Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease

Venous thromboembolism in critically ill patients affected by ARDS related to COVID-19 in Northern-West Italy

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. An association between increased venous thromboembolism in patients with pneumonia-related to COVID-19 has not yet been well described. PATIENTS AND METHODS: We aimed to illustrate cases of pulmonary thromboembolism in patients with acute respiratory distress syndrome related to COVID-19 treated in our intensive care unit. The medical records of patients affected by COVID-19 with acute respiratory distress syndrome in our institute from 1/3/2020 to 31/3/2020 were retrospectively reviewed. RESULTS: Our center registered a high prevalence of thromboembolic events among 62 patients affected by acute respiratory distress syndrome related to COVID-19 despite a regular antithrombotic prophylaxis. Out of these, 32 patients were transferred to other hospitals, and 30 were treated in our center. Venous thromboembolism was registered in 12 (19.3%) cases. In particular, 11 diagnoses of pulmonary embolism and 1 diagnosis of deep vein thrombosis were formulated. We described a case series of venous thromboembolism in nine patients treated in our Intensive Care Unit (ICU). Main pulmonary arteries were always involved in these patients. None of them died. CONCLUSIONS: In conclusion, critically ill patients with ARDS related to COVID-19 may have an increased risk of VTE that could be a leading cause of mortality. These patients require a high index of clinical suspicion and an accurate diagnostic approach, in order to immediately start an appropriate anticoagulant treatment

Microbiota and myopericarditis: The new frontier in the cardiological field to prevent or treat inflammatory cardiomyopathies in covid‐19 outbreak

Myopericarditis is an inflammatory heart condition involving the pericardium and myocardium. It can lead to heart failure, dilated cardiomyopathy, arrhythmia and sudden death. Its pathogenesis is mainly mediated by viral infections but also can be induced by bacterial infections, toxic substances and immune mediated disorders. All these conditions can produce severe inflammation and myocardial injury, often associated with a poor prognosis. The specific roles of these different pathogens (in particular viruses), the interaction with the host, the interplay with gut microbiota, and the immune system responses to them are still not completely clear and under investigation. Interestingly, some research has demonstrated the contribution of the gut microbiota, and its related metabolites (some of which can mimic the cardiac myosin), in cardiac inflammation and in the progression of this disease. They can stimulate a continuous and inadequate immune response, with a subsequent myocardial inflammatory damage. The aim of our review is to investigate the role of gut microbiota in myopericarditis, especially for the cardiovascular implications of COVID‐19 viral infection, based on the idea that the modulation of gut microbiota can be a new frontier in the cardiological field to prevent or treat inflammatory cardiomyopathies

Psychological distress among undergraduate dental students in Saudi Arabia and its coping strategies—a systematic review

The objective of this paper was to evaluate the studies that have reported on psychological issues among dental students in Saudi Arabia and to develop coping strategies to overcome these mental health-related issues. The present systematic review is in accordance with the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search for the articles was carried out in the electronic databases by four independent researchers. The data search was performed in the electronic search engines like PubMed, Google Scholar, Web of Science, Scopus, Medline, Embase, Cochrane and Saudi Digital Library for scientific research articles published from January 2000 until December 2020. STROBE guidelines were adopted for qualitative analysis of six articles which met the eligibility criteria. The analysis of the literature revealed that most of the studies included were conducted in the past 8 years in different regions of Saudi Arabia. Findings of this systematic review clearly state that dental students in Saudi Arabia experience higher levels of depression, stress and anxiety and stress during their education period, with a higher stress for female students compared to male students. There is an urgent need to introduce interventional programs and preventive strategies to overcome the long-term effects

Rapid clinical management of leishmaniasis in emergency department: A case report with clinical review of recent literature

Systemic or localized lympho-adenomegaly is a common cause of access to the emergency department (ED), and differential diagnosis is often complicated. The combination of anamnesis, physical examination, laboratory tests, and instrumental diagnosis are extremely important to orientate toward a rapid and correct therapy, even if a prompt discrimination of the etiology of this lymphadenomegaly is not often possible. Our aim with this review is to improve the management of a differential diagnosis between hematological and infective diseases as leishmaniasis in ED and suggest quick diagnostic techniques that might be useful for early identification. Together in the review, we describe a case report of a young man affected from visceral leishmaniasis who presented to our ED and was incorrectly addressed to the wrong ward for the study of his condition. Subsequently, we focus on the clinical presentation of visceral leishmaniasis and compare it to the most common differential diagnoses that are usually taken into account in the management of such patients

Usporedba dugotrajne primjene triju intrakanalnih lijekova na mikrotvrdoću i otpornost na lom korijenskog dentina: in vitro istraživanje

Objectives: The aim of this research was to evaluate the effect of long-term use of three intracanal medicaments on the radicular dentin microhardness and fracture resistance. Material and methods: A chemomechanical preparation was done using the Protaper rotary instruments up to F3. The teeth were stored in an incubator at 37°C at 100% humidity and were categorized in three groups by random allocation, namely: Triple Antibiotic Paste (TAP), Calcium hydroxide paste (Apexcal) and Ledermix. Following medicament application, the access openings of all teeth were sealed with 4 mm thickness of cavit. The samples were stored for periods of 1 week, 1 month and 3months. Two dentin cylinders measuring 5mm and 3mm were obtained from each sample. The cervical third was used for fracture resistance and the middle third was used for micro hardness evaluation. The microhardness testing was done using a Knoop microhardness tester, and the fracture resistance testing was done using the universal testing machine. Results: Calcium hydroxide showed maximally negative effect on the physical properties of radicular dentin compared to TAP (p= 0.0100 at one month and Ledermix (p=0.0001 at one month ). With an increase in the application time, there was an increased deterioration in the physical properties of radicular dentin. Conclusion: Long-term placement of calcium hydroxide, Triple Antibiotic Paste, and Ledermix (p= 0.0001at 3 months) significantly affects the microhardness and fracture resistance of radicular dentin.Cilj rada: Željelo se procijeniti kako dugotrajna upotreba triju intrakanalnh lijekova utječe na mikrotvrdoću i otpornost na lom radikularnog dentina.Materijal i metode: Kemomehanička preparacija obavljena Protaperovim rotirajućim instrumentima do F3. Zubi su zatim stavljeni u inkubator i čuvani na temperaturi od 37 °C u 100 posto vlažnom okružju te su slučajnim odabirom podijeljeni u tri skupine: trostruka antibiotička pasta (TAP), pasta od kalcijeva hidroksida (Apexcal), Ledermix. Nakon primjene lijekova svi su ulazni otvori zabrtvljeni 4 mm debelim slojem Cavita. Uzorci su zatim uskladišteni tjedan dana, mjesec dana i tri mjeseca. Od svakog uzorka uzeta su po dva dentinska cilindra debljine 3 i 5 mm. Za otpornost na lom korištena je cervikalna trećina, a za procjenu mikrotvrdoće srednja trećina. Mikrotvrdoća je ispitana testerom Knoop Microhardness, a otpornost na lom univerzalnim ispitnim uređajem. Rezultati: Kalcijev hidroksid najsnažnije je negativno djelovao na fizička svojstva radikularnog dentina u usporedbi s TAP-om (p = 0,0100 nakon mjesec dana) i Ledermixom (p = 0,0001 nakon mjesec dana). Kako se povećavalo razdoblje djelovanja, tako su se pogoršavala fizička obilježja radikularnog dentina. Zaključak: Dugotrajno korištenje kalcijeva hidroksida, TAP-a i Ledermixa (p = 0,0001 nakon 3 mjeseca) znatno utječe na mikrotvrdoću i otpornost na lom radikularnog dentina

Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study

In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6–11] days in early extubated patients versus 11 [6–15] days in standard weaning group (p = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation

Current drive at plasma densities required for thermonuclear reactors

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors

Corrigendum: Current drive at plasma densities required for thermonuclear reactors

Nature Communications 1: Article number: 55 (2010); Published: 10 August 2010; Updated:19 September 2013. In Fig. 3 of this Article, the colours of the blue and green curves were accidentally interchanged while the manuscript was being revised. In addition, the x axis labels on Fig. 4 should have read 'Frequency (MHz)'

Resolvins’ Obesity-Driven Deficiency: The Implications for Maternal–Fetal Health

Since pregnancy is already characterized by mild but significant inflammatory activity in physiological conditions, when complicated by obesity the probability of a persistent inflammatory state increases, with consequent multiple repercussions that add up to the complications associated with acute inflammation. In this context, the role of resolvins, specialized pro-resolving mediators (SPMs), deriving from omega-3 essential fatty acids, may be crucial. Indeed, differential production in numerous high-risk conditions associated with both childbirth and neonatal health, the correlation between maternal omega-3 intake and resolvin concentrations in maternal blood and at the placental level, and the high values found in breast milk in the first month of breastfeeding, are some of the most important hallmarks of these autacoids. In addition, a growing body of scientific evidence supports the lack of SPMs, at the level of immune-metabolic tissues, in the case of obesity. Furthermore, the obesity-related lack of SPMs seems to be decisive in the context of the current outbreak of COVID-19, as it appears to be one of the causes associated with the higher incidence of complications and negative outcomes of SARS-CoV-2 infection. The usefulness of metabolomics in this field appears clear, given that through the metabolome it is possible to observe the numerous and complex interactions between the mother, the placenta and the fetus in order to identify specific biomarkers useful in the prediction, diagnosis and monitoring of the various obstetric conditions. However, further investigations are needed in order to evaluate the possible use of some resolvins as biomarkers of maternal–fetal outcomes but also to establish adequate integration values in pregnant women with omega-3 fatty acids or with more active derivatives that guarantee optimal SPM production under risky conditions