Early Anti-inflammatory Therapy Research Articles

Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.

Interleukin-6 plasma levels are elevated in patients with acute myocardial infarction and predict death or recurrent infarction within 1 year - a case-control study

Abstract Background Acute myocardial infarction (AMI) harbours marked inflammatory components. While cytokines of the same family have been causally related to patient outcome, the role of interleukin (IL)-6 in AMI remains incompletely understood. Recent trials suggest benefits of inhibiting IL-6 in patients with ST-segment elevation myocardial infarction (STEMI). In patients at high atherosclerotic risk, IL-6 blockade reduces markers of inflammation and thrombosis. Purpose This study aimed to assess the levels of IL-6 in AMI patients and their predictive value. Methods 160 cases (recurrent AMI or death within 1 year) and 160 matched controls were selected from the prospective, multicentric SPUM-ACS Cohort. All patients had an AMI (STEMI or NSTEMI) as initial event and underwent percutaneous coronary intervention (PCI) within 24h of symptom onset. Blood samples were drawn before PCI and biomarker plasma levels were assessed (mesoscale). Comparisons were made with age- and sex-matched healthy blood donors (HD). IL-6 levels are presented as medians and interquartile ranges. Cases, controls and HD were compared using the Kruskal-Wallis test. Correlations of baseline variables to IL-6 levels within cases and controls were assessed by linear regression analyses. Patients were divided into those with higher or lower IL-6 levels according to the median IL-6 level. Kaplan-Meier (KM) analyses for the combined endpoint of death or recurrent AMI were performed. Results The overall median IL-6 level was 21.3pg/ml. Patients with higher IL-6 had more previous AMI (n=22, 14%) than patients with lower IL-6 (n=12, 7%, p=0.045). Patients with increased IL-6 had more previous PCI (n=30, 20%) than patients with lower IL6 (n=19, 11%, p=0.045). Both cases and controls showed higher levels of IL-6 than HD (cases: 25.7pg/ml [14.8–81.6], controls: 20.0pg/ml [11.3–40.1], HD: 5.9pg/ml [3.6–9.9]; cases/controls vs. HD: p<0.0001). Among AMI patients, cases showed higher IL-6 levels than controls (p=0.030) (Figure 1). Within cases and controls, IL-6 was related to IL-1beta (r=0.628, p<0.001), IL-1alpha (r=0.174, p=0.002) and IL-1 receptor antagonist (r=0.422, p<0.001). IL-6 was related to neutrophil/lymphocyte ratio (r=0.147, p=0.016), but not to high-sensitivity C-reactive protein (r=0.087, p=0.142) or N-terminal pro B-type natriuretic peptide (r=0.091, p=0.118). IL-6 was related to Killip Class upon presentation (r=0.190, p<0.001). KM analyses showed significantly higher rates of death or recurrent AMI within 1 year for patients with higher IL-6 (log-rank p=0.006, Figure 2), with early divergence of the curves. Conclusions IL-6 is markedly higher in patients with AMI compared to healthy controls and predicts death or recurrent AMI within 1 year. IL-6 might be a valuable target for early anti-inflammatory therapy to patients with AMI. A deeper understanding of factors influencing IL-6 levels may help select those patients that will benefit most from such treatment.Figure 1:Cases vs. Controls vs. HDFigure 1:Kaplan-Meier Analysis

Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN.MethodsTen patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed.ResultsOcular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13.ConclusionsSevere pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Efficacy and Safety of Early Anti-inflammatory Drug Therapy for Secondary Injury in Traumatic Brain Injury.

Brain injury following head trauma occurs in 2 stages, namely an early stage attributable to mechanical damage and a delayed stage resulting primarily from neuroinflammation. In this study, we examined early proinflammatory cytokine upregulation in an animal model of traumatic brain injury (TBI) and examined the effects of early anti-inflammatory therapy on neuroinflammation, neuropathology, and systemic inflammatory activity. Seven-week-old C57BL/6 mice (20 g-25g) were subjected to sham treatment or closed skull impact from a 30-g round weight dropped 15cm onto the cortical midpoint. Model mice were then randomly assigned to receive intraperitoneal phosphate-buffered saline (control), 20mg/kg cyclosporine A, 2mg/kg dexamethasone, or 5mg/kg cholecalciferol 1hour post-TBI. Body weight, brain weight, cytokine expression in the brain and draining lymph nodes (DLNs), and histopathological changes were measured at multiple times post-TBI. Body weight did not significantly differ among the groups, whereas the brain-to-body weight ratio was significantly lower in the control group 7days post-TBI. The peak expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in the brain and DLNs 6hours post-TBI was significantly lower in the dexamethasone and cyclosporine A groups. Conversely, peak IL-10 expression in the brain and DLNs was elevated in the cholecalciferol group. Control mice exhibited earlier and more severe neuroinflammatory damage than those in the experimental groups. The administration of anti-inflammatory drugs or vitamin D analogs in the early period following TBI might help to reduce secondary injury from neuroinflammation.

Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors

Sepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors. To describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial. This prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022. The intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo. Cognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization. After exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups. In survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors. ClinicalTrials.gov Identifier: NCT03509350.

Early detection of inflammation-prone STEMI patients using the CRP Troponin Test (CTT)

Abstract Background Elevated concentrations of C-reactive protein (CRP) early after acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI using the CRP Troponin test (CTT) and determine their short- and long-term outcome. Material and methods We retrospectively examined 1,186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 hours apart), all within the first 48 hours of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Results Patients with high CRP concentrations (above 90th percentile, >33mg/L) had higher 30 day- and all-cause mortality rates regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs 2.7%, p<0.01. Furthermore, patients with both high CRP and high Troponin levels on their second measurement had the highest 30-day mortality rates compared to the rest of the cohort; 21.4% vs. 3.7%, p<0.01. These patients also had the highest all-cause mortality rates after a median follow up of 4.5 years compared to the rest of the cohort; 42.9% vs 12.7%, p<0.01 (Figure 1). Conclusions In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CRP Troponin-test (CTT) as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-IL-1β agents. Funding Acknowledgement Type of funding sources: None.

Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge.

Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12–18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.

Early Detection of Inflammation-Prone STEMI Patients Using the CRP Troponin Test (CTT).

Elevated concentrations of C-reactive protein (CRP) early during an acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST-segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI by using a combined CRP and troponin test (CTT) and determine their short- and long-term outcome. We retrospectively examined 1186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 h of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Patients with high CRP concentrations (above 90th percentile, >33 mg/L) had higher 30 day and all-cause mortality rates compared to the rest of the cohort, regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs. 2.7%, p < 0.01. Furthermore, patients with both high CRP and high troponin levels on their second measurement had the highest 30-day mortality rates compared to the rest of the cohort; 21.4% vs. 3.7%, p < 0.01. These patients also had the highest all-cause mortality rates after a median follow-up of 4.5 years compared to the rest of the cohort; 42.9% vs. 12.7%, p < 0.01. In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CTT as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-interleukin-1ß agents.

Efficacy of anakinra on rebound of multisystem inflammatory syndrome.

Efficacy of anakinra on rebound of multisystem inflammatory syndrome.

Home pharmacological therapy in early COVID-19 to prevent hospitalization and reduce mortality: Time for a suitable proposal.

The COVID‐19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post‐mortem autopsy was performed on a very modest number of patients who died from COVID‐19 infection, leading to a first confirmation of an immune‐thrombosis of the lungs as the major COVID‐19 pathogenesis, likewise for SARS. Since then (June–August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti‐inflammatory, anti‐platelet, anticoagulant and antibiotic therapy confirmed that COVID‐19 was an endothelial inflammation with immuno‐thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immune‐thrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti‐inflammatory therapy may treat endothelia inflammation and immune‐thrombosis caused by COVID‐19, by using drugs we are going to recommend in this paper.

Possi bilities and perspectives of colchicine application in complex therapy in patients with COVID-19

The new coronavirus infection, which has become a pandemic, is greatly increasing interest in the search for new pharmacological drugs with antiviral and anti-infl ammatory properties. Colchicine, which has been used in medicine for centuries and has been mainly known as arthrifuge, has come to be unexpectedly considered as a drug aff ecting the cumulative endpoint in outpatients, including death and hospitalization requirement in a recent large, well-planned, randomized controlled trial. The article provides data on the pharmacodynamics of the drug, which consists in blockade of infl ammasome activation in patients with COVID-19, and an eff ective impact on the mechanisms of “cytokine storm” — a predictor of acute respiratory distress syndrome and sepsis as a major cause of multi-organ lesions and death. The information that its spectrum of anti-infl ammatory activity may explain the vasoprotective eff ects in patients with coronary heart disease (CHD) who underwent acute infarction in the COLCOT study, is particularly attractive from the point of view of the perspectives for the oral colchicine application in COVID-19. High tolerability of the drug, the absence of severe adverse reactions, simple dosing regimen, low cost of colchicine, the absence of signifi cant drug interactions are additional advantages. The authors of this article believe that this information is suffi cient for planning a study of the eff ectiveness of colchicine as an element of complex therapy in hospitalized patients with COVID-19 in combination with acute coronary syndrome, including the need for percutaneous coronary intervention. Early anti-infl ammatory therapy in patients with COVID-19 is still not recommended, despi te th e fact t h at there comes an understanding of its necessity. And in this situation, colchicine has the potential to challenge.

Major predictive risk factors for cytokine storm in COVID-19 patients (Clinical trials)

AIM: Searching for predictors of cytokine storm in patients with COVID-19 and creating a risk scale for this complication for practical implementation.&#x0D; MATERIALS AND METHODS: The study included 458 patients with confirmed COVID-19 with signs of viral lung lesion according to computer tomography. The patients were divided into 2 groups: with a stable course of moderate severity (100 patients) and with progressive moderate, severe and extremely severe course (358 patients).&#x0D; RESULTS: It has been established that the main risk factors for the development of cytokine storm in COVID-19 patients are interleukin-6 concentration 23 pg/ml, the dynamics of the index according to the NEWS scale 0, ferritin concentration 485 ng/ml, D-dimers 2,1, C-reactive protein 50 mg/l, the number of lymphocytes in the blood 0,72 ∙ 109/l, age 40 years. Cytokine storm incidence correlates with an increase in the number of risk factors. For practical use the scale is applied in 3 groups. In the patients of the first group (0-1 factor) almost no cytokine storm risk was detected, in the second group (2-3 factors) the probability of a storm was 55 % (increased by 35.5 times), in the third group (4 risk factors) reaches 96 % (increased by 718 times).&#x0D; CONCLUSIONS: Diagnostic and monitoring criteria of cytokine storm in the patients with COVID-19 were established. The developed prognostic scale allows to identify patients at high risk of developing cytokine storm for early anti-inflammatory therapy.

Major predictive risk factors for а cytokine storm in COVID-19 patients (a retrospective clinical trials)

Background: According to WHO, as of March 31, 2021, 127 877 462 confirmed cases of the new COVID-19 coronavirus infection were registered in the world, including 2 796 561 deaths (WHO Coronavirus Disease). COVID-19 is characterized by a wide range of clinical manifestations, from asymptomatic to a rapid progression to severe and extremely severe. Predictive biomarkers for the early detection of high-risk individuals have become a matter of great medical urgency. Aims: Search for the predictors of a cytokine storm in patients with COVID-19 infection and creation of a risk scale of this complication for practical applications. Methods: The study included 458 patients with confirmed COVID-19 infection with signs of viral lung lesions according to the computer tomography data. The patients were divided into 2 groups: those with a stable course of moderate severity (100 patients) and those with progressive moderate, severe and extremely severe course (358 patients). Results: It has been established that the main risk factors for the development of a cytokine storm in COVID-19 patients are the following: interleukin-6 concentration 23 pg/ ml, dynamics of the index on the NEWS scale 0, ferritin concentration 485 ng/ml, D-dimer concentration 2.1, C-reactive protein concentration 50 mg/l, number of lymphocytes in the blood 0.72109/l, age 40 years. The cytokine storm incidence correlates with an increase in the number of risk factors. For the practical testing the scale was applied in 3 groups. In patients of the first group (01 factor) almost no cytokine storm risk was found, in the second group (2 -3 factors) the probability of the storm was 55% (increase by 35.5 times), in the third group (4 risk factors) it reached 96% (increase by 718 times). Conclusion: The diagnostic and monitoring criteria of a cytokine storm have been established in patients with COVID-19 infection. The developed prognostic scale allows identification of patients at high risk of developing a cytokine storm so that early anti-inflammatory therapy could be started.

The necessity of early anti-inflammatory therapy initiation in cases with mild-to-moderate COVID-19: A personal experience from an attending pharmacist and his resident.

I am a professor and attending pharmacist in the field of pharmaceutical sciences and writer or co-author of at least 5 manuscripts about different aspects of COVID-19. More than 15 months from the first report of COVID-19, over 120 million people all over the world infected by this virus, and more than 2.5 million of them have died. Although different treatment approaches have been proposed, management of the COVID-19 patients is steal remained controversial. In this regard, I want to share my personal experience from the exposure to the coronavirus and the consequence of this infection on my health status. I am a 51 years old male, known case of hypertension, dyslipidemia, and chronic kidney disease. During working hours of colleagues in the Faculty of Pharmacy, I visited one of my colleagues in his office. After leaving the Faculty, my colleague declares that his RT-PCR test of COVID-19 is positive and it took 3 days for me to experience the first sign of the COVID-19 as fever. Many complications have occurred for me during the different stages of COVID-19 infection that I shared and explained in detail with the suggested pharmacotherapies. According to the pathophysiology of COVID-19 infection and my personal experience during COVID-19 infection, I want to emphasize the necessity of early initiation of anti-inflammatory agents including corticosteroids and colchicine in high-risk patients with mild-to-moderate COVID-19 pneumonia who shows respiratory system involvement, in order to prevent progression to the severe and critical stages of this disease.

Still’s disease mimicking sepsis in a young woman. A case report and literature review

Background Adult onset Still’s disease (ASD) is a rare systemic auto-inflammatory condition that often poses a diagnostic dilemma due to nonspecific clinical signs and symptoms. We report a case of ASD that dramatically improved after a short course of steroids. Case presentation A 23-year-old women from Ghana presented with a two-week history of fever, sore throat, right-sided neck swelling and an evanescent, pruritic rash on her extremities. On exam she was febrile to 103 F, tachycardic, tachypneic, had tender, right-sided cervical lymphadenopathy, and diffuse joint tenderness with decreased range of motion. She was admitted to the ICU for possible sepsis and started on broad-spectrum antibiotics. Extensive work-up for possible infectious and auto-immune etiologies, including a bone marrow biopsy was negative. The diagnosis of Still’s disease was made based on the Yamaguchi criteria. The patient was started on methyl-prednisolone and significantly improved within 24 hours. Conclusion Patients presenting with ASD often represent a diagnostic challenge. Clinicians should be aware of this rare disorder, exclude other more frequent diseases and start early anti-inflammatory therapy to avoid poor outcomes.

Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of novel coronavirus infection (COVID-19). Case Series and Study Design: COLchicine versus ruxolitinib and secukinumab in open prospective randomIzed trial (COLORIT)

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

Retinal and brain damage during multiple sclerosis course: inflammatory activity is a key factor in the first 5 years

Understanding of the role of focal inflammation, a treatable feature, on neuro-axonal injury, is paramount to optimize neuroprotective strategy in MS. To quantify the impact of focal inflammatory activity on the rate of neuro-axonal injury over the MS course. We quantified the annualized rates of change in peripapillary retinal nerve fiber layer, ganglion cell plus inner plexiform layer (GCIPL), whole-brain, gray matter and thalamic volumes in patients with and without focal inflammatory activity in 161 patients followed over 5 years. We used mixed models including focal inflammatory activity (the presence of at least one relapse or a new/enlarging T2-FLAIR or gadolinium- enhancing lesion), and its interaction with time adjusted by age, sex, use of disease-modifying therapies and steroids, and prior optic neuritis. The increased rate of neuro-axonal injury during the first five years after onset was more prominent among active patients, as reflected by the changes in GCIPL thickness (p = 0.02), whole brain (p = 0.002) and thalamic volumes (p < 0.001). Thereafter, rates of retinal and brain changes stabilized and were similar in active and stable patients. Focal inflammatory activity is associated with neurodegeneration early in MS which reinforces the use of an early intensive anti-inflammatory therapy to prevent neurodegeneration in MS.

Strong upregulation of inflammatory genes accompanies photoreceptor demise in canine models of retinal degeneration.

We have analyzed the complex pattern of the inflammatory response in early-onset canine models of human retinitis pigmentosa, rcd1, xlpra2 and erd, as well as late-onset xlpra1, in comparative manner. The time course of immune response genes and proteins expression was examined along the timeline of photoreceptors degeneration. Gene expression analysis of the early-onset models prior to and after the peak of photoreceptors death identified the involvement of multiple immune response genes including those encoding constituents of the NLRP3 inflammasome, its substrates, pro-IL1B, pro-IL18, and common components of IL1B, IL18 and TLR4 pathways. Out of two activated caspase-1 cleavage products, IL1B and IL18, only IL1B was detected in rcd1 and xlpra2 while precursor IL18 remained unprocessed in the same protein extract highlighting prominence of IL1B pathway. An overall immune response was most prominent in rcd1 followed by xlpra2 and least prominent in erd. Noticeably, in rcd1 and xlpra2, but not in erd, early induction of the immune response was accompanied by sustained intraretinal migration and activation of retinal microglia. Lastly, delayed activation of the anti-inflammatory factors in all early-onset models was insufficient to counterbalance rapidly progressing inflammation. In contrast to early-onset models, in late-onset xlpra1 retinas a subset of the pro-inflammatory genes was highly upregulated long before any disease-related structural changes occurred, but was counterbalanced by an adequate anti-inflammatory response. Results point out to upregulated immune response accompanying disease progression in animal models of retinal degeneration, and to potential benefits of early anti-inflammatory therapy.

CYCLOSPORIN H: A NOVEL ANTI-INFLAMMATORY THERAPY FOR INFLUENZA FLU PATIENTS

Relatively little is known about the inflammatory mediators and mechanisms that drive the progression of influenza flu infection to cytokine storm, lung dysfunction, organ failure, and ultimately death. Vaccines and antiviral medications cannot control the excessive host inflammatory response associated with severe influenza flu infection. Studies by Elgebaly et al demonstrated the rapid release of a potent inflammatory mediator, recently named Nourin, by local mammalian tissues in response to injury and infection. Nourin is a formyl peptide that acts through the formyl peptide receptor (FPR) on phagocytic leukocytes. As an initial signal in the innate immunity, Nourin stimulates leukocyte chemotaxis, induces acute and chronic inflammation, and stimulates the release of a number of the cytokine storm mediators from monocytes, neutrophils and endothelial cells. Furthermore, Nourin detected in plasma samples from patients with severe influenza infection was much higher compared to moderate influenza. The Nourin antagonist, Cyclosporin H, is a potent anti-inflammatory compound, which acts as a specific competitive antagonist of formyl peptides on the formyl peptide receptor (FPR) on phagocytic: leukocytes. Cyclosporin H completely blocked neutrophil chemotaxis induced by: (a) the standard formyl peptide, f-MLF, (b) the Staphylococcus aureus bacteria-derived formyl peptide Phenol-soluble modulins, such as PSM3a, plus(c) the host-derived Nourin released by: (1) cultured epithelial cells infected with the PR8 HINI influenza virus for 6.to 24 hours, (2),Nourin detected in the serum of mouse model of HINI Swine flu influenza infection for 6 hours , along with (3) Nourin detected in plasma samples collected from severe and moderate influenza pa- tients. Furthermore, in-vivo treatment by Cyclosporin H in the mouse model of HINI Swine flu influenza infection for 5 days markedly reduced lung inflammation and endothelial cell damage. Thus, two clinical applications for Nourin and its antagonist Cyclosporin H are proposed: Diagnostic Application: The blood Nourin test can be used as a key inflammatory biomarker for "early" detection and monitoring of influenza flu patients proceeding to hyperactive inflammation and, thus, permitting early crucial anti-inflammatory therapy. Therapeutic Application: Cyclosporin H will specifically block Nourin as an important initial stimulant of cytokine mediators, and thus can control the development and progression of cytokine storm plus organ inflammation, which usually initiates 3 to 8 days post influenza. Since Cyclosporin H does not target the virus,, it will not develop drug resistance,and will reduce the host uncontrpolled inflammatory response, induced by both new strains of flu viruses and existing viruses with mutations.

AB0294 Comparison between several prediction scores and the new EULAR/ACR criteria for diagnosis and prognosis of rheumatoid arthritis

BackgroundNew ACR/EULAR classification criteria for RA were developed in response to the criticism of existing 1987 ACR criteria due to insufficient sensitivity in early disease. According the new criteria a...