Cardiac involvement with multisystem inflammatory syndrome in children can include coronary artery abnormalities, ventricular dysfunction, conduction abnormalities, arrhythmias, pericarditis, and myocarditis. We report the cardiac findings in 34 patients with multisystem inflammatory syndrome in children admitted to a single institution. We looked at patient age, sex, brain natriuretic peptide levels, troponin levels, ejection fraction, presence of pericardial effusion, valvular changes, need for inotropic agents, and electrocardiogram findings. Our data showed that elevated brain natriuretic peptide did not predict troponin elevation and vice versa. Additionally, troponin rise was not a reliable marker for decreased left ventricular ejection fraction. All changes tracked were proven to be transient and resolved after initiating steroids, Intravenous immune globulin (IVIG), and occasionally anakinra.

: Behçet's disease (BD) associated uveitis occurs in approximately 50-70% of patients. Ocular involvement in BD may induce a severe affection of visual function, leading to a considerable decrease in patients' quality of life. The risk for severe visual loss increases when the ocular posterior segment is involved and in patients with no adequate treatment.

Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger's Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex.Communicated by Ramaswamy H. Sarma.

Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly developed social skills and anxiety. Genetic predisposition plays a key role alongside the clinical findings, and clinicians must be aware of it as it can mimic other well-known skin conditions. Diagnosis is challenging both clinically and histologically. Clinically, it can mimic a severe form of atopic dermatitis, psoriasiform dermatitis overlapping with atopic dermatitis, or erythrokeratodermia variabilis. The difficulties in making histological diagnosis are similar, and it is often necessary to take several biopsies in order to clarify the diagnosis. Although retinoids are used for both psoriasis, erythrokeratodermia variabilis, and other congenital forms of keratodermia, the recommended treatment doses are different. This often results in poor treatment outcome. We present a 16-year-old patient previously diagnosed as erythrokeratodermia variabilis and treated with little to no improvement. Systemic therapy with acitretin 10 mg daily, local pimecrolimus 1%, emollients, and bilastine 20 mg once daily was initiated. Due to the limited application of retinoids and the difficulties in achieving permanent remission, modern medicine is faced with the challenge of seeking innovative therapeutic solutions. New hopes are placed on targeted or anti-cytokine therapy, based on inhibiting the inflammatory component of the disease. This article is mainly focused on innovative therapeutic options, including modern medications such as dupilumab, infliximab, secukinumab, anakinra, omalizumab, and others.

Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis characterised by clonal expansion of histiocytes in various organs. These induce an inflammatory environment, which leads to damage of the affected areas. Recently, a new disease entity was proposed encompassing key features of ECD but also of Rosai-Dorfman-Destombes disease, another histiocytosis. Mitogen-activated protein kinase kinase 1 (MAP2K1) mutations seem to present a specific genetic lesion for this subtype.Here, we describe a case of this new disease entity with clinical, radiological and genetic findings compatible with ECD but histological findings compatible with Rosai-Dorfman-Destombes disease. In particular, there were intraabdominal and retroperitoneal lesions, which tested positive for a (c.167A>C; p.Q56P) mutation of the MAP2K1 gene. On histological examination, S100-positive, giant histiocytes with focal emperipolesis of haematological cells in addition to infiltration by lymphocytes and granulocytes were seen.As described for this rare variant of ECD, there was also bilateral testicular infiltration. We also describe a manifestation of oligoarthritis in this patient with ECD.The patient was treated with methotrexate and prednisolone. While radiological response to this regime was excellent, arthritis persisted. We added anakinra, which induced a response of the arthritis for more than a year. Due to treatment failure therapy was switched to upadacitinib, which induced a remission of the arthritis as well.This case adds a rare phenotype to an already rare presentation of ECD. The patient responded to immunosuppressive therapy.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe, postinfectious manifestation of coronavirus disease 2019 (COVID-19) in the pediatric population. The disease is manifested by hyperinflammation and can result in cardiac dysfunction, coronary changes, and end-organ damage. Adequate timely treatment can prevent poor outcomes in the short term, but long-term data is lacking. Methods: A large single center MIS-C cohort was followed longitudinally after treatment with intravenous immunoglobulin (IVIG) ± glucocorticoids to determine the natural history of the disease and to describe improvement in laboratory markers and cardiac outcomes. Patient were stratified by disease severity and compared. Results: 137 patients were identified with demographics similar to previously described cohorts. Regardless of disease severity, when adequately treated, initial lab abnormalities rapidly improved by the 6-8 month follow-up period, with some resolved in as little as 1-2 weeks. Similarly, cardiac abnormalities improved quickly after treatment; all abnormalities resolved in this cohort by 1-2 months post-hospitalization. Conclusions: Although MIS-C is a serious sequela of COVID-19, when identified quickly and treated aggressively, laboratory abnormalities, coronary dilatation, and systolic dysfunction rapidly improve with minimal long-term morbidity or mortality.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in 'real-world' epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either anakinra or canakinumab. PFAPA patients seem to be less responsive to measles, mumps, and rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against hepatitis A. In consideration of the clinical frailty of both children and adults with SAIDs, all vaccinations remain 'highly' recommended in this category of patients despite the paucity of data available.

Inflammaging is related to cell senescence and reflects an erratic immune system, which promotes age-associated diseases. Exercise and nutrition, particularly omega-3 fatty acids, are able to affect inflammation. Therefore, we examined the effects of an 8-week exercise and dietary intervention on the inflammatory response in community-dwelling old adults. All participants received weekly vibration and home-based resistance exercise. Furthermore, participants were randomized to either a control, high-protein (1.2-1.5 g/kg), or high-protein, omega-3-enriched (2.2 g/day) diet. Before and after treatment, inflammatory markers in fasting serum and after whole-blood ex vivo lipopolysaccharide (LPS) stimulation were assessed. Gene expression levels of inflammatory markers were quantified in peripheral blood mononuclear cells (PBMC). Sixty-one participants (age: 70.6 ± 4.7 years; 47% men) completed the study. According to generalized linear mixed models, a high-protein, omega-3-enriched diet decreased circulating anti-inflammatory interleukin (IL-) 10 and IL-1 receptor antagonist (IL-1RA). Sex-stratified analyses showed also significantly reduced pro-inflammatory markers in men with a high-protein, omega-3-enriched diet. Gene expression of IL-1RA was significantly reduced after both protein-enriched diets compared with controls. In comparison to a high-protein diet, exercise alone showed lower LPS-induced release of c-c motif chemokine ligand-2 (CCL-2), which tended to be more pronounced in men compared with women. Eight weeks of a high-protein, omega-3-enriched diet combined with exercise decreased circulating anti-inflammatory markers, and pro-inflammatory markers in men. A high-protein diet attenuated anti-inflammatory markers on gene expression level in PBMC. Exercise alone resulted in a lower pro-inflammatory response to LPS-exposure in whole-blood cultures.

The human beta-coronavirus strain, OC43, provides a useful model for testing the antiviral activity of various agents. We compared the activity of several antiviral drugs against OC43, including remdesivir, chloroquine, interferon (IFN)-β, IFN-λ1, and IFN-λ4, in two distinct cell types: human colorectal carcinoma cell line (HCT-8 cells) and normal human bronchial epithelial (NHBE) cells. We also tested whether these agents mediate additive, synergistic, or antagonistic activity against OC43 infection when used in combination. When used as single agents, remdesivir exhibited stronger antiviral activity than chloroquine, and IFN-β exhibited stronger activity than IFN-λ1 or IFN-λ4 against OC43 in both HCT-8 and NHBE cells. Anakinra (IL-1 inhibitor) and tocilizumab (IL-6 inhibitor) did not mediate any antiviral activity. The combination of IFN-β plus chloroquine or remdesivir resulted in higher synergy scores and higher expression of IFN-stimulated genes than did IFN-β alone. In contrast, the combination of remdesivir plus chloroquine resulted in an antagonistic interaction in NHBE cells. Our findings indicate that the combined use of IFN-β plus remdesivir or chloroquine induces maximal antiviral activity against human coronavirus strain OC43 in primary human respiratory epithelial cells. Furthermore, our experimental OC43 virus infection model provides an excellent method for evaluating the biological activity of antiviral drugs.

Background: Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition and congestions for neurohormonal activation, heart failure is one of leading health conditions associated with high hospitalization and readmission rates, resulting in poor quality of life. In light of this, this article serves to demonstrate the effect of anakinra as one of the treatment paradigms for HF to explore the need for advanced novel interventions. Methods: We conducted a search in five electronic databases, including Embase, MEDLINE, Cochrane, Scopus, and PubMed, for RCTs (randomized controlled trials) evaluating the effects of anakinra against placebo in HF. Meta-analysis was performed using RevMan version 5.4. Results: Eight RCTs were obtained and included for analysis in this study. The results demonstrate that anakinra significantly reduces the levels of CRP (C-reactive protein), with significant difference between anakinra- and placebo-treated groups. Analyses also show that CRP failed to cause an improvement in peak oxygen consumption and ventilatory efficiency. Additionally, the treatment-related adverse events were insignificant. Some considerable limitations are that the same set of researchers were involved in most of the studies; hence, more independent studies need to be encouraged. Conclusion: Anakinra was associated with a reduction in CRP levels, indicating some anti-inflammatory effects but no effect on function, exercise capacity, and adverse effects.

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL-6, and IL-10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies.

Multisystem inflammatory syndrome in children (MIS-C) is a newly identified clinical entity still not very well known in terms of epidemiology, pathogenesis, and long-term outcome. Pulmonary involvement with acute respiratory failure is an unusual life-threatening complication of MIS-C, often a reason for admission to the pediatric intensive care unit (PICU) and the use of mechanical ventilation. We present a case of a 7-year-old male patient, previously healthy, hospitalized for MIS-C, treated with intravenous immunoglobulins (IVIG), high dose methylprednisolone, and anakinra. After 2 days of the aforementioned therapy, the patient presented with hypoxia (SatO2: 85% in ambient air room) and breathing difficulties. A chest computed tomography (CT) scan showed the presence of multiple bilateral basal parenchymal thickening and small basal pleural effusion and an arterial blood gas analysis revealed severe hypoxia (PaO2/FiO2 ratio, 170 mmHg). Because of a worsening of respiratory distress, the patient was transferred to the PICU, where invasive mechanical ventilation and a continuous infusion of anakinra (12 mg/kg/day) were started. An echocardiogram was performed, which showed an increase in pulmonary pressure (40 mmHg) with normal heart ejection fraction (55%), and the hypothesis of pulmonary vasculitis involving the pulmonary arterioles was made. Therefore, therapy with sildenafil (0.15 mg/kg/day) was promptly set up, with an immediate improvement of the clinical picture of respiratory failure, reduction of pulmonary pressure (23 mmHg), and subsequent extubation at 36 h with a regular clinical course until discharge. As far as we know, our case represents the first report of pulmonary vasculitis in an MIS-C patient. The use of sildenafil and high-dose continuous anakinra may represent a rescue therapy in cases of MIS-C with pulmonary vasculitis or with difficulty in extubation, allowing a short-term hospitalization in intensive care and improving the long-term outcome in these patients.

Mice with SHP1 proteins, which have a single amino acid substitution from tyrosine-208 residue to asparagine (hereafter Ptpn6spin mice), develop an autoinflammatory disease with inflamed footpads. Genetic crosses to study CD47 function in Ptpn6spin mice bred Ptpn6spin × Cd47-/- mice that were not born at the expected Mendelian ratio. Ptpn6spin bone marrow cells, when transferred into lethally irradiated Cd47-deficient mice, caused marked weight loss and subsequent death. At a cellular level, Ptpn6-deficient neutrophils promoted weight loss and death of the lethally irradiated Cd47-/- recipients. We posited that leakage of gut microbiota promotes morbidity and mortality in Cd47-/- mice receiving Ptpn6spin cells. Colonic cell death and gut leakage were substantially increased in the diseased Cd47-/- mice. Last, IL-1 blockade using anakinra rescued the morbidity and mortality observed in the diseased Cd47-/- mice. These data together demonstrate a protective role for CD47 in tempering pathogenic neutrophils in the Ptpn6spin mice.