Inflammation-Induced Coagulopathy Substantially Differs Between COVID-19 and Septic Shock: A Prospective Observational Study

Critical COVID-19, like septic shock, is related to a dysregulated systemic inflammatory reaction and is associated with a high incidence of thrombosis and microthrombosis. Improving the understanding of the underlying pathophysiology of critical COVID-19 could help in finding new therapeutic targets already explored in the treatment of septic shock. The current study prospectively compared 48 patients with septic shock and 22 patients with critical COVID-19 regarding their clinical characteristics and outcomes, as well as key plasmatic soluble biomarkers of inflammation, coagulation, endothelial activation, platelet activation, and NETosis. Forty-eight patients with matched age, gender, and co-morbidities were used as controls. Critical COVID-19 patients exhibited less organ failure but a prolonged ICU length-of-stay due to a prolonged respiratory failure. Inflammatory reaction of critical COVID-19 was distinguished by very high levels of interleukin (IL)-1β and T lymphocyte activation (including IL-7 and CD40L), whereas septic shock displays higher levels of IL-6, IL-8, and a more significant elevation of myeloid response biomarkers, including Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) and IL-1ra. Subsequent inflammation-induced coagulopathy of COVID-19 also differed from sepsis-induced coagulopathy (SIC) and was characterized by a marked increase in soluble tissue factor (TF) but less platelets, antithrombin, and fibrinogen consumption, and less fibrinolysis alteration. In conclusion, COVID-19 inflammation-induced coagulopathy substantially differs from SIC. Modulating TF release and activity should be evaluated in critical COVID-19 patients.

Clinical importance of determination of procalcitonin in diagnosis of sepsis

The review presents an assessment of the dynamics of the change in procalcitonin as the main marker of bacterial inflammation in patients with the syndrome of systemic inflammatory reaction, sepsis and septic shock, clarification of the practical and predictive significance of PCT in patients with an identified and not identified focus of infection.

ON THE ISSUE OF DIFFERENTIAL DIAGNOSIS OF BACTERIAL INFECTIONS AND PEDIATRIC MULTISYSTEM INFLAMMATORY SYNDROME DURING THE COVID-19 PANDEMIC

During the COVID-19 pandemic, it is necessary to be wary of the development of pediatric multisystem inflammatory syndrome in children (PMIS) who have had a COVID-19 and had antibodies to the SARS-CoV-2 virus. The aim of this work is to describe two clinical cases in children with antibodies to SARS-CoV-2 against the background of yersiniosis in a 12-year-old child and salmonellosis in a 3-year-old child, which proceeded with a pronounced inflammatory reaction and required a differential diagnosis with multisystem inflammatory syndrome. These bacterial infections proceeded with severe intoxication and fever, had a polymorphic clinical picture with exanthema syndrome, conjunctivitis/scleritis, swelling of the palms/feet, diarrhea and toxic kidney damage, with a pronounced systemic inflammatory reaction – high leukocytosis with neutrophilia and lymphopenia, a significant increase in C-reactive protein, procalcitonin, hypercoagulability (increased fibrinogen, D-dimer). Etiotropic antibiotic therapy led to recovery in both cases. Conclusions: During the COVID-19 pandemic, if antibodies to the SARS-CoV-2 virus are detected in children in the presence of signs of systemic inflammation and corresponding symptoms, the alertness of doctors and a timely comprehensive examination are necessary to exclude bacterial infections, also characterized by signs of systemic inflammation, for the purpose of differential diagnosis of PMIS.

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of “bacteria, poison and inflammation” and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

High cytokine levels and cytokine storm in the novel coronavirus infection

A review article is based on current foreign sources. The level of cytokines in the peripheral blood can be increased in many diseases, but in some cases there may be an excess of their normal concentration in tens, hundreds or more times with the development of a peculiar clinical picture, which is based on a systemic inflammatory reaction. In the literature this condition has received the figurative name «cytokine storm», which highlights an extremely violent reaction of the immune system with an unknown (often unfavorable) outcome. Close attention of the scientific world and the public to the problem of extremely high levels of cytokines in the peripheral blood (hypercytokinemia) was drawn due to the high frequency of the cytokine storm in the novel coronavirus infection.

Clinical case of fatal panniculitis resulting from administration of lipolytic

The article describes a clinical case of a five-fold administration of a direct lipolytic–phosphatidylcholine / deoxycholic acid for cosmetic purposes, which resulted in widespread septal panniculitis, systemic inflammatory reaction, secondary myositis, thrombotic microangiopathic syndrome, fatty necrosis of the pancreatic head, necrotic nephrosis and multiple organ failure, which led to death of the patient.Materials and methods. Analysis of medical records, histological examination of autopsy material.Conclusions. Injection lipolysis using phosphatidylcholine / deoxycholate causes uncontrolled necrosis of adipose and vascular tissue, fibrosis, which makes the indefinitely long-term consequences of the administration of drugs for the non-surgical treatment of subcutaneous fat deposits. Phosphatidylcholine / sodium deoxycholate is not recommended for use in the presence of general obesity, somatic pathology, or in elderly patients.

Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?

Background: Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. Methods In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines. Results: CRS occurred at a median of 20 hours (range 8–27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13–33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported ( p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1–2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5. Conclusion: Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS.

Combined therapy with Medotilin/Elfunat for the prevention and treatment of neuropsychiatric complications after open-heart surgery

After open-heart surgery, postoperative neuropsychiatric complications often develop: stroke — in 4.8 % of cases, diffuse encephalopathy — in 12 %, behavior changes — in 5–40 %, cognitive impairment — in 12–79 %, mental disorders — in 13–64 %. The causes of their development are acetylcholine deficiency with subsequent dysfunction of the cholinergic system and oxidative stress, which result from hypoxia, hypoperfusion, and a systemic inflammatory reaction. In this regard, the appointment of drugs that restore the acetylcholine synthesis – choline alfoscerate (Medotilin), and drugs that suppress oxidative stress – mexidol (Elfunate) is considered a promising direction for the prevention and treatment of neuropsychiatric complications. The study conducted on the basis of the regional cardiac surgery center of the Odessa Regional Hospital demonstrated that the combined use of Medotilin and Elfunate can reduce the frequency of neuropsychiatric complications, as well as reduce the duration of treatment in the hospital.

EP.WE.629The effect of different anaesthetic agents in postsurgical inflammatory response in thoracic surgery: a systematic review

Aims Post-operative systemic inflammatory reaction is part of the stress response caused by major thoracic surgery. Different anaesthetic agents used affect different immunological phenomena. This systematic review evaluates the impact of anaesthetic agents on the immunological profile and the associated clinical significance. Methods A systematic review of MEDLINE, EMBASE and Cohrane databases to explore how different anaesthetic agents affect post-operative inflammatory response. Results A total of nine studies were included in our analysis. Peri-operative use of dexmedetomidine, propofol, sevoflurane, isoflurane, ropivacaine, sufentanil, naloxone and clonidine were compared, based on their effect on the systemic release of inflammatory markers. Variance on the levels of the circulating inflammatory molecules such as interleukins, interferon-γ, tumor necrosis factor a and on the cellular response including natural killer, CD4 and CD8 T cells, were observed among different anaesthetic agents. Conclusions Inflammation improves immunity and regenerative cell recruitment, however excessive responses can lead to delayed wound healing, organ dysfunction and increased morbidity and mortality. There is still uncertainty regarding the role of immune changes on clinical outcomes of patients undergoing thoracic surgery, and more research is needed to explore other immunological effects related to anaesthetic agents.

Evaluation of the effectiveness of negative pressure wound therapy in the complex treatment of patients with infected mesh endoprostheses of the anterior abdominal wall

Introduction. Wound complications after the placing of various implants of the abdominal wall after hernia repair account for up to 15 % of all hospitalizations with purulent diseases. Their treatment is often accompanied by a high frequency of explantation of a mesh endoprosthesis with a risk of recurrent hernias in this category of patients.The objective of the study was to improve the results of surgical treatment of patients with infected implants of the abdominal wall after herniaplasty based on the assessment of the effectiveness of the negative pressure wound therapy (NPWT).Methods and materials. A retrospective analysis of the treatment results of patients with infected mesh endoprostheses of the anterior abdominal wall (n=68) was carried out. We formed for comparison two homogeneous representative groups of patients, who underwent adequate debridement of a purulent wound with empirical antibiotic therapy. Patients from the study group (n=38) received local therapy using NPWT, patients from the control group (n=30) received traditional local therapy. The evaluation of the treatment results was carried out according to a number of criteria: the course of the systemic inflammatory reaction, the dynamics of reparative processes in the wound of the anterior abdominal wall, evaluation of the clinical outcomes of treatment of patients.Results. The use of vacuum therapy was accompanied by a positive effect on the course of the systemic inflammatory reaction, stimulation of reparative processes in the wound due to the rapid elimination of bacterial agents from the wound cavity (p= 0.003), as well as significant retraction of the wound cavity (p=0.004) compared to traditional methods of wound treatment. Patients from the study group had more favorable treatment outcomes such as a reduction in the duration of hospitalization (p=0.005) and the number of surgical interventions (p=0.003). Due to the NPWT, it was possible to save implants in 30 patients out of 38 (78.9%) with infected mesh endoprostheses of the anterior abdominal wall, which prevented the formation of recurrent hernias and helped to avoid reoperations in this category of patients.Conclusion. The use NPWT is a safe and effective method for treating wounds of the anterior abdominal wall with infected mesh endoprostheses after hernioplasty.