Stress-Modulated Pathways

Stress is a condition or an experience that is pervasive throughout human life. While there are many definitions of stress, a common notion is that stress is processed in the central nervous system and has effects on health that are mediated by stress-modulated pathways. Several brain areas, such as the amygdala and the broader limbic system, are involved in interpreting situations as potentially stressful. The signals of these areas converge in the hypothalamus, which orchestrates peripheral stress-modulated pathways, mainly the hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS). Health effects of stress are mediated by long-term alterations of basic stress system activity, which has downstream effects on pathophysiological pathways such as the inflammatory system.

Coagulopathy and COVID-19

SARS-CoV-2 infection is associated with frequent thrombotic events, at the micro and macro-vascular level, due to the perpetuation of a state of hypercoagulability. The so-called ‘COVID-19 associated coagulopathy’ (CAC) represents a key aspect in the genesis of organ damage from SARS-CoV-2. The main coagulative alterations described in the literature are represented by high levels of D-dimer and fibrinogen. Although CAC has some common features with disseminated intravascular coagulation and sepsis-induced coagulopathy, there are important differences between these clinical pictures and the phenotype of CAC is unique. The pathogenesis of CAC is complex and is affected by the strong interconnection between the inflammatory system and coagulation, in the phenomenon of immunothrombosis and thrombo-inflammation. Several mechanisms come into play, such as inflammatory cytokines, neutrophils, the complement system as well as an alteration of the fibrinolytic system. Finally, an altered platelet function and especially endothelial dysfunction also play a central role in the pathophysiology of CAC. Heparin has several potential effects in CAC, in fact in addition to the anticoagulant effect, it could have a direct antiviral effect and anti-inflammatory properties. The high incidence of thrombo-embolic phenomena despite the use of antithrombotic prophylaxis have led some experts to recommend the use of anticoagulant doses of heparin, but at present the optimal anticoagulant regimen remains to be determined.

A Brief Review on Covid-19 Effects in Children and Treatment Methods

As there is an outbreak of novel corona virus in 2019 it has spread globally that resulted in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic and mostly there is limited data provided on children. The main aim of this review is to provide a knowledge on introduction, epidemiology, pathogenesis, transmission, clinical manifestations, laboratory findings, treatment of COVID-19 in children. And it also includes latest statistical data of children prone to COVID-19. Besides respiratory and GI symptoms atypical features such as chilblains and multi-inflammatory system are also reported. pathophysiology gives information regarding the life cycle of virus in hostcell and epidemiology explains the different types of viruses affecting the respiratory system. The clinical signs and symptoms are almost similar to the adults but they are in mild, and most of the children affected with Covid-19 are asymptomatic. This review study makes a medical practitioner to have a quick, practical approach to the disease to use in different scopes, especially in pediatric medicine.

The Role of Interleukin-27 in Atherosclerosis: A Contemporary Review

Atherosclerosis is a chronic inflammation characterized by an imbalance between inhibitors and stimulators of the inflammatory system that leads to the formation of atherosclerotic plaques in the vessel walls. Interleukin (IL)-27 is one of the recently discovered cytokines that have an immunomodulatory role in autoimmune and inflammatory diseases. However, the definite role of IL-27 in the pathogenesis of atherosclerosis remains unclear. Recent studies on cardiomyocytes and vascular endothelium have demonstrated mechanisms through which IL-27 could potentially modulate atherosclerosis. Upregulation of the IL-27 receptor was also observed in the atherosclerotic plaques. In addition, circulatory IL-27 levels were increased in patients with acute coronary syndrome and myocardial infarction. A regenerative, neovascularization, and cardioprotective role of IL-27 has also been implicated. Future studies are warranted to elucidate the biologic function and clinical significance of IL-27 in atherosclerosis.

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient’s outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.

Immuno-Inflammatory Characteristics in Low Severity COVID-19 Patients with Digestive Symptoms

Aim. The outbreak of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic, with the main manifestations being of respiratory nature, including pneumonia. It is noteworthy that digestive symptoms are also observed in COVID-19 patients. In this article, we describe the immuno-inflammatory characteristics of low severity COVID-19 patients with digestive symptoms. Methods. Patients with mild symptoms of COVID-19 were split into three groups based on the patients’ symptoms. The first group displayed digestive symptoms only, the second group displayed respiratory symptoms only, and the last group displayed both digestive and respiratory symptoms. Patients were discharged based on negative results of rRT-PCR testing for SARS-CoV-2 from at least two sequential respiratory tract specimens collected ≥24 hours apart. Multiorgan function and immuno-inflammatory characteristics were analyzed for all of the three groups. Results. Mild liver damage and activation of the immuno-inflammatory system were the most common abnormalities observed in patients with mild COVID-19 symptoms but no significant differences were found (P>0.05). Patients with digestive symptoms were more likely to have slightly higher and later peak values of inflammatory cytokines during the subsequent course of disease (P<0.05). In addition, a significant correlation between IL-2 and TNF level was found in the first group which included patients with digestive symptoms only (P<0.05). Conclusions. Patients with mild cases of COVID-19 only displaying digestive symptoms are a special subtype. Patients in this group were more likely to have slightly higher and delayed peak values of inflammatory cytokines during the subsequent course of the disease. Prevention and clinical management of this type should be taken into consideration.

Immuno-inflammatory Characters in Low Severity COVID-19 Patients with Digestive Symptoms

Background: Coronavirus disease 2019 (COVID-19) is an emerged infection raised widely concerns for pneumonia and respiratory manifestations. It is noteworthy that digestive symptoms are frequently observed in COVID-19 patients. We sought to describe the immune-inflammatory characteristics of COVID-19 patients with digestive symptoms and mild disease severity.Methods: We designated enrolled mild patients into three subtypes depending on the patients with or without digestive symptoms, including Digestive only (digestive symptoms only), Respiratory only (respiratory symptoms only) and Digestive+ Respiratory (Both digestive and respiratory symptoms). Patient discharge was based on negative results of rRT-PCR testing for SARS-CoV-2 from at least two sequential respiratory tract specimens collected ≥24 hours apart. The multiorgan function, immune-inflammatory characteristics were analyzed among three groups.Results: Mild liver damage and the activation of immuno-inflammatory system are the most abnormalities in mild patients but no significant differences were found (p＞0.05). Compared with the Respiratory only group, patients with digestive symptoms were more likely to have slightly higher and later peak values of inflammatory cytokines during the subsequent course of disease(P＜0.05). Additionally, we also found that there was a significant correlation between IL-2 and TNF level in the Digestive only cases (P＜0.05). Conclusions: Mild patients only/accompanied with digestive symptoms are a special subtype of COVID-19. Patients in this group were more likely to have slightly higher and later peak values of inflammatory cytokines during the subsequent course of disease. The prevention and clinical management of this type should be taken into consideration.

Cytokine storm and colchicine potential role fighting SARS-CoV-2 pneumonia

For some patients with SARS-CoV-2, the worst clinical damage is not caused by the virus itself, but by an overactive inflammatory state. In fact, in some people the immune system goes into overdrive and launches a large-scale assault on the tissue known as cytokine storm. This excessive inflammatory/immune reaction can damage tissue and eventually kill people. Evidence shows that blocking such cytokine storms can be effective and trials are underway to test drugs that act by reducing cytokine response, such as tocilizumab and sarilumab which bind interleukin 6 (IL-6), or anikinra which is the interleukin 1 receptor antagonist (IL-1). However, other drugs that block the cytokine cascade can also be considered. In this article we describe the scientific and molecular motivation for the use of drugs that act by modulating the hyperactive inflammatory system in severe patients suffering from SARS-CoV-2, considering in particular an old drug that has been in use for many years for other therapeutic indications such as colchicine, and that could be favourable to its use, with low cost and good tolerability.

A narrative review of antithrombin use during veno-venous extracorporeal membrane oxygenation in adults: rationale, current use, effects on anticoagulation, and outcomes

Background: During extracorporeal membrane oxygenation, the large contact surface between the blood and the extracorporeal circuit causes a continuous activation of coagulation and inflammation. Unfractionated heparin, a glycosaminoglycan that must bind to antithrombin as a cofactor, is currently the standard anticoagulant adopted during extracorporeal membrane oxygenation. Antithrombin, beyond being a potent natural anticoagulant, acts in the cross-talk between coagulation and inflammatory system through anticoagulation and coagulation-independent effects. Objectives: In this review, we describe, in the adult setting of veno-venous extracorporeal membrane oxygenation, the pathophysiological rationale for antithrombin use, the current practice of administration, and the effects of antithrombin on anticoagulation, bleeding, and outcomes. Data sources: Studies on adults (18 years or older) on veno-venous extracorporeal membrane oxygenation published from 1995 to 2018 in order to evaluate the use of antithrombin. Results: In adults on veno-venous extracorporeal membrane oxygenation, antithrombin supplementation has a highly pathophysiological rationale since coagulation factor consumption, systemic inflammatory response syndrome, and endothelial activation are triggered by extracorporeal membrane oxygenation. Eleven articles are focused on the topic but among the authors there is no consensus on the threshold for supplementation (ranging from 70% to 80%) as well as on the dose (rarely standardized) and time of administration (bolus vs continuous infusion). Consistently, antithrombin is considered able to achieve better anticoagulation targets in or not in the presence of heparin resistance. The impact of antithrombin administration on bleeding still shows contrasting results. Conclusion: Antithrombin use in veno-venous extracorporeal membrane oxygenation should be investigated on the threshold for supplementation, dose, and time of administration.