Development Of Multiple Organ Dysfunction Research Articles

Biochemical Changes in Newborns with Intrauterine Hypoxia Born by Caesarean Section

The medical community is unswervingly joining forces to address issues of maternal and child health, which are acquiring political and social significance against the background of demographic problems of our time. At the heart of many conditions complicating the course of pregnancy and childbirth, there is a damaging factor that is universal for the fetus and newborn - hypoxia, which disrupts the course of basic energy-dependent processes, triggering a complex of pathological endogenous reactions that contribute to the development of multiple organ dysfunction.

Exosomal PGE2 from M2 macrophages inhibits neutrophil recruitment and NET formation through lipid mediator class switching in sepsis

BackgroundExcess polymorphonuclear neutrophil (PMN) recruitment or excessive neutrophil extracellular trap (NET) formation can lead to the development of multiple organ dysfunction during sepsis. M2 macrophage-derived exosomes (M2-Exos) have exhibited anti-inflammatory activities in some inflammatory diseases to mediate organ functional protection, but their role in treating sepsis-related acute lung injury (ALI) remains unclear. In this study, we sought to investigate whether M2-Exos could prevent potentially deleterious inflammatory effects during sepsis-related ALI by modulating abnormal PMN behaviours.MethodsC57BL/6 wild-type mice were subjected to a caecal ligation and puncture (CLP) mouse model to mimic sepsis in vivo, and M2-Exos were administered intraperitoneally 1 h after CLP. H&E staining, immunofluorescence and immunohistochemistry were conducted to investigate lung tissue injury, PMN infiltration and NET formation in the lung. We further demonstrated the role of M2-Exos on PMN function and explored the potential mechanisms through an in vitro coculture experiment using PMNs isolated from both healthy volunteers and septic patients.ResultsHere, we report that M2-Exos inhibited PMN migration and NET formation, alleviated lung injury and reduced mortality in a sepsis mouse model. In vitro, M2-Exos significantly decreased PMN migration and NET formation capacity, leading to lipid mediator class switching from proinflammatory leukotriene B4 (LTB4) to anti-inflammatory lipoxin A4 (LXA4) by upregulating 15-lipoxygenase (15-LO) expression in PMNs. Treatment with LXA4 receptor antagonist attenuated the effect of M2-Exos on PMNs and lung injury. Mechanistically, prostaglandin E2 (PGE2) enriched in M2-Exos was necessary to increase 15-LO expression in PMNs by functioning on the EP4 receptor, upregulate LXA4 production to downregulate chemokine (C-X-C motif) receptor 2 (CXCR2) and reactive oxygen species (ROS) expressions, and finally inhibit PMN function.ConclusionsOur findings reveal a previously unknown role of M2-Exos in regulating PMN migration and NET formation through lipid mediator class switching, thus highlighting the potential application of M2-Exos in controlling PMN-mediated tissue injury in patients with sepsis.

Predictive performance of multiple organ dysfunction in asphyxiated newborns treated with therapeutic hypothermia on 24-month outcome: a cohort study

BackgroundPerinatal asphyxia may be followed by multiple organ dysfunction (MOD) and is often included in prognostication of the individual patient, but evidence of discriminating accuracy is lacking. The aim of...

Some immunological biomarkers of the severity of neonatal sepsis in newborns depending on different inflammatory response

Background. Objective: to study the diagnostic value and indicators of clinical and epidemiological risk of some immunological biomarkers as indicators of the severity of the clinical course of neonatal sepsis in order to improve treatment outcomes in newborns with neonatal sepsis with an alternative serum content of C-reactive protein. Materials and methods. A comprehensive clinical and paraclinical examination of 56 children with neonatal sepsis was conducted. The severity of neonatal sepsis was determined using the constellation-diagnostic scales of multiple organ dysfunction such as SNAPII, SNAPРЕII, PELOD, SOFA, nSOFA, PEMOD, SCRIB, NEOMOD. The comprehensive immunological examination with evaluation of immunoglobulin A, G, M, C-reactive protein, presepsin, procalcitonin, interleukins (IL) 6, 8, 10 content in blood serum was conducted in all newborns. Two clinical groups were formed. The clinical group I included 25 infants with neonatal sepsis with a serum level of C-reactive protein < 20 mg/l (boys — 52.0 %, city residents — 80.0 %, the average content of C-reactive protein — 8.80 ± 0.41 mg/l). The clinical group II was formed by 31 children with neonatal sepsis and C-reactive protein blood concentration > 20 mg/l (with 62.8 % of boys, p > 0.05; 57.1 % of city residents, p > 0.05; the average content of C-reactive protein — 29.70 ± 1.89 mg/l, р < 0.05). According to the main clinical characteristics, the observation groups were comparable. Results. The conducted studies showed that the severity of the clinical course of neonatal sepsis, determined using the constellation-diagnostic scales of multiple organ dysfunction (SNAPII, SNAPРЕII, PELOD, SOFA, nSOFA, PEMOD, SCRIB, NEOMOD), did not reveal any significant differences in the comparison groups. It was found that in newborns with a C-reactive protein content < 20 mg/l, compared to representatives of the clinical group II, the concentration of IL-6, IL-8 and IL-10 was lower by 1.7, 1.5 and 1.8 times, respectively. Thus, patients of the group II had the risk of increasing serum content of IL-6 > 31.4 pg/ml (relative risk (RR) 1.7 (95% confidence interval (CI): 1.3–2.2) with an odds ratio (OR) 2.8 (95% CI: 1.6–5.1)), IL-10 > 18 pg/ml (RR 1.7 (95% CI: 1.1–2.4) with an OR 2.9 (95% CI: 1.6–5.3)), and IL-8 > 24.0 pg/ml (RR 1.9 (95% CI: 1.2–3.1) with an OR 4.7 (95% CI: 2.5–8.8)). Among the studied immunological biomarkers, the concentration of presepsin > 1,000 ng/ml was accompanied by the best indicators of the clinical and epidemiological risk of severe sepsis according to the constellation-diagnostic scales of multiple organ dysfunction (odds ratio 4.3–6.0, relative risk 2.3–2.5, attributable risk 32.0–42.0 %). Conclusions. Elevated content of some markers of neonatal sepsis (presepsin, procalcitonin) and interleukins (IL-6, IL-8) can be considered a biomarker of a severe course of neonatal sepsis with probable development of multiple organ dysfunction.

Biomarker-based risk model to predict persistent multiple organ dysfunctions after congenital heart surgery: a prospective observational cohort study

BackgroundMultiple organ dysfunction syndrome (MODS) is an important cause of post-operative morbidity and mortality for children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). Dysregulated inflammation is widely regarded as a key contributor to bypass-related MODS pathobiology, with considerable overlap of pathways associated with septic shock. The pediatric sepsis biomarker risk model (PERSEVERE) is comprised of seven protein biomarkers of inflammation and reliably predicts baseline risk of mortality and organ dysfunction among critically ill children with septic shock. We aimed to determine if PERSEVERE biomarkers and clinical data could be combined to derive a new model to assess the risk of persistent CPB-related MODS in the early post-operative period.MethodsThis study included 306 patients < 18 years old admitted to a pediatric cardiac ICU after surgery requiring cardiopulmonary bypass (CPB) for congenital heart disease. Persistent MODS, defined as dysfunction of two or more organ systems on postoperative day 5, was the primary outcome. PERSEVERE biomarkers were collected 4 and 12 h after CPB. Classification and regression tree methodology were used to derive a model to assess the risk of persistent MODS.ResultsThe optimal model containing interleukin-8 (IL-8), chemokine ligand 3 (CCL3), and age as predictor variables had an area under the receiver operating characteristic curve (AUROC) of 0.86 (0.81–0.91) for differentiating those with or without persistent MODS and a negative predictive value of 99% (95–100). Ten-fold cross-validation of the model yielded a corrected AUROC of 0.75 (0.68–0.84).ConclusionsWe present a novel risk prediction model to assess the risk for development of multiple organ dysfunction after pediatric cardiac surgery requiring CPB. Pending prospective validation, our model may facilitate identification of a high-risk cohort to direct interventions and studies aimed at improving outcomes via mitigation of post-operative organ dysfunction.

LETHALITY ANALYSIS IN PATIENTS WITH ACUTE SMALL BOWEL OBSTRUCTION. ADVERSE FACTORS AND POSSIBLE WAYS TO ELIMINATE THEM

The aim: To determine obstruction factors that can lead to lethal consequences for patients with acute small intestine in order to develop possible directions for their prevention. Materials and methods: During the retrospective analysis of 30 patients with acute small bowel obstruction, the causes and contributing factors of mortality were determined. Results: The cause of mortality in the $rst three days of the postoperative period was the progression of the phenomena of intoxication, which led to the appearance of the syndrome of enteric insu%ciency and the development of multiple organ dysfunction. Mortality in the later period was observed due to the decompensation of concomitant diseases that accompanied acute obstruction of the small intestine. In the process of the study it was determined that the possible reasons of the postoperative complications in the studied group of patients, apart from the elderly and senile age of the patients and delayed medical care, according to the results of our observation were: uncorrected hypotension and hypovolemia in the postoperative period, refusal of the intubation of the small intestine and permanent decompression of the gastrointestinal tract, early removal of the nasogastric tube, long-term anemia and hypoproteinemia, prevention of stress ulcers of the gastrointestinal tract in the elderly and senile age, refusal of early use of enteral nutrition and later restoration of motility of the gastrointestinal tract. Conclusions: Treatment of patients with acute small intestine obstruction requires the selection of a specially designed treatment program (optimal timing of preoperative preparation, selection of the minimum volume) at all stages of surgical care, taking into account the existing concomitant pathology, age and hospitalization period.

Molecular Mechanisms Underlying Intensive Care Unit-Acquired Weakness and Sarcopenia.

Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect—sarcopenia—the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism—mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.

ОСТРЫЙ ГНОЙНЫЙ ПИЕЛОНЕФРИТ ЕДИНСТВЕННОЙ ПОЧКИ

Background. One of the life-threatening diseases among patients with a single kidney is acute purulent pyelonephritis (APP). The disease is accompanied by oliguria or anuria and in many cases comes with the development of multiple organ dysfunction. Objectives. To present the features of the clinical manifestations of APP of a solitary kidney, the results of clinical and laboratory examination, the role of kidney imaging methods (USG, MRI and contrast-enhanced CT) in identifying foci of purulent destruction in the parenchyma, and the immediate results of treatment of patients with APP of a solitary kidney. Material and methods. 10 patients with APP of a solitary kidney were observed. The role of imaging methods (USG, CT and MRI) of the kidney in the detection of purulent destruction in parenchyma is shown. Methods of treating patients are considered: open organ-preserving surgery, nephrectomy; installation of an internal ureteral stent followed by antibiotic therapy and puncture nephrostomy followed by antibiotic therapy. Results. The best immediate results were noted in the group of patients who underwent open organ-preserving surgery in the volume of decapsulation of the kidney, excision of carbuncles, opening of abscesses and drainage of the calices-pelvis system of the kidney with nephrostomy. 3 out of 10 patients needed hemodialysis. Conclusion. Open organ-preserving surgery remains a reliable adequate method of surgical treatment of APP of a solitary kidney. In case of a single focus of destruction in the kidney parenchyma up to 3 cm in diameter or with signs of apostematous pyelonephritis, an effective method of treatment is the installation of an internal ureteral stent followed by antibiotic therapy. 30% of patients with APP need hemodialysis treatment.

Position statement on the use of albumin in liver cirrhosis

Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.

Incidence, Outcomes and Predictors of Early Postoperative Vasoplegia in Lung Transplantation: Experience from a 6-Year Period

<h3>Purpose</h3> Postoperative complications contribute to graft dysfunction, non-pulmonary morbidity, increased mortality and a ripple effect on long-term outcomes. We hypothesized vasoplegia plays a central role in postoperative adverse events and development of multiple organ dysfunction. <h3>Methods</h3> Perioperative data of 279 lung transplant (LTx) recipients operated between 2015-2020 was retrospectively curated by our institutional Informatics Team using a Clinical Data Warehouse. Vasoplegia was defined according to Tsiouris et al., and acute kidney injury (AKI) to KDIGO criteria. <h3>Results</h3> Vasoplegia affected 116 (41.6%) patients with 36 (31.0%) having mild, 64 (55.2%) moderate, and 16 (13.8%) severe vasoplegia. Vasoplegia was associated with higher incidence of any AKI (78.5% vs 65%, <i>p</i> 0.015) and vasoplegic patients were more likely to develop AKI stage III (52.6%) when compared to AKI stage I (16.4%, <i>p</i> 0.036) or no AKI (21.5%, <i>p</i> < 0.001). The need for renal replacement therapy doubled (47.4% vs 24.5%, <i>p</i> < 0.001) in the vasoplegic group. Vasoplegic patients had higher incidence of delayed chest closure (18.4% vs 9.2%, <i>p</i> 0.025), needed longer ventilation duration (70 [32-368] vs 34 [19-105] hours, <i>p</i> < 0.001) and increased ICU length of stay (12.9 [5-30] vs 6.8 [3-20] days, <i>p</i> < 0.001). Their 30-day mortality was 11.2% compared to 5.5% in patients with no vasoplegia (<i>p</i> 0.082). One-year mortality was also increased (20.7% vs 11.7%, <i>p</i> 0.039) and severe vasoplegia represented a hazard (HR 2.60, 95% CI 1.14-5.94, <i>p</i> 0.023) for long-term survival (<i>p</i> 0.037). Vasoplegic patients showed increased inflammatory markers at 72 hours, including white blood cells (<i>p</i> 0.037), neutrophils (<i>p</i> 0.042) and C-reactive protein (CRP, <i>p</i> 0.010). Multivariate regression analysis identified preoperative bilirubin as a predictor of vasoplegia (<i>p</i> 0.008). Underlying infectious lung disease (<i>p</i> 0.041), preoperative pulmonary artery systolic pressure (<i>p</i> 0.036), pre-LTx glomerular filtration rate (<i>p</i> 0.035) and CRP (<i>p</i> 0.040) were identified as predictors of vasoplegia severity. <h3>Conclusion</h3> Vasoplegia is a common and critical condition after LTx in its entire spectrum. It has a tremendous impact on perioperative and longer-term clinical outcomes. Preoperative status as well as procedural factors and inflammatory response are major determinants of vasoplegia.

The Successful Use of Combined Extracorporeal Life Support in Treatment of the New Coronavirus Infection Complicated by the Development of Multiple Organ Dysfunction in a Pregnant Woman

Pregnant and postpartum women are at a higher risk of infection with SARS-CoV-2 as well as a higher risk of adverse outcomes for the mother and fetus. Standard approaches to the management of COVID-19-associated multiple organ dysfunction may not always be implemented in this category of patients. In the clinical case of a patient, who developed multiple organ dysfunction syndrome (severe ARDS, coagulopathy) associated with COVID-19 in the postpartum period, we demonstrate the successful use of combined extracorporeal life support that included veno-venous extracorporeal membrane oxygenation, therapeutic plasma exchange and renal replacement therapy with the universal oXiris set.

Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction

BackgroundTo date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD.MethodsThe clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD.ResultsThe ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time.ConclusionsThe cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.

Anticoagulation therapy using unfractionated heparin at a therapeutic dose for coronavirus disease 2019 patients with severe pneumonia: a retrospective historical control study.

AimPatients with severe coronavirus disease 2019 (COVID‐19) pneumonia often have complications of coagulopathy and thrombotic phenomena, which lead to high mortality. Whether administering systematic anticoagulant therapy is beneficial remains unclear. We report our experience using systemic anticoagulation with unfractionated heparin to treat severe COVID‐19.MethodsWe conducted a retrospective historical control study of severe COVID‐19 patients requiring mechanical ventilation who received prophylactic‐dose anticoagulation (April 1–May 25) or therapeutic‐dose anticoagulation (May 26–August 31) in the intensive care unit (ICU) of a tertiary emergency critical care medical center in Japan. The primary endpoints were in‐hospital mortality and anticoagulation therapy‐related adverse events. The secondary endpoints included thromboembolic events, administration of venovenous extracorporeal membrane oxygenation (ECMO), ventilator‐free days (VFDs), ICU‐free days, and the development of multiple organ dysfunction syndrome.ResultsA total of 29 and 33 patients were in the prophylactic‐dose and therapeutic‐dose groups, respectively. Background characteristics between the groups were not significantly different, although the therapeutic‐dose group had a significantly lower in‐hospital mortality rate [5 (17.2%) patients versus 0 (0.0%) patients; P = 0.033] and longer ICU‐free days (median [interquartile range]: 15 days [13–18] versus 5 days [0–13]; P = 0.008). Hemorrhagic‐events did not occur during the study period. Compared with the prophylactic‐dose group, the therapeutic‐dose group tended to have longer VFDs, was not treated with ECMO, and did not experience thromboembolic events and multiple organ dysfunction syndrome; however, the difference was not statistically significant.ConclusionsTherapeutic‐dose anticoagulation may be beneficial for patients with severe COVID‐19 pneumonia requiring mechanical ventilation.

PECULIARITIES OF BILIARY FUNCTION OF THE LIVER IN THE DYNAMICS OF POLYTRAUMA IN THE EXPERIMENT

Relevance. Severe trauma is accompanied by the development of multiple organ dysfunction and the insufficiency of internal organs. The dynamics of changes in the functional state of the liver didn't investigate fully. It is the central organ of detoxification of the body, whose activity occurs in close integration with other organs and systems of the body.&#x0D; The objective is to find out the features of the biliary function of the liver in the dynamics of the developed model of polytrauma.&#x0D; Materials and methods. Polytrauma was performed using 62 nonlinear white male rats weighing 180-200 g under conditions of thiopental-sodium anesthesia (40 mg 1kg-1 intraperitoneally). In surviving animals, the biliary function of the liver was studied in 2 h, 1, 3, 7, 14, 21, and 28 days after injury. For this purpose, the common bile duct was catheterized, and bile was collected for 1 hour in animals under thiopental-sodium anesthesia (60 mg kg-1). The rate of bile excretion and the concentration of total bile acids, cholesterol, direct and indirect bilirubin in the selected portion of bile were determined. Based on these data, the rate of excretion of the studied components of bile was calculated. Euthanasia of rats throughout the experiment was performed by total bloodletting from the heart after previous thiopental-sodium anesthesia (60 mg kg-1 intraperitoneally). The obtained digital data were subject to statistical analysis.&#x0D; Results. In the conditions of experimental polytrauma, there is a violation of the biliary function of the liver. It is manifested in the period of an acute reaction to the trauma first (after 2 hours) by a significant it decreases, then (up to 1 day) development of polycholia - 1.52 times increased of bile secretion. Also increased excretion of the main components of bile, with their subsequent decrease to 7 days, development of the period of temporary improvement in 14 days with the repeated of exacerbation period in 21 days and approach to the norm - in 28 days.&#x0D; The decrease in bile secretion corresponds to a period of shock, which is characterized by the centralization of blood circulation and reduced blood supply to the organs of the gastrointestinal tract. Increased bile secretion and excretion of main bile components in 1 day after a severe injury is associated with the increased biliary polarity of hepatocytes and unloading of the liver from endotoxins. It accumulates due to tissue damage, microcirculation, and hypoxia. Subsequently, the indicators of the biliary function of the liver changed by the identified patterns of lipoperoxidation deviations, antioxidant protection, cytolysis, and endogenous intoxication. The pathogenesis of biliary disorders is the damage of the endoplasmic reticulum membranes, where the synthesis of the main components of bile. As well as the development of edema of the organ, which prevents the outflow of bile.&#x0D; Conclusion. The dynamics of the development of functional liver failure due to polytrauma coincides with the general pattern characteristic of the dynamics of other biochemical markers of traumatic disease. Namely: after 3 days of the post-traumatic period, there was a phase of maximum deepening of deviations of the studied indexes. After 7-14 days there was noted a phase of temporary improvement which is characterized by a change of indexes towards the norm. After 21 days there was a re-exacerbation of the pathological process. After 28 days the indexes changed towards the norm, but for most cases do not reach it.&#x0D; This means that in a critical state of the body the organs and systems coupling is getting worse, which are remote from the site of injury. It can be considered as a factor of compensation and adaptation directed to the survival of the organism.

Morphological rearrangement of large joints of the lower extremities under the conditions of a combination of abdominal and orthopedic trauma complicated by ischemia-reperfusion of the extremity

Introduction. Injuries are among the pressing problems of modern urban society. The structure of injuries is dominated by multiple and combined injuries, which are characterized by significant severity and high mortality and lead to multiple organ dysfunction and insufficiency. In recent years, studies of the functional state of the liver have been widely used as a model for the development of multiple organ dysfunction in conditions of severe experimental trauma.The objective is to determine the nature of disorders of biliary function of the liver in conditions of combined trauma to the abdomen and chest of rats in the early period of traumatic disease and to evaluate the effectiveness of their correction with thiotriazoline.Research materials and their discussion. The experiments were performed on 86 nonlinear white male rats weighing 200-220 g. All animals were divided into five groups i.e. one control group and four experimental ones. Injuries were performed under thiopental-sodium anesthesia. The control group included intact animals that had just been anesthetized. In the first experimental group, the animals were simulated chest trauma. In the second experimental group, a blunt trauma was simulated. In the third experimental group, these injuries were combined. In the fourth experimental group, animals with combined trauma were injected intraperitoneally with thiotriazoline at a dose of 9.1 mg-kg-1. 1, 3 and 7 days after injury under thiopentalone sodium anesthesia in animals, the common bile duct was catheterized and bile was collected for 60 min. It was set the rate of bile excretion. The concentration of total bile acids and conjugated bilirubin was determined in bile, and the rate of their excretion was calculated.Research results and their discussion. Under conditions of isolated trauma of the chest, abdomen and their combination, there is a significant violation of biliary function of the liver, which is primarily manifested by a decrease in the rate of bile secretion and excretion of its main components - cholates and conjugated bilirubin. According to the severity of hepatic dysfunction, they can be divided as follows: isolated chest injury ← isolated abdominal injury ← combined injury. Under conditions of isolated chest trauma, the studied parameters in comparison with the control reach a minimum level of up to 3 days and normalize up to 7 days. After applying an isolated abdominal injury, the rate of bile secretion and the rate of excretion of total bile acids are reduced after 1 day. However, all the studied indicators reach a minimum value after 3 days and remain at the same level until 7 days. After a combined injury, the rates gradually decrease to 7 days and in each subsequent period become significantly lower than in the previous one. The use for the correction of detected disorders of thiotriazoline in the group of animals with combined trauma compared with animals without correction contributed to a significant increase in the rate of bile excretion, excretion of total bile acids and conjugated bilirubin. Although up to 7 days the indicators did not reach the level of the control group, it can be argued that thiotriazoline has a positive effect on biliary function of the liver.Conclusion. Combined trauma to the abdomen and chest contributes to a greater decrease in liver function, compared with isolated lesions. They are based on the suppression of the rate of bile secretion and excretion of total bile acids and conjugated bilirubin. The use of thiotriazoline at a dose of 9.1 mgkg-1 in animals with combined abdominal trauma is accompanied by a significant decrease in biliary dysfunction.

Acute Lung Injury: Disease Modelling and the Therapeutic Potential of Stem Cells.

Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality that usually results in the development of multiple organ dysfunction. The complex pathophysiology of ALI seems to provide a wide range of targets that offer numerous therapeutic options. However, despite extensive studies of ALI pathophysiology and treatment, no effective pharmacotherapy is available. Increasing evidence from both preclinical and clinical studies supports the preventive and therapeutic effects of mesenchymal stem cells (MSCs) for treating ALI. As cell-based therapy poses the risk of occlusion in microvasculature or unregulated growth, MSC-derived extracellular vesicles (MSC-EVs) have been extensively studied as a new therapeutic strategy for non-cell based therapy. It is widely accepted that the therapeutic properties of MSCs are derived from soluble factors with paracrine or endocrine effects, and EVs are among the most important paracrine or endocrine vehicles that can deliver various soluble factors with a similar phenotype as the parent cell. Therapeutic effects of MSCs have been reported for various delivery approaches, diverse doses, multiple origins, and different times of administration, and MSC-EVs treatment may include but is not limited to these choices. The mechanisms by which MSCs and MSC-EVs may contribute to ALI treatment remain elusive and need further exploration. This review provides an overview of preclinical studies that support the application of MSC-EVs for treating ALI, and it discusses emerging opportunities and their associated challenges.

Cardiogenic shock: an update

Cardiogenic shock is a critical condition characterized by rapid development of multiple organ dysfunction in the absence of intensive care. The article describes Abstract modern concepts about pathophysiology and approaches to treat intensive care. The concept of phased therapy as well as methods of mechanical circulatory support are discussed. The working algorithm for choosing the optimal method was proposed.

The Prognostic Value of Endotoxemia and Intestinal Barrier Biomarker ZO-1 in Bacteremic Sepsis

BackgroundIntestinal barrier dysfunction exerts a pivotal pathophysiological role in the development of multiple organ dysfunction in sepsis. The present study was undertaken to investigate the potential role of serum intestinal fatty acid-binding protein (I-FABP) and zonula occludens-1 (ZO-1) levels as biomarkers of intestinal barrier dysfunction in bacteremic sepsis. MethodsSeventy-five patients with bacteremic sepsis of abdominal origin (n = 34) or nonabdominal origin (n = 41) and 12 healthy controls were retrospectively studied. Blood samples collected upon sepsis diagnosis were analyzed for serum ZO-1, I-FABP and endotoxin levels. Prognostic scores Sequential Organ Failure Assessment (SOFA), quickSOFA and Acute Physiology and Chronic Health Evaluation (APACHE-II) were determined over the first 24 hours after sepsis diagnosis and patients’ outcome in terms of 28-day mortality was recorded. ResultsSerum ZO-1 levels were significantly higher in bacteremic septic patients as compared to controls with no difference between patients with abdominal or extra-abdominal source of infection. Serum I-FABP levels were significantly lower in septic patients as compared to control and this reduction was more evident in patients with bacteremic abdominal sepsis. Serum ZO-1 and endotoxin concentrations were found significantly higher in patients who did not survive from sepsis. In receiver operating characteristic curve analysis, both endotoxin and ZO-1 predicted 28-day mortality. In addition, ZO-1 and endotoxin were correlated with the prognostic scores of qSOFA, SOFA and APACHE II. ConclusionsThe results of this study indicate that serum ZO-1 might be a reliable biomarker of gut barrier dysfunction in sepsis, not affected by the abdominal or extra-abdominal site of infection. ZO-1, measured early at sepsis diagnosis, might represent a valuable additional prognostic tool for patients’ outcome.

The Number and Potency of Endothelial Progenitor Cells in Type 2 Diabetes Mellitus Patients

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a metabolic disease, due to the disorder of insulin function, insulin secretion, or both. Long-term hyperglycemia conditions promote endothelial dysfunction precedes to the development of multiple organ dysfunctions. Endothelial progenitor cells (EPCs) and hematopoietic stem cell (HSCs) are the key cellular effectors of postnatal neovascularization and play central role in endothelial dysfunction. However, in T2DM condition, the number of apoptotic HSCs increase, it may cause the reduction in potency and number of EPCs. In diabetes, the circulating EPCs number decrease and their functionality is impaired, but mechanism underlie of this impairement is unknown. The purpose of this study was to examine the relationship duration diabetes with the number and potency of EPC cells in T2DM patients controlled and poorly controlled.METHODS: Thirty-eight T2DM male patients were classified into two group based on Indonesian Society of Endocrinology/Perkumpulan Endokrinologi Indonesia (PERKENI) criteria on T2DM. The first group was a controlled glycemic condition group (hemoglobin A1c (HbA1C) &lt;7.0%) and the second group was a poorly controlled glycemic condition group (HbA1C &gt;7.0%). Cluster of differentiation (CD)34+ and CD133+ expressions were used as specific marker for EPC, while quantified bright aldehyde dehydrogenase (ALDHbr) assay was used to represented the potency of EPCs.RESULTS: This study showed that in poorly controlled T2DM group the number of EPCs was lower by 24.80% (p&lt;0.05) compared to the T2DM controlled group. Similarly, the expression of ALDHbr was lower by 43.07% (p&lt;0.05) in poorly controlled group.CONCLUSION: There was a decrease in the number and potency of EPCs in poorly controlled T2DM patients compared to the controlled T2DM patients. There was also a strong negative correlation between the duration of diabetes and number of EPCs.KEYWORDS: ALDHbr, endothelial progenitor cells, type 2 diabetes mellitus

РАСТВОР АЛЬБУМИНА В СОВРЕМЕННОЙ КОНЦЕПЦИИ ИНФУЗИОННОЙ ТЕРАПИИ – ИСТОРИЯ ПРОДОЛЖАЕТСЯ?

Hypoalbuminemia and hypovolemia are independent risk factors for the development of multiple organ dysfunction, the main cause of death in critically ill patients. The use of a human albumin (HA) solution in complex of the fluid therapy affects both of these risk factors. However, more than 75 years of experience of HA use by the medical community and numerous clinical studies have proved its safety but did not lead to a consensus on the clinical effectiveness of its use. Thus, questions remain, and in which patients the use of HA is most appropriate. The authors of this review attempted to summarize the knowledge accumulated by the medical community on the use of HA in the practice of intensive care.