study is to determine the head-down tilt angle, which ensures the absence of the respiratory-based IJV excursion. SUBJECTS AND METHODS: Prospective study included twenty adult patients. The IJVs scanning was carried out in 1 min after placing the patients in a horizontal position on their back and in 1 min after placing them in the head-down tilt position at 5°, 10°, 15°, and 20° tilt angles. RESULTS: We found that collapsibility index of <9% indicating the absence of respiratory-based IJV excursion was recorded in 25% of patients in the horizontal supine position. In this case, placing the patients in the Trendelenburg position for IJV catheterization may not be indicated. In 65% of the patients, the respiratory-based excursion was not observed at 10° head-down tilt position. Only 35% of the patients required 15° head-down tilt position. CONCLUSIONS: In clinical settings, the disappearance of respiratory-based vein excursion on the ultrasound scanner screen can be considered as criteria of the head-down tilt position effectiveness.

The dynamics of changing internal jugular veins diameter based on increasing head elevation angle.

CONTEXT: Venous outflow from the cranial cavity occurs mainly through the internal jugular vein (IJV). The increase in venous outflow through IJV is possible by head elevation. IJV collapse may indicate the reduction of blood volume in the vein and show the head elevation effectiveness. AIMS: The aim of this study is to examine the impact of head elevation on IJV size. SUBJECTS AND METHODS: IJV ultrasound scanning in 31 healthy volunteers was carried after gradual head elevation at 15°, 30°, and 45°. Maximum and minimum IJV diameters were recorded. Mean ± standard deviation, median, range, and collapsibility index were calculated. RESULTS: Thirty-one volunteers were involved (19 males), their average age was 37.0 ± 11.5 years. Increasing the head elevation angle by 15°, 30° and 45° resulted in a decrease in IJV diameter in the right and left sides in all patients. The occurrence of the vein walls collapse corresponds to the collapsibility index equal to 100%. The results showed that 100% collapsibility index was recorded in 6 patients (19%) at 15° head elevation, in 12 patients (39%) at 30°, in 11 patients (35%) at 45°. In two volunteers (6%), 100% collapsibility index was not recorded even at maximum 45° head elevation. CONCLUSIONS: Ultrasound IJV scanning during gradual head elevation together with the collapsibility index calculation could be useful guidance for the venous outflow assessment. In order to prove and extend the study findings, more research is needed.

Thermal imaging of local skin temperature as part of quality and safety assessment of injectable drugs.

Injection of high-quality drugs can occasionally cause unexpected and unexplained local complications. As the current standard for drug quality control does not include an assessment of the local irritation effects of drugs, this effect may cause postinjection complications. Simultaneously, local irritation effects of the drugs can be assessed based on local tissue inflammation. The dynamics of local temperature can assess inflammation. Infrared monitoring of local skin temperature dynamics at subcutaneous, intramuscular, and intravenous injection sites of drugs under experimental and clinical conditions can improve their quality and safety. Therefore, there is a need to include dynamic thermography in the standard of biological evaluation of the quality and safety of drugs in the dosage form "solution for injections." This eliminates the local irritation and necrotizing activity of drugs and minimizes the development of local pain syndrome, aseptic inflammation, necrosis, and abscess.

Effect of hydrogen peroxide on erythrocyte temperature in vitro.

Hydrogen peroxide (H2O2) is produced by most human cells. Cellular enzymes determine the features of the chemico-biological interaction between cells and hydrogen peroxide. The catalase is main intracellular enzyme that inactivates H2O2 in cells, in particular, erythrocytes. Catalase decomposes hydrogen peroxide into water and oxygen with the release of energy. However, until now, there is no convincing scientific data proving that the temperature of the cells changes when adding a solution of hydrogen peroxide. We conducted studies on how H2O2 solutions with different concentrations affect the change in erythrocytes temperature in vitro. Our results proved that toxic doses of hydrogen peroxide increase the temperature of red blood cells.

Modified Stange test gives new gynecological criteria and recommendations for choosing caesarean section childbirth.

Pregnancy and childbirth often threaten the life and health of the fetus. The greatest threat to the fetus during these periods is intrauterine hypoxia. The threat of intrauterine fetal hypoxia increases during natural childbirth and decreases during caesarean section. Therefore, it is no coincidence that the rate of C-section births is increasing worldwide. However, the generally accepted recommendations on the choice of caesarean delivery need to be clarified. A new test is needed to simulate intrauterine hypoxia and predict fetal survival during natural childbirth. Such a test would improve current C-section recommendations and newborn health outcomes. The most appropriate basis for such a functional test is the generally accepted Stange test. The fact is that the Stange test is a very easy to use and accurate functional test based on the duration of the longest breath hold. For more than 100 years, the Stange test has been successfully used to assess the adaptation reserves of adults to hypoxia in real time. The purpose of this letter is to present a new easy-to-use functional test designed to assess the resistance to hypoxia not only of the pregnant woman, but also of her fetus in real time. This new test could be a new vector in obstetric practice aimed at improving neonatal health and reducing infant mortality during delivery.

COVID-19: Artificial sputum, respiratory obstruction method and screening of pyolitic and antihypoxic drugs.

COVID-19 causes non-specific pneumonia, which has become a new cause of hypoxia, leading to the death of many patients. Today, there are no effective drugs that provide an urgent increase in blood oxygenation. Therefore, it is urgently necessary to develop drugs to increase blood oxygenation in order to save the lives of patients with the new coronavirus infection. Since hypoxia develops in this disease due to the blockage of respiratory tract with viscous mucus and sputum, an appropriate experimental model is needed for screening and finding new drugs. However this model is yet missing. Therefore, the development of an experimental model of respiratory obstruction by sputum with traces of blood can accelerate the discovery of drugs that eliminate hypoxia and prevent the death of patients with nonspecific pneumonia complicated by respiratory obstruction. The purpose of this letter was to present a model for evaluating the biological activity of drugs, which can become a new vector for the development of effective ways to increase blood oxygenation across pulmonary and save the lives of patients with severe atypical pneumonia complicated by respiratory obstruction in COVID-19.

Spray with Nitric Oxide Donor Accelerates Wound Healing: Potential Off-the-Shelf Solution for Therapy?

BACKGROUND: Ditrosyl iron complexes (DNIC) are endogenous donors of nitric oxide. The possibility of their application to stimulate regeneration has been studied for more than 15 years. However, the most effective dose and form of delivery have not yet been determined. PURPOSE: The aim of this research was to develop a spray form of DNIC that accelerates wound healing. METHODS: We prepared a series of DNIC sprays with spray dosages of 10, 50 and 100 µg. We modelled full-thickness skin wounds in 24 Wistar rats and treated them with distilled water (n = 6), 10 (n = 6), 50 (n = 6) and 100 µg (n = 6) for three post-operative days. On the fourth day, the excised wound tissues were studied by morphological, immunohistochemical and morphometric methods. RESULTS: We demonstrated that 50 µg of DNIC spray had the most beneficial effect on wound healing: the thickness of the granulation tissue layer was 140% higher, vimentin positive fibroblasts predominated and the intensity of inflammation was significantly lower than in the control. There was a dose-dependent decrease in the functional activity of mast cells in the experimental groups compared to the control. CONCLUSION: DNIC spray is a potential effective dosage form for the treatment of large-area skin lesions.

Current and emerging methods for treatment of hemoglobin related cutaneous discoloration: A literature review.

BACKGROUND: Currently, there is no available medication for immediate correction of bruise discoloration. Instead, makeup, cosmetic powders, concealers, and various traditional herbal remedies are used to mask discoloration. These approaches have no influence on the pathology behind the discoloration. The purpose of this study was to explore existing methods and current trends in correction of hemoglobin related cutaneous discoloration. METHODS: This paper describes the treatment methodologies available for proposed correction of hemoglobin related cutaneous discoloration. A thorough literature review was conducted to assess current knowledge of available treatments for bruise discoloration. RESULTS: current cosmetics being marketed under the names "Bleacher bruises," "Bleaching agents" and "Blood bleachers" addressing bruise related discoloration do not offer targeted pathological treatment. Several methods for immediate discoloration of the skin and nail plate in the area of bruising and hematoma were found, yet no method offered sufficient clinical data in support of its efficacy and safety. The intricate mechanisms of discoloration associated with hemoglobin extravascular deterioration are not targeted by any treatment method. Only one paper outlining the clinical application of bleaching agents was found. CONCLUSION: The primary blood pigments responsible for the discoloration in bruises include methemoglobin, oxyhemoglobin, carbohymoglobin, verdoglobin, biliverdin, and bilirubin. No existing method targets the degradation of hemoglobin in the area of ecchymosis. The efficacy of existing patented methods remains questionable and unsupported clinically. Future research should focus on developing a drug targeting hemoglobin derivatives, preventing discoloration at an early stage.

Oxygen Alkaline Dental's Cleaners from Tooth Plaque, Food Debris, Stains of Blood, and Pus: A Narrative Review of the History of Inventions.

OBJECTIVE: This review shows the history of inventions of devices, hygiene products, and methods of dissolution and removal of pus, sulfur plugs, blood crusts, and plaque. MATERIAL AND METHODS: The search for inventions was carried out in the databases, such as Google Patent, Google Scholar, Scopus, and PubMed. The key words used in this search were as follows: toothbrushes, toothpicks, toothpastes, plaque, cleaning products for teeth and dentures, teeth whiteners and dentures, bleach bruises and blood stains, pus, sulfur plugs, and pus solvents. A total of 24 inventions were evaluated for review. RESULTS: In recent years, hygiene products that quickly dissolve and bleach pus, sulfur plugs, blood stains, and plaque because of alkaline saponification of protein-lipid complexes and cold boiling inside the biological masses have been invented. Such an action has a heated above 37°C supersaturated sodium bicarbonate solutions containing hydrogen peroxide in moderate concentrations and gaseous oxygen under excessive pressure. Cold boiling inside the dense biological masses occurs under the action of catalase and/or due to the normalization of internal pressure in the solution. CONCLUSION: Alkalinity, hyperthermia, and hyperoxygenation of solutions with high internal pressure optimize whitening of teeth and dentures because of alkaline saponification and cold boiling.

Ultrasound-guided internal jugular vein cannulation in the obese patient in a forced semi-sitting position.

INTRODUCTION: Central venous cannulation may be difficult in morbidly obese patients. We present a case of successful right internal jugular vein catheterization under real-time ultrasound guidance in an obese patient in a forced semi-sitting position. CASE REPORT: A 43-year-old male patient with body mass of 182 kg (body mass index, 52.2 kg/m2) was admitted to the clinic 48 h after the trauma. The patient was in a forced semi-sitting position (37° head elevation). The patient was not able to perform the Valsalva maneuver. In the reported case, the lateral access for right internal jugular vein catheterization was chosen. We selected a lateral-oblique probe position for the ultrasound-guided internal jugular vein cannulation. Internal jugular vein catheterization was successful at the first attempt. CONCLUSION: Ultrasound imaging enables us to choose a desirable access for successful internal jugular vein cannulation in the obese patient without head-down tilt position. The lateral-oblique probe position for internal jugular vein cannulation may have advantages in certain clinical situations.

Changes in the Internal Size of the Jugular Vein in Adult Patients with Hypovolemia.

The present study is aimed at establishing the values of internal jugular vein (IJV) anterior-posterior and medial-lateral sizes in patients with hypovolemia. A total of 25 adult Intensive Care Unit patients with hypovolemia were studied. It was found that the anterior-posterior vein size in patients with hypovolemia was significantly less than medial-lateral size during inhalation and during exhalation as well (P < 0.05). Besides, the value of the anterior-posterior size (Dmin) <7 mm was recorded in 20 from 25 patients (80%). At the same time, the medial-lateral size (Dmin) <7 mm was recorded only in six patients (24%). In patients with hypovolemia, the medial-lateral diameter of IJV is more than its anterior-posterior diameter. These data might be useful for justifying the benefits of using lateral access for IJV catheterization under ultrasound imaging in patients with hypovolemia.

The off-label use of drugs for parenteral nutrition as a solvent of substances slightly soluble in water in pharmacological research.

Because of the problem to evaluate biological activity in water-soluble substances in all phases of preclinical and clinical studies, the research work enabled to develop the original solvent for poorly soluble compounds based on substances for parenteral nutrition. The main aim is to examine the impact of the original solvent based on substances for parenteral nutrition on biological systems exemplified by the hemostatic system, characterized by sensitivity and variability of the effects in response to any impact, and its comparison with the solvents that are conventional in pharmacological research. Experimental work is performed according to the "guidance on preclinical research of new pharmacological substances" in vitro. The findings show that traditional solvents at low dosages affect all the researched indicators of the hemostasis system. The smallest effect in respect of the hemostatic system was characterized by ethanol, and the most apparent antiaggregational effect was registered with dioxane. 10% concentration of original blend of lipids made no effect on hemostasis system. Thus, according to their own findings and experience in application of lipid emulsions as substances of parenteral nutrition, they can be considered to be an adequate solvent in all phases of preclinical and clinical studies of new drugs.