SARS-CoV-2 and Pre-Tamponade Pericardial Effusion. Could Sotos Syndrome Be a Major Risk Factor?

Pericarditis with pericardial effusion in SARS CoV-2 infection is a well-known entity in adults. In children and adolescents, only a few cases have been reported. Here, we present here a case of a 15-year-old girl affected by Sotos syndrome with pre-tamponed pericardial effusion occurred during SARS-CoV-2 infection. A possible relation between SARS-CoV-2 pericarditis and genetic syndromes, as a major risk factor for the development of severe inflammation, has been speculated. We emphasize the importance of active surveillance by echocardiograms when SARS-CoV-2 infection occurs in combination with a genetic condition.

Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection

Introduction: Recombination-activating gene 1 (Rag1) and Rag2, which are essential in V(D)J recombination, play a crucial role in B and T cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including MIP-1α, IP-10, IFN-α, IFN-γ, and TNF-α, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

Immunomodulatory Nanoparticles Mitigate Macrophage Inflammation via Inhibition of PAMP Interactions and Lactate-Mediated Functional Reprogramming of NF-κB and p38 MAPK

Inflammation is a key homeostatic process involved in the body’s response to a multitude of disease states including infection, autoimmune disorders, cancer, and other chronic conditions. When the initiating event is poorly controlled, severe inflammation and globally dysregulated immune responses can occur. To address the lack of therapies that efficaciously address the multiple aspects of the dysregulated immune response, we developed cargo-less immunomodulatory nanoparticles (iNPs) comprised of poly(lactic acid) (PLA) with either poly(vinyl alcohol) (PVA) or poly(ethylene-alt-maleic acid) (PEMA) as stabilizing surfactants and investigated the mechanisms by which they exert their inherent anti-inflammatory effects. We identified that iNPs leverage a multimodal mechanism of action by physically interfering with the interactions between pathogen-associated molecular patterns (PAMPs) and bone marrow-derived macrophages (BMMΦs). Additionally, we showed that iNPs mitigate proinflammatory cytokine secretions induced by LPS via a time- and composition-dependent abrogation of NF-κB p65 and p38 MAPK activation. Lastly, inhibition studies were performed to establish the role of a pH-sensing G-protein-coupled receptor, GPR68, on contributing to the activity of iNPs. These data provide evidence for the multimodal mechanism of action of iNPs and establish their potential use as a novel therapeutic for the treatment of severe inflammation.

Possibilities and problems of mycotic keratites therapy in the hospital

Fungi are most common cause of severe inflammation of the cornea, resulting in blindness and loss of vision [6]. According to various researchers, fungi are the cause of keratitis in 40-50% of all microbial keratitis cases [1, 3]. Treatment of keratomycosis in the Russian Federation is carried out by methods other than intended. Lack of skills and availability of diagnostics, official etiotropic therapy for use in ophthalmology for ophthalmologists, unequal conditions in the fight against ophthalmomycosis. This is partly due to the lowered level of «myco-alertness», which leads to long-term ineffective «healing» of antibacterial drops, the duration of the patient’s suffering and results in the loss of the eye functionally and — in some cases — anatomically [7]. Global eye removal counts revealed that this method was used in 8-11%, which represents an annual loss of 84,143-115,697 eyes [6]. Key words: keratomycosis, mycotic keratitis, treatment, therapy.

EP.TH.15Review of cholecystectomies laparoscopic & open plus conversion rate in a five year period

Aim Look & audit our practice of cholecystectomy & try to identify areas that require improvement Method Look at all cholecystectomies, laparoscopic & open in 5 years from January 2014 till December 2018, we looked at demographics, number of operations per year, conversion & re-admission rate, information collected from electronic note record Results male to female ratio similar to national figures, number of laparoscopic operations (2422 in that period, 61 cases converted, conversion rate 2.5%) going up steadily over the 5 years while open & conversion rate are dropping significantly, early re-admission rate higher than national figure, reasons for conversion determined & analysed Reasons for doing it open from the start also determined, commonest cause for conversion in our trust is: previous surgery/adhesions, obscure anatomy & severe inflammation of gall bladder . Commonest cause of re-admission is pain followed by wound complications collections retained stone & bile leak. Number of open cholecystectomies was 22 in 2104 dropping to only 2 in 2018. 3 deaths occurred in the group giving rise to a mortality of 0.12% Conclusion Majority of cases attempted laparoscopically & most patients discharged home within 48 hours, our conversion rate is low = 2.5% with consultants with higher number of operation having less conversions, ours re-admission rate is high mainly for pain, our mortality is low. We recommend looking closer at re-admissions to see how that number could be reduced.

Management of Hunner Lesion in Interstitial Cystitis/Bladder Pain Syndrome Patients

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by chronic pelvic pain related to the bladder. One phenotype of IC/BPS is the Hunner lesion type IC/BPS. Hunner lesion exhibits typical features such as mucosal ulceration, fibrosis, and severe inflammation. The tissue surrounding the Hunner lesion may show lymphoplasmacytic infiltrates, and mast cells are increased in the lamina propria. In this chapter, we discuss intravesical treatment, endoscopic treatment, and partial cystectomy with augmentation cystoplasty for the management of Hunner lesion in IC/BPS patients.

Association of Serum Neuron-Specific Enolase and C-Reactive Protein With Disease Location and Endoscopic Inflammation Degree in Patients With Crohn's Disease

Objective: The objective of this study was to explore the association between serum markers neuron-specific enolase (NSE) and C-reactive protein (CRP) with intestinal lesion location and degree of inflammation in patients with Crohn's disease (CD).Design: The levels of serum NSE, CRP, and fecal calprotectin (FC) in patients with CD were analyzed retrospectively. The severity of inflammatory lesions in the intestinal wall was accessed using the Simple Endoscopic Score for Crohn's disease (SES-CD).Results: The levels of NSE in patients with CD were higher than those of healthy individuals (14.87 vs. 12.68 ng/ml, P < 0.001). The levels of CRP in patients with CD were higher than those of healthy individuals (12.30 vs. 3.40 mg/l, P < 0.001). The FC levels in patients with CD were higher than those of patients with non-inflammatory bowel disease (1,143.90 vs. 114.21 μg/g, P < 0.05). The levels of NSE in CD with ileal lesions and simultaneous ileal and colon lesions were significantly higher than those in patients with CD with colonic lesions. However, the CRP was higher in patients with colonic lesions than those with ileal lesions. The levels of NSE in patients with severe inflammation were higher than those in patients with moderate inflammation (15.95 vs. 13.89 ng/ml, P < 0.05). Similarly, the NSE levels in patients with CD with severe inflammation were higher than those in patients with CD with mild inflammation (15.95 vs. 13.53 ng/mL, P < 0.05). The levels of CRP in severe inflammation were higher than those in moderate inflammation (29.80 vs. 19.60 mg/l, P < 0.05). In addition, the CRP levels in severe inflammation were higher than those in mild inflammation (29.80 vs. 5.86 mg/l, P < 0.05). ROC curve analysis showed that when NSE was combined with CRP for distinguishing between patients with CD and those without CD, sensitivity increased to 80.41%, specificity increased to 74.66%, and a highest AUC was equal to 0.843.Conclusion: Our study shows that serum NSE and CRP can be used to assess the severity of CD as well as the location of intestinal involvement. Therefore, NSE and CRP could be used as the non-invasive tests in detecting the location and severity of disease in patients with CD in daily routine practice.

Neutrophils Affect IL-33 Processing in Response to the Respiratory Allergen Alternaria alternata

Future precision medicine requires further clarifying the mechanisms of inflammation in the severe endotypes of chronic airway diseases such as asthma and chronic rhinosinusitis (CRS). The presence of neutrophils in the airways is often associated with severe airway inflammation, while their precise contribution to the severe inflammation is largely unknown. We aimed to study the role of neutrophils in BALB/c and C57BL/6 mice exposed to Alternaria alternata (Alt). The mice were exposed to Alt extract for twelve hours or ten days to induce allergic airway inflammation. C57BL/6 mice exposed to Alt responded with eosinophilic infiltration and the characteristic IL-5 upregulation. In contrast, the inflammatory response to Alt extract in BALB/c mice was characterized by a neutrophilic response, high levels of G-CSF, and elastase in the lungs. The lack of neutrophils affected the processing of IL-33 in BALB/c mice, as was demonstrated by depletion of neutrophils through intraperitoneal injections of anti-Ly6G antibody. Our data identifies the key role of neutrophils in airway inflammation through IL-33 cleavage in the Alt-induced airway inflammation in mice, which could potentially underline the different endotypes in human disease.

Can Polyphenols be Used as Anti-Inflammatory Agents against Covid-19 (SARS-CoV-2)-Induced Inflammation?

Covid-19 is the causative agent of a beta coronavirus that causes severe inflammatory pneumonia, so excessive inflammation is considered a risk factor for the disease. In Covid-19 disease, an inflammatory response develops in the body. It has been reported as a result of various studies that this response causes damage to various organs and tissues, especially the lungs. According to reports, cytokine storms are largely responsible for death in such patients. Some of the consequences of severe inflammation and cytokine storms include acute respiratory distress syndrome, acute lung injury, and multiple organ dysfunction syndromes. Many studies are showing that there may be various agents to prevent or treat these effects of Covid-19 disease. Some of these agents are phenolic compounds. Phenolic compounds are the most abundant substances in vegetables and fruits. Inflammasomes, their function. It has been stated that phenolic compounds inhibit inflammation by inhibiting cytosolic multiprotein complexes that assemble in response to cytosolic pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) to form active forms of IL-1β and IL-18. It suggested that Apigenin, Resveratrol, Morin, and Silymarin an anti-inflammatory, antioxidant, anti-viral, and anti-microbial compound could be a potential therapeutic agent for severe inflammation from Covid-19.