The Relationship between Nrf2 and HO-1 with the Severity of COVID-19 Disease.

Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) have significant roles in the development of a hyperinflammatory state in infectious diseases. We aimed to investigate the association of the serum concentrations of Nrf2 and HO-1 with the severity of COVID-19 disease. The study included 40 subjects with mild and moderately severe forms of the disease (MEWS scoring system ≤2). Twenty of the subjects had MEWS scores of 3 or 4, which indicate a severe form of the disease, and twenty subjects had a MEWS score of ≥5, which indicates a critical form of the disease. HO-1 and Nrf2 were measured using the commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Subjects with the most severe form of COVID-19 (critically ill) had a lower concentration of Nrf2 that negatively correlated with the markers of hyperinflammatory response (CRP, IL-6, ferritin). This observation was not made for HO-1, and the correlation between Nrf2 and HO-1 values was not established. In the mild/moderate form of COVID-19 disease, Nrf2 was associated with an increased 1,25 dihydroxy vitamin D concentration. The results of this study show that Nrf2 has a role in the body's anti-inflammatory response to COVID-19 disease, which makes it a potential therapeutic target.

Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications.

Background: One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years; however, little is known about its role in sepsis in humans. This study aimed to assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality, invasive mechanical ventilation (IMV) requirement, and length of stay (LOS) in patients with sepsis. Materials and Methods: In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, N=53; nonsurvival, N=53), IMV requirement (IMV group, N=26; non-IMV group, N=80), and LOS (LOS <10 days, N=59; LOS ≥10 days, N=47). Patients' clinical status was assessed along with laboratory biomarkers as well as AEA and 2-AG concentration measurements early on admission to emergency units. AEA and 2-AG levels were measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA processor, EtiMax 3000 (DiaSorin, Saluggia, Italy). The predictive value of AEA and 2-AG for the studied sepsis outcomes and complications was analyzed using univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis. Results: Two endocannabinoids showed no significant difference between survivors and nonsurvivors, although an AEA concentration <7.16 µg/L predicted mortality outcome with a sensitivity of 57% (95% confidence interval [CI] 42-71) and specificity of 80% (95% CI 66-91). AEA concentrations ≤17.84 µg/L predicted LOS ≥10 days with sensitivity of 98% (95% CI 89-100) and specificity of 34% (95% CI 22-47). When analyzing IMV requirement, levels of AEA and 2-AG were significantly lower within the IMV group compared with the non-IMV group (5.94 µg/L [2.04-9.44] and 6.70 µg/L [3.50-27.04], p=0.043, and 5.68 µg/L [2.30-8.60] and 9.58 µg/L [4.83-40.05], p=0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% (p<0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03-183.83; p=0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67-0.93; p=0.004). Conclusion: Low AEA concentration is a prognostic factor of hospital LOS longer than 10 days. Lower AEA and 2-AG concentrations obtained at the time of admission to the hospital are predictors of IMV requirement.

The Correlation of Serum Calpain 1 Activity and Concentrations of Interleukin 33 in COVID-19 Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is one of the most severe complications of the COVID-19 disease. The role of IL-33 and calpain 1 was previously described in lung infections and lung tissue damage. Our study examined the association between serum calpain 1 activity and IL-33 concentration in patients with COVID-19 ARDS. In the research, we included 80 subjects who had COVID-19 pneumonia and divided them into 2 groups: 40 subjects with ARDS and 40 subjects without ARDS. The basis of the research was the collection of subjects' data and the sampling of peripheral venous blood. The concentration of IL-33 was determined by the ELISA method and the activity of calpain 1 by the fluorometry method. Our research showed elevated calpain 1 activity and IL-33 concentration in the serum of COVID-19 patients who developed ARDS compared to those who did not develop ARDS and a positive correlation between them was established. Further, a positive correlation was established between the examined parameters and the severity of the disease, proinflammatory markers, and the use of mechanical ventilation. These results indicate a possible association and role of calpain 1 and IL-33 with the development of ARDS in COVID-19 patients.

The Role of Extracorporeal Blood Purification in the Treatment of a Patient with Lemierre's Syndrome.

Lemierre's syndrome refers to the septic thrombophlebitis of the internal jugular vein. The condition typically begins with an oropharyngeal infection and frequently involves inflammation within the wall of the vein, infected thrombus within the lumen, surrounding soft tissue inflammation, persistent bacteremia, and septic emboli. Lemierre's syndrome is a rare disease; it occurs most commonly in otherwise healthy young adults. The most common etiologic agent is Fusobacterium necrophorum. We present a case of Lemierre's syndrome in a young girl and the role of extracorporeal method of blood purification with continuous venous hemodiafiltration with the use of a highly adsorptive membrane (AN69 HeprAN), thus achieving the combined elimination of cytokines and endotoxins. The use of advanced methods, along with an antibiotic and surgical treatment, will certainly help reduce mortality in this syndrome.

Right Heart Morphology and Its Association With Excessive and Deficient Cardiac Visceral Adipose Tissue.

Visceral adipose tissue is an independent risk factor for the development of atherosclerotic coronary disease, arterial hypertension, diabetes and metabolic syndrome. Right heart morphology often involves the presence of adipose tissue, which can be quantified by non-invasive imaging methods. The last decade brought a wealth of new insights into the function and morphology of adipose tissue, with great emphasis on its role in the pathogenesis of heart disease. Cardiac adipose tissue is involved in thermogenesis, mechanical protection of the heart and energy storage. However, it can also be an endocrine organ that synthesises numerous pro-inflammatory and anti-inflammatory cytokines, the effect of which is accomplished by paracrine and vasocrine mechanisms. Visceral adipose tissue has several compartments that differ in their embryological origin and vascularisation. Deficiency of cardiac adipose tissue, often due to chronic pathological conditions such as oncological diseases or chronic infectious diseases, predicts increased mortality and morbidity. To date, knowledge about the influence of visceral adipose tissue on cardiac morphology is limited, especially the effect on the morphology of the right heart in a state of excess or deficient visceral adipose tissue.