Use Of Anti-inflammatory Therapy Research Articles

Prospects for the use of anti-inflammatory therapy in patients with coronary artery disease

Coronary atherosclerosis is the primary cause of coronary artery disease, one of the world’s greatest causes of death. Inflammation plays a major role in atherosclerosis formation and progression. Cardiovascular disease risk factors such as dyslipidemia, hyperglycemia, smoking, hypertension and others contribute to endothelial injury. This sets off a cascade of inflammatory reactions accompanied by the release of cytokines and other inflammatory mediators, ultimately leading to rupture or erosion of the atherosclerotic plaque and atherothrombosis. Large studies such as CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study); COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low Dose Colchicine 2) demonstrated that the use of anti-inflammatory drugs improves the prognosis of patients with coronary atherosclerosis. At present, the most convincing evidence of the effectiveness of anti-inflammatory therapy was obtained only for colchicine and canakinumab. However, despite these promising results, there are still many issues to be addressed. Firstly, more research is needed to determine the optimal dosage and duration of these drugs. Secondly, the safety of their prolonged use should be carefully assessed, especially in the context of possible side effects. For example, anti-inflammatory drugs can potentially pose infectious risks that require special monitoring and follow-up. The review presents current views on the possibilities immunomodulatory drugs using in the complex treatment of atherosclerosis.

INTRAVITREAL 0.18-mg FLUOCINOLONE ACETONIDE IMPLANT FOR PEDIATRIC UVEITIS.

This study reports the outcomes of the 0.18-mg intravitreal fluocinolone acetonide implant in the treatment of pediatric noninfectious uveitis. A retrospective cohort study was performed on patients under 18 years old who received fluocinolone acetonide implant between June 1, 2020 and March 1, 2023. Data collected included demographics, uveitis diagnosis, use of anti-inflammatory therapy, visual acuity, intraocular pressure, and grading of uveitis activity. Uveitis recurrence was defined as increased inflammation that required additional anti-inflammatory therapy. Eleven eyes from seven patients were included in this study. One patient (one eye) had a diagnosis of immune recovery uveitis and the remaining six patients (10 eyes) had pars planitis. The rate of remaining recurrence-free was 82% at 6 months, 60% at 12 months, and 60% at 24 months. Two of the six phakic eyes at baseline required cataract extraction during follow-up. Two of the four eyes that did not have intraocular pressure-lowering surgery before implantation required surgery in follow-up. The 0.18-mg fluocinolone acetonide implant has a similar efficacy for the treatment of pediatric uveitis, particularly pars planitis, as in the adult population, although with higher rates of ocular hypertension requiring intervention.

Potential and place of efferent therapy in patients with myocardial infarction complicated by cardiogenic shock

Myocardial infarction complicated by cardiogenic shock (MI CS) is the terminal stage of the cardiovascular disease continuum, leading to the death of every second patient in its severe course. Over the past decades, there are no improvement in inhospital mortality rates for MI CS, despite the widespread introduction of early and effective revascularization methods and intensive care techniques. Recently, more and more data have emerged on the significant contribution of the systemic inflammatory response (SIR) to the pathogenesis of acute coronary syndrome and its complications. The characteristics and impact of SIR in MI CS on its course and outcome have not been sufficiently studied. One of the strategies to influence the SIR course, along with the use of anti-inflammatory therapy, is efferent treatment. However, despite all the above-mentioned fundamental prerequisites for the use of an extracorporeal therapy in CS patients, the introduction of these techniques into clinical guidelines and practice requires exploratory and multicenter randomized studies. This review article summarizes modern ideas and characterizes the existing possibilities of using efferent therapy in MI CS.

Unraveling the link between neuropathy target esterase NTE/SWS, lysosomal storage diseases, inflammation, abnormal fatty acid metabolism, and leaky brain barrier.

Mutations in Drosophila Swiss cheese (SWS) gene or its vertebrate orthologue neuropathy target esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.

Inflammation and platelet reactivity during adjunctive colchicine versus aspirin in patients with acute coronary syndrome treated with potent P2Y12 inhibitor.

In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4-1.2] vs. 0.9 [0.6-2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20-0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776). In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

Острая задняя мультифокальная плакоидная пигментная эпителиопатия

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is more common in people of young working age. It manifests itself in the appearance of light foci on the retina, leading to a decrease in visual acuity. The presented clinical cases demonstrate an interdisciplinary approach in the diagnosis and treatment of this disease. In some cases, the disease may occur without reducing visual acuity and be undiagnosed. In the acute stage of APMPPE, the use of anti-inflammatory therapy, including systemic steroids, gives a good clinical effect. Keywords: acute posterior multifocal placoid pigment epitheliopathy, gray-white foci, diagnosis, anti-inflammatory therapy

Кардиоваскулярная и метаболическая коморбидность при ревматических заболеваниях: фокус на гиперурикемию и подагру

Cardiovascular and metabolic comorbidities in patients with rheumatic diseases (RD) determine the risk of adverse outcomes. Gout is one of the diseases which significantly increase the cardiovascular risk (CVR). The authors present a literature review elucidating the prevalence and spectrum of cardiovascular (CVD) and metabolic diseases, as well as the proven CVR factors in persons with RDs, including gout. As demonstrated, the increased CVR amid RDs is caused not only by a higher prevalence of the traditional CVR factors but is also related to multiple specific disease-associated risk factors. Chronic systemic inflammation, the development of internal organ lesions and the long-term use of anti-inflammatory therapy contribute negatively to the overall CVR. Thus, RDs are considered as important CVR re-classifiers and require a compulsory revision of the risk factors. Currently, the national and international guidelines for the CVR prevention in persons with RD have been developed and used in practice. Among RDs, a special place is held by gout which is characterized by common cardiovascular comorbidities and reduced glomerular filtration rate. The recent studies have demonstrated that in the management of patients with hyperuricemia (HU) and gout it is necessary to achieve a sustained target level of uric acid for preventing adverse effects on the organ systems and reducing CVR. Among the recommended therapeutic options for patients with cardiovascular and renal comorbidities, the preference is given to febuxostat, a urate-lowering drug with high activity and proven safety. KEYWORDS: comorbidities, rheumatic diseases, gout, cardiovascular risk, febuxostat. FOR CITATION: Babaeva A.R., Kalinina E.V., Zvonorenko M.S. et al. Cardiovascular and metabolic comorbidities associated with rheumatic diseases: focus on hyperuricemia and gout. Russian Medical Inquiry. 2023;7(3):150–159 (in Russ.). DOI: 10.32364/2587- 6821-2023-7-3-150-159.

Medicine Consumption Reminder and Monitoring Application for Patients with Leprosy Disease

Leprosy or also known as Hansen's disease (HD) or Morbius Hansen's disease (MHD) caused by the bacterium Mycobacterium leprae. The symptoms of leprosy are hardly identified. In fact, some symptoms only can be identified after 20-30 years. Recently, the advent of multidrug therapy (MDT) and the use of anti-inflammatory therapies have given substantial improvements in long-term health outcomes for patients diagnosed with leprosy. However, the medication was a time consuming. Healthy behavior in the management of leprosy treatment requires discipline in taking leprosy medication. On the contrary, poor treatment management will lead to permantent consequnces of disability and deformity. Various Android-based applications have been developed by programmers. Smartphone technology is expected to help patients taking medication in supervising and reminding. In addition, through the cloud based technology the mobile application is expected to be solution as medium of information and communication for every stake holder in dealing with leprosy patients. This research involves a series of software development processes which are divided into several phases. Starting with the identification of the problem, moving on to the design of the application and the API service, to the development and testing of the application using a variety of test scenarios, and concluding with the documentation process. Both the functionality and the design were tested using the User Experience Questionnaire (UEQ) and black-box testing. Based on the outcomes of black box testing, the app's functionality work without any issues. The UEQ results show that novelty (Good), stimulation (Good), efficiency (Good), reliability (Above Average), perspicuity (Above Average), and beauty (Good) are all positive (Above Average). According to the UEQ results, the application received the highest efficiency level rating of 1.75, which indicates that it is regarded as having good consumption efficiency and being usable.

Single Institution Experience of Intravitreal 0.18-mg Fluocinolone Acetonide Implant for Noninfectious Uveitis

To report the outcomes of the 0.18-mg fluocinolone acetonide implant (FAi) in the treatment of noninfectious uveitis. Retrospective cohort study. Patients who received the 0.18-mg FAi for the treatment of noninfectious uveitis affecting the posterior segment (NIU-PS) between July 1, 2019, and August 31, 2021, at the University of Colorado. Patients were excluded if they did not have ≥6 months of follow-up after the placement of the implant. Data including age, race/ethnicity, sex, uveitis diagnosis, history and current use of anti-inflammatory therapy, use of short-acting corticosteroid injections within the 3 months before the 0.18-mg FAi implantation, visual acuity, intraocular pressure (IOP), grading of anterior chamber and vitreous cell, and presence of cystoid macular edema were obtained from the medical charts. Uveitis recurrence was defined as any increased inflammation that required additional anti-inflammatory therapy. Probability of remaining recurrence-free after the placement of the 0.18-mg FAi. Sixty-four eyes from 42 patients were included. The overall probability of remaining recurrence-free was 68.8% at 6 months and 52.6% at the 12-month follow-up. Eyes that remained recurrence-free at 12 months had a younger mean age than eyes that had a recurrence within 12 months (P= 0.02). Eyes that received a short-acting corticosteroid injection before the 0.18-mg FAi were more likely to have a recurrence by 6 months of follow-up than eyes that did not receive a pre-FAi corticosteroid injection (P= 0.05). Initiation or addition of IOP-lowering eyedrops was required in 15.6% of eyes, and 4.7% of eyes required IOP-lowering surgery after 0.18-mg FAi placement. The 0.18-mg FAi appears to be an effective option in the management of NIU-PS, with relativelylow rates of ocular hypertension requiring intervention. The use of short-acting corticosteroid injections before the placement of the 0.18-mg FAi does not seem to improve the effectiveness of the 0.18-mg FAi, although this may be partially because of selection bias. Additional studies are required to determine patients who are the optimal candidates for this therapy.

Systemic Inflammation Is Associated With Future Risk of Fatal Infection: An Observational Cohort Study.

BackgroundMany diseases are associated with chronic inflammation, resulting in widening application of anti-inflammatory therapies. Although they are effective as disease-modifying agents, these anti-inflammatory therapies increase the risk of serious infection; however, it remains unknown whether chronic systemic inflammation per se is also associated with fatal infection.MethodsUsing serum C-reactive protein (CRP) data from 461 052 UK Biobank participants, we defined incidence rate ratios (IRRs) for death from infection, cardiovascular disease, or other causes and adjusted for comorbidities and the use of anti-inflammatory therapies.ResultsSystemic inflammation, defined as CRP ≥2 mg/L, was common in all comorbidities considered. After adjusting for confounding factors, systemic inflammation was associated with a higher IRR point estimate for infection death (1.70; 95% confidence interval [CI], 1.51–1.92) than cardiovascular (1.48; CI, 1.40–1.57) or other death (1.41; CI, 1.37–1.45), although CIs overlapped. C-reactive protein thresholds of ≥5 and ≥10 mg/L yielded similar findings, as did analyses in people with ≥2, but not <2, comorbidities.ConclusionsSystemic inflammation per se identifies people at increased risk of infection death, potentially contributing to the observed risks of anti-inflammatory therapies in clinical trials. In future clinical trials of anti-inflammatory therapies, researchers should carefully consider risks and benefits in target populations, guided by research into mechanisms of infection risk.

ЕВОЛЮЦІЯ РЕКОМЕНДАЦІЙ GINA. ПРАКТИЧНІ АСПЕКТИ ЛІКУВАННЯ ПАЦІЄНТІВ З АСТМОЮ ЧЕРЕЗ ПРИЗМУ КЛІНІЧНИХ ДОСЛІДЖЕНЬ

EVOLUTION OF GINA GUIDELINES. PRACTICAL ASPECTS OF ASTHMA MANAGEMENT THROUGH THE PRISM OF CLINICAL TRIALS S. V. Zaikov, F. T. Bogomolov, G. L. Gumeniuk Abstract Through the 28 years lifetime of GINA (Global Initiative for Asthma) recommendations, there’s been a shift in the paradigm of asthma management. GINA is a Global Strategy of treatment and prophylaxis of asthma, established by National Heart, Lung and Blood Institute in collaboration with National Institute of Health and World Health Organization in 1993. First published in 1995 GINA report has become a widespread consensus, which made a basis for clinical recommendations on asthma worldwide. One can define three major periods in evolution of GINA. The first period covered 1994–2004 years since GINA originated and first edition published until experts have recognized the advantage of inhaled rout of asthma drugs administration. It was proved that in many patients the main goal was establishing asthma control, while combination of inhaled corticosteroid with long-acting beta agonist (ICS/LABA) was a preferred option in moderate persistent asthma. In this period it was recommended to chose an approach to managent of asthma, based on scientific evidence, rather then expert’s opinion. In this regard, a second period (2005–2014 years) should be considered outstanding, due to the change in perception of major goals of asthma management, considering exclusively data from numerous studies. Such concepts as patient-medical personnel partnership, patient’s education, guided self-control and goals of treatment have been introduced. GINA recommends to use asthma control as a major approach to treatment instead of severity of disease. Personalized treatment should be aimed on exacerbation risk reduction. Steps 3-5 of treatment algorithm were modified to include ISC-formoterol for maintenance therapy and relief of symptoms (MART-therapy). Third period of GINA started after SYGMA 1 and 2 studies results became available. It was demonstrated that on-demand symptom-relief use of anti-inflammatory therapy with ICS/formoterol combination was highly effective in mild asthma patients. Use of this combination as rescue medication decreased the risk of exacerbation in comparison with short-acting beta agonist (SABA) and may be used in any variant of asthma. Since GINA 2019 edition SABA became not the only one available option even for the mildest forms of asthma. Eventually, in 2021 the culmination of GINA evolution occurred: major algorithm of asthma management has been divided in two tracks: preferred (Track 1) therapy with ICS/formoterol and alternative (track 2) therapy with SABA as rescue medication. The authors of this article review in details the periods of GINA evolution, resulted in dividing asthma management into two tracks, which provide personalized treatment strategy considering all patient’s needs and characteristics such as fast relief of symptoms, decreased risk of exacerbation and establishing asthma control. Key words: asthma, GINA, evolution of treatment approaches. Ukr. Pulmonol. J. 2022;30(1):6–14

Abstract 11313: Pericarditis Recurrence After Initial Uncomplicated Clinical Course

Introduction: Acute pericarditis is an inflammatory disease associated with a non-negligible risk of acute complications and future recurrence. The exact incidence of pericarditis recurrence in patients with a first uncomplicated clinical course is, however, unknown. Objectives: We sought to evaluate the incidence and clinical predictors of recurrence after a first episode of acute uncomplicated pericarditis in a large urban hospital in the USA. Methods: We conducted a retrospective review, through electronic health records, to complete a database that includes patients admitted with a first episode of acute pericarditis (according to ESC criteria) and then selected only those with uncomplicated course (without in-hospital death, large pericardial effusion [&gt;20 mm] or tamponade, constriction, or failure of treatment) at the VCU Medical Center (Richmond, VA) between 2009 and 2018. Results: A total of 240 patients met acute pericarditis criteria: 174 (72%) patients had an uncomplicated course (median age was 50 [interquartile range 34 to 62] years, 45% females, 51% Black). Pericarditis was considered idiopathic in 89 patients (51%). During a median follow-up time of 184 [17- 434] days, 23 (13%) patients experienced at least one episode of recurrent pericarditis. When compared with those without recurrence, patients with recurrent pericarditis were more frequently females (15 [65%] vs 63 [42%], p=0.035) and had a higher prevalence of subacute/delayed presentation (defined as symptoms over several days without a clear-cut acute onset) (3 [13%] vs 1 [0.7%], p=0.008). There were no other clinical (including the use of anti-inflammatory therapies and pericarditis etiology) or laboratory differences between those with and without pericarditis recurrence at follow-up. At multivariate logistic regression analysis only subacute presentation remained predictor of recurrence at follow-up (odds ratio 20, 95% confidence interval [1.81-198.11], p=0.014). Conclusions: Approximately one every six patients with an acute pericarditis experience a recurrence over a 6-month median follow-up despite an initial uncomplicated course. Subjects with subacute presentation were at significantly higher risk of recurrence.

UNEXPECTED OPPORTUNISTIC INFECTION IN PATIENT WITH SEVERE COVID-19 PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The pathogenesis of the novel coronavirus, Covid-19, was characterized by an overdrive of the immune system that lead to some patients to a life-threatening cytokine storm with severe lung inflammation and multiorgan failure. Considering this pathogenic pathway, the use of high dose systemic steroids, and other immunomodulatory therapy was part of the main therapy. As management evolves, complications have risen, including cardiac, thromboembolic, neurologic and secondary infections. Multiple clinical reports have described complications with bacteria, and fungal infections in different organ systems, most commonly the respiratory track. However, systemic and multiorgan infections have been reported due to severe immunosuppression after viral infection and the use of anti-inflammatory therapy. CASE PRESENTATION: We present the case of an 86-year-old male with a past medical history of benign prostate hypertrophy, hyperlipidemia and hypertension who developed respiratory failure due to severe COVID-19 pneumonia, managed with antiviral therapy and high dose dexamethasone. After initial improvement from the respiratory standpoint, the patient developed persistent fungemia with Candida parapsilosis. There was no evidence of endocarditis. The patient presented with persistent altered mental status after cessation of sedation. Brain imaging revealed a right posterior parietal parafalcine hematoma with surrounding vasogenic edema. Angiogram revealed a saccular aneurysm measuring approximately 5.7 mm in largest dimension located at midline posterior frontal in location in relation to pericallosal arteries. Cerebral arterial aneurysm secondary to systemic fungal infection, knowns as mycotic aneurysms, have been reported in medical literature. DISCUSSION: Aneurysms are an abnormal arterial focal dilation which can become infected, but also aneurysmal degeneration of the arterial wall can occur due to bacteremia or a septic embolus;as seen in mycotic aneurisms. Despite its name, most mycotic aneurysms are caused by bacteria from associated endocarditis. This is a serious complication associated to an elevated morbidity and mortality. Several risk factors predispose to infected aneurysm, these include arterial injury, infection, immunocompromised status, atherosclerosis and pre-existing aneurysms. Fungal infections tend to be rare but may occur in immune suppressed patients or as sequelae of treatment of disseminated fungal disease. CONCLUSIONS: This is an unexpected complication of immunosuppression with systemic steroids in management of COVID-19 pneumonia. Treatment with systemic steroid and thromboembolic complication prevention have helped improve COVID-19 pneumonia patient prognosis, however physicians should be careful as it predisposes patients, especially those with advanced age, to opportunistic infections in unexpected organ and settings. REFERENCE #1: WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JPT, Horby P, Juni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Moller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341. doi: 10.1001/jama.2020.17023. PMID: 32876694;PMCID: PMC7489434. REFERENCE #2: Wu FZ, Lai PH. Evolution and regression of intracranial infectious aneurysm diagnosed by brain computed tomographic angiography. Arch Neurol. 2010 Sep;67(9):1147. doi: 10.1001/archneurol.2010.216. PMID: 20837863. REFERENCE #3: World Health Organization. Corticosteroids for COVID-19: Living guidance. https://www.who.int/publications/i/item/WHO-2019-nCoV-Cor icosteroids-2020.1 DISCLOSURES: No relevant relationships by Onix Cantres-Fonseca, source=Web Response No relevant relationships by Porfirio Diaz-Rodriguez, source=Web Response No relevant relationships by Hector Nieves, source=Web Response No relevant relationships by Luis Vazquez, source=Web Response

Effect of anti-inflammatory therapy on major cardiovascular events in patients with diabetes: A meta-analysis

BackgroundIn patients with coronary artery disease anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events. The effect of this intervention in the population with type 2 diabetes mellitus (T2DM) is poorly explored. The main objective of this study was to evaluate the effect of anti-inflammatory therapy on the incidence of major cardiovascular events (MACE) in patients with T2DM. MethodsA meta-analysis of randomized studies that evaluated the use of anti-inflammatory therapy in patients with T2DM and reported MACE was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. A fixed or random effects models were used. ResultsFive studies were selected for the analysis (2075 subjects in the anti-inflammatory therapy arm and 2490 patients in the placebo/control arm). All studies included patients with T2DM and history of coronary artery disease. Four studies evaluated the use of colchicine and one of them canakinumab. The use of anti-inflammatory therapy was associated with a lower risk of MACE (HR: 0.80; 95% CI, 0.69–0.93; I2 = 24%). The sensitivity analysis shows that the results are robust. ConclusionThis meta-analysis demonstrated that the use of anti-inflammatory therapy in patients with T2DM and atherosclerotic cardiovascular disease was associated with reduced risk of MACE. These results suggest the need to consider the inflammatory pathway as a potential therapeutic target in patients with T2DM.

Sarcoidosis

Sarcoidosis is a systemic disease characterized by the presence of noncaseating granulomas, which accumulate in affected organs. The incidence, organ involvement, and disease severity depend on environmental exposures and host factors. The cause of sarcoidosis remains unknown. Any organ can be affected; however, involvement of the lung, heart, and nervous system contributes most to morbidity and mortality. This review discusses the epidemiology, etiology, genetics, pathogenesis, diagnosis (including clinical manifestations), differential diagnosis, management, complications, and prognosis of sarcoidosis. Figures depict the pathogenesis of sarcoidosis, radiographic stages of sarcoidosis, contrast-enhanced magnetic resonance imaging of a patient with neurosarcoidosis, noncaseating granuloma from a tissue biopsy of a patient with sarcoidosis, various manifestations of sarcoidosis, approach to the use of anti-inflammatory therapy for sarcoidosis, and an algorithm for symptomatic disease. This review contains 7 highly rendered figures, 7 tables, and 127 references Keywords: cardiac sarcoidosis, hilar lymphadenopathy, Löfgren syndrome, neurosarcoidosis, noncaseating granuloma, sarcoidosis, uveitis

Sarcoidosis

Sarcoidosis is a systemic disease characterized by the presence of noncaseating granulomas, which accumulate in affected organs. The incidence, organ involvement, and disease severity depend on environmental exposures and host factors. The cause of sarcoidosis remains unknown. Any organ can be affected; however, involvement of the lung, heart, and nervous system contributes most to morbidity and mortality. This review discusses the epidemiology, etiology, genetics, pathogenesis, diagnosis (including clinical manifestations), differential diagnosis, management, complications, and prognosis of sarcoidosis. Figures depict the pathogenesis of sarcoidosis, radiographic stages of sarcoidosis, contrast-enhanced magnetic resonance imaging of a patient with neurosarcoidosis, noncaseating granuloma from a tissue biopsy of a patient with sarcoidosis, various manifestations of sarcoidosis, approach to the use of anti-inflammatory therapy for sarcoidosis, and an algorithm for symptomatic disease. This review contains 7 highly rendered figures, 3 tables, and 126 references Keywords: cardiac sarcoidosis, hilar lymphadenopathy, Löfgren syndrome, neurosarcoidosis, noncaseating granuloma, sarcoidosis, uveitis

Fenspiride use in acute respiratory infections in children

Acute respiratory infections are the most common pathology in childhood, representing not only a medical but also a socio-economic problem. Numerous studies on the use of anti-inflammatory therapy in ARI have shown high efficacy and safety profile of fenspiride. The combination of anti-inflammatory, antiallergic, and antispasmodic properties ensures the success of fenspiride in the treatment of acute respiratory diseases in children. Fenspiride reduces symptoms of ARI, accelerates recovery, reduces the need for additional prescription of other drugs.

CD4+ T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during Cryptococcus neoformans Meningoencephalitis.

ABSTRACTCryptococcus neoformans is a major fungal pathogen that disseminates to the central nervous system (CNS) to cause fatal meningoencephalitis, but little is known about immune responses within this immune-privileged site. CD4+ T cells have demonstrated roles in anticryptococcal defenses, but increasing evidence suggests that they may contribute to clinical deterioration and pathology in both HIV-positive (HIV+) and non-HIV patients who develop immune reconstitution inflammatory syndrome (IRIS) and post-infectious inflammatory response syndrome (PIIRS), respectively. Here we report a novel murine model of cryptococcal meningoencephalitis and a potential damaging role of T cells in disseminated cryptococcal CNS infection. In this model, fungal burdens plateaued in the infected brain by day 7 postinfection, but activation of microglia and accumulation of CD45hi leukocytes was significantly delayed relative to fungal growth and did not peak until day 21. The inflammatory leukocyte infiltrate consisted predominantly of gamma interferon (IFN-γ)-producing CD4+ T cells, conventionally believed to promote fungal clearance and recovery. However, more than 50% of mice succumbed to infection and neurological dysfunction between days 21 and 35 despite a 100-fold reduction in fungal burdens. Depletion of CD4+ cells significantly impaired IFN-γ production, CD8+ T cell and myeloid cell accumulation, and fungal clearance from the CNS but prevented the development of clinical symptoms and mortality. These findings conclusively demonstrate that although CD4+ T cells are necessary to control fungal growth, they can also promote significant immunopathology and mortality during CNS infection. The results from this model may provide important guidance for development and use of anti-inflammatory therapies to minimize CNS injury in patients with severe cryptococcal infections.

Inflammation and myointimal hyperplasia. Correlation with hemodynamic forces

ObjectivesThe aim of our study was to correlate flow dynamics and the release of inflammatory cytokines Interleukin 1, 2, 6, TNF (Tumour Necrosis Factor) alfa, both in vitro and in vivo. Materials and methodsEndothelial cells were exposed to laminar flow (6dyne/cm2) in an in vitro circulatory system and the release of Interleukin 1, 2, 6 and TNF alfa was quantified by ELISA. Interleukin 1, 2, 6 and TNF alfa release was also assessed in vein grafts implanted in the arterial circulation of Lewis rats. Arterial vein grafts were explanted at different time intervals from 3days to 12weeks after surgery. Vein grafts implanted in the arterial circulation for 4weeks, were re implanted in the venous circulation of syngenic Lewis rats, and the release of Interleukin 1, 2, 6 and TNF alfa, was assessed in an organ culture.Six vein grafts (4 occluded, 2 patent) implanted in humans as femorodistal bypass were examined for the presence of myointimal hyperplasia and perigraft inflammatory cells. ResultsIn vitro, endothelial cells exposed to laminar flow released an increased amount of Interleukin 1, 2, 6 and TNF alfa in comparison to endothelial cells not exposed to flow.In experimental vein grafts implanted in the arterial circulation there was an increased release of inflammatory cytokines associated to inflammatory changes in the adventitia. Once the vein grafts were re implanted in the venous circulation, the release of these cytokines diminished, while the inflammatory changes in the adventitia regressed. ConclusionsIncreased shear stress induces release of cytokines and inflammatory changes in the adventitia. These inflammatory changes can contribute to plaque progression and to un stable plaque. These findings support the use of anti-inflammatory therapy in patients prone to develop atherosclerosis and in those who had arterial reconstructive surgery.

New molecular targets for the treatment of sarcoidosis.

Sarcoidosis is a chronic granulomatous disease typically affecting the lung, lymph nodes, and other organ systems. Evidence suggests that the morbidity and mortality rates for sarcoidosis in the USA are rising, despite widespread use of anti-inflammatory therapies. In this review, we survey new therapies that target specific inflammatory pathways in other diseases (such as rheumatoid arthritis, Crohn's disease, and psoriasis) that are similar to pathways relevant to sarcoidosis immunopathogenesis, and therefore, represent potentially new sarcoidosis therapies. Immunopathogenesis of sarcoidosis has been well elucidated over the past few years. There is abundant evidence for T-cell activation in sarcoidosis leading to activation of both Th1 and Th17 inflammatory cascades. Therapies targeting T-cell activation, Th1 pathways (such as the interleukin-6 inhibitors), Th17 pathway mediators, and others have been Food and Drug Administration approved or under investigation to treat a variety of autoimmune inflammatory diseases, but have not been studied in sarcoidosis. Targeting the p38 mitogen-activated protein kinases and the ubiquitine proteasome system with new agents may also represent a novel therapeutic option for patients with sarcoidosis. Rising morbidity and mortality rates for patients with sarcoidosis strongly support the need to develop more effective anti-inflammatory therapies to treat chronic disease.