Shock-Associated Systemic Inflammation in Amniotic Fluid Embolism, Complicated by Clinical Death.

BACKGROUND: Amniotic fluid embolism (AFE) is one of the main causes of maternal mortality in developed countries. The most critical AFE variants may be considered from the perspective of systemic inflammation (SI), a general pathological process that includes high levels of systemic inflammatory response, neuroendocrine system distress, microthrombosis, and multiple organ dysfunction syndrome (MODS). This research work aimed to characterize the dynamics of super-acute SI using four clinical case studies of patients with critical AFE. METHODS: In all the cases, we examined blood coagulation parameters, plasma levels of cortisol, troponin I, myoglobin, C-reactive protein, IL-6, IL-8, IL-10, and TNF-α, and calculated the integral scores. RESULTS: All four patients revealed the characteristic signs of SI, including increased cytokine, myoglobin, and troponin I levels, changes in blood cortisol, and clinical manifestations of coagulopathy and MODS. At the same time, the cytokine plasma levels can be characterized not only as hypercytokinemia, and not even as a "cytokine storm", but rather as a "cytokine catastrophe" (an increase of thousands and tens of thousands of times in proinflammatory cytokine levels). AFE pathogenesis involves rapid transition from the hyperergic shock phase, with its high levels of a systemic inflammatory response over to the hypoergic shock phase, characterized by the mismatch between low systemic inflammatory response values and the patient's critical condition. In contrast to septic shock, in AFE there is a much more rapid succession of SI phases. CONCLUSION: AFE is one of the most compelling examples for studying the dynamics of super-acute SI.

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19.

The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus's protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2's ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation.

Chronic kidney disease can progress to end-stage chronic renal disease (ESRD), which requires the use of replacement therapy (dialysis or kidney transplant) in life-threatening conditions. In ESRD, irreversible changes in the kidneys are associated with systemic changes of proinflammatory nature and dysfunctions of internal organs, skeletal muscles, and integumentary tissues. The common components of ESRD pathogenesis, regardless of the initial nosology, are (1) local (in the kidneys) and systemic chronic low-grade inflammation (ChLGI) as a risk factor for diabetic kidney disease and its progression to ESRD, (2) inflammation of the classical type characteristic of primary and secondary autoimmune glomerulonephritis and infectious recurrent pyelonephritis, as well as immune reactions in kidney allograft rejection, and (3) chronic systemic inflammation (ChSI), pathogenetically characterized by latent microcirculatory disorders and manifestations of paracoagulation. The development of ChSI is closely associated with programmed hemodialysis in ESRD, as well as with the systemic autoimmune process. Consideration of ESRD pathogenesis from the standpoint of the theory of general pathological processes opens up the scope not only for particular but also for universal approaches to conducting pathogenetic therapies and diagnosing and predicting systemic complications in severe nephropathies.