Anti-inflammatory Therapy In Patients Research Articles

Retracted: Red Cell Distribution Width: A Clinical Indicator to Assess Severity and Guide Anti-Inflammatory Therapy in Patients with Knee Osteoarthritis

Retracted: Red Cell Distribution Width: A Clinical Indicator to Assess Severity and Guide Anti-Inflammatory Therapy in Patients with Knee Osteoarthritis

465-P: Anti-inflammatory Therapies in Patients with Established Cardiovascular Disease or High Cardiovascular Risks

Background: To evaluate the association between anti-inflammatory therapies and the incidence of cardiovascular events in patients with established cardiovascular disease (CVD) or high cardiovascular risks. Methods: Literature retrieval was conducted in Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov website from the inception to July 2022. Randomized controlled trials compared anti-inflammatory therapies with placebo in patients with established CVD or high cardiovascular risks were included. The results of the meta-analysis were computed as the odds ratio (OR) with 95% confidence interval (CI). Results: Compared with placebo, anti-inflammatory therapies were associated with decreased incidence of myocardial infarction (MI) (OR=0.93, 95%CI, 0.87 to 0.98), which was mainly driven by therapies targeting central IL-6 signaling pathway (OR=0.84, 95%CI, 0.76 to 0.94). IL-1 inhibitors treatment was associated with reduced risks of heart failure (OR=0.32, 95%CI, 0.14 to 0.76) while lower incidence of stroke was observed in patients with colchicine treatment (OR=0.46, 95%CI, 0.28 to 0.77). MI events were less frequent in patients over 65 years old (OR=0.90, 95%CI, 0.82 to 0.98) or with follow-up duration over 1 year (OR=0.90, 95%CI, 0.84 to 0.96)when comparing anti-inflammatory therapies with placebo. Conclusion: Anti-inflammatory therapies, especially those targeting central IL-6 signaling pathway may serve as promising treating strategies to ameliorate the risk of MI. Meanwhile, IL-1 inhibitor and colchicine were associated with decreased risks of heart failure and stroke respectively. MI risk reductions by anti-inflammatory therapies seem to be more prominent in patients who were elderly and with long follow-up duration. Disclosure C.Lin: None. Z.Li: None. X.Cai: None. L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. Funding National Natural Science Foundation of China (81970698, 81970708); Beijing Natural Science Foundation (7202216)

InflammamiR-146a and -155 Plasma Levels are Associated with Clinical Efficacy of Risankizumab Treatment in Psoriatic Patients: Pilot Study.

The key role of microRNAs (miRNAs) in the pathogenesis of psoriasis has been extensively discussed in the literature. Increasing evidence suggests that the analysis of miRNA levels may constitute an innovative approach for exploring the clinical efficacy of anti-inflammatory therapies in patients with psoriasis. However, so far there have been no published studies evaluating the effects of modulating circulating miRNAs and the efficacy of anti-interleukin-23 (anti-IL-23) therapy. The main objective of the present was to evaluate the diagnostic/prognostic relevance of the levels of five circulating candidate miRNAs (miR-21, miR-146a, miR-155, miR-210, miR-378) in psoriatic patients treated with the anti-IL-23 drug risankizumab. A total of eight psoriatic participants were recruited consecutively from January 2021 to July 2021 at the Dermatology Clinic of Università Politecnica delle Marche (UNIVPM) "Ospedali Riuniti" of Marche. Data on anamnestic, clinical and miRNA evaluations before the initiation of risankizumab therapy and after 1year (January 2021-July 2022) of risankizumab therapy were available for all patients. A significant reduction in the signs and symptoms in patients treated with risankizumab was observed after 1year of treatment, suggesting that the drug is effective for treating psoriasis in a context of real-life clinical evaluation. Plasma levels of the two prototypical inflammamiRs, miR-146a and miR-155, were significantly reduced after 1year of risankizumab therapy. Also, in patients before treatment, a significant positive correlation was found between circulating levels of miR-210 and miR-378 and disease severity scores. Our results reinforce the notion that specific circulating miRNAs could have clinical relevance as diagnostic/prognostic biomarkers of psoriatic disease and suggest the potential relevance of these miRNAs as biomarkers of treatment response.

Optical spectral transmission to assess glucocorticoid therapy response in patients with arthritis: a longitudinal follow-up comparison with joint ultrasound

BackgroundOptical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up.Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers.Methods1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses.ResultsOST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83–0.94) and after GC=0.811(95%CI=0.74–0.881); p<0.001]. Furthermore, OST correlated significantly with all examined sonographic activity scores (all; p<0.001) and with swollen joint counts (p<0.01).ConclusionsOST was able to assess response to therapy in a similar way to joint US and correlated significantly with arthritis activity markers. Therefore, OST has proved to be a valuable tool to assist disease activity monitoring in the examined cohort.Trial registrationGerman Registry of Clinical Trials, DRKS00016752

Effects of anti-inflammatory therapies on glycemic control in type 2 diabetes mellitus.

The overall evidence base of anti-inflammatory therapies in patients with type 2 diabetes mellitus (T2DM) has not been systematically evaluated. The purpose of this study was to assess the effects of anti-inflammatory therapies on glycemic control in patients with T2DM. PubMed, Embase, Web of Science, and Cochrane Library were searched up to 21 September 2022 for randomized controlled trials (RCTs) with anti-inflammatory therapies targeting the proinflammatory cytokines, cytokine receptors, and inflammation-associated nuclear transcription factors in the pathogenic processes of diabetes, such as interleukin-1β (IL-1β), interleukin-1β receptor (IL-1βR), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). We synthesized data using mean difference (MD) and 95% confidence interval (CI). Heterogeneity between studies was assessed by I2 tests. Sensitivity and subgroup analyses were also conducted. We included 16 RCTs comprising 3729 subjects in the meta-analyses. Anti-inflammatory therapies can significantly reduce the level of fasting plasma glucose (FPG) (MD = - 10.04; 95% CI: -17.69, - 2.40; P = 0.01), glycated haemoglobin (HbA1c) (MD = - 0.37; 95% CI: - 0.51, - 0.23; P < 0.00001), and C-reactive protein (CRP) (MD = - 1.05; 95% CI: - 1.50, - 0.60; P < 0.00001) compared with control, and therapies targeting IL-1β in combination with TNF-α have better effects on T2DM than targeting IL-1β or TNF-α alone. Subgroup analyses suggested that patients with short duration of T2DM may benefit more from anti-inflammatory therapies. Our meta-analyses indicate that anti-inflammatory therapies targeting the pathogenic processes of diabetes can significantly reduce the level of FPG, HbA1c, and CRP in patients with T2DM.

Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).

Aim To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration &gt;60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever &gt;37.5 °C, persistent cough, shortness of breath with inspiratory rate &gt;20 per min or blood saturation with oxygen &lt;94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.

Anti-inflammatory therapies for cardiovascular diseases: novel evidence, clinical implications, and future perspectives

Inflammation plays an important role in cardiovascular disease. Growing evidence suggests a profound involvement of the inflammatory response in the development and progression of atherosclerosis and its complications. In patients with atherosclerotic cardiovascular disease (ASCVD), residual cardiovascular risk often remains high despite optimal medical therapy and the achievement of the therapeutic targets recommended by current guidelines. Among the multiple components of residual risk, residual inflammatory risk, assessed by plasma levels of high-sensitivity C-reactive protein, has shown a strong association with the incidence of cardiovascular events. Recent studies suggest that therapeutic modulation of inflammation, particularly the interleukin (IL)-1/IL-6 pathway, is a promising strategy for the prevention and treatment of cardiovascular and kidney diseases. This review aims to discuss pragmatically the interaction between inflammation and ASCVD, describe current evidence on anti-inflammatory therapies in patients with cardiovascular and renal diseases, and outline the potential implications of these new therapeutic approaches in contemporary and future practice.

Interaction of inherited genetic variants in the NLRP3 inflammasome/IL-6 pathway with acquired clonal hematopoiesis to modulate mortality risk in patients with HFrEF

Abstract Aims Clonal hematopoiesis (CH), defined as the presence of an expanded somatic blood cell clone due to acquired mutations in leukemia driver genes, was shown to be associated with increased mortality in patients with chronic ischemic heart failure with reduced ejection fraction (HFrEF). Mechanistically, circulating monocytes of mutation carriers display increased expression of proinflammatory genes involved in inflammasome and IL-6 signaling. Inherited single nucleotide variants (SNPs) in the IL-6 pathway are well known to affect inflammatory activation. Therefore, we investigated whether known SNPs in genes encoding for components of the inflammasome/IL-6 signaling pathway modulate fatal outcomes in HFrEF patients with CH. Methods and results In a total of 446 patients with chronic HFrEF, peripheral blood or bone marrow mononuclear cells were analyzed for the CH driver mutations DNMT3A and TET2 as well as 40 preselected SNPs affecting genes in the NLRP3 inflammasome/IL-6 signaling pathway. The 103 patients carrying a CH driver mutation demonstrated significantly increased mortality compared to the 343 patients without CH mutations (25,24% vs 13.99% at five years; p=0.0064). We identified three commonly occurring variants known to disrupt IL-6 signaling (rs2228145, rs4129267 and rs4537545) which are in strong linkage disequilibrium and present in more than 50% of CH carriers. As illustrated in Figure 1A, harboring one of those SNPs abrogated the increased mortality risk in patients with HFrEF and CH (p≤0.05 for each SNP). On the contrary, three different SNPs namely rs2250417, which is associated with increased IL-18 levels as well as rs4722172 and rs4845625, which are known to activate IL-6 signaling, were identified to mediate fatal outcomes in patients with HFrEF and CH (p&amp;lt;0.05 for each; Figure 1B). None of the assessed SNPs influenced outcomes in patients without CH. Single cell RNA-sequencing of circulating monocytes of patients with HFrEF revealed increased inflammatory signaling in DNMT3A mutation carriers without protective SNPs with genes upregulated in pathways such as “Cellular response to stress” (FDR −log 24.3), “Regulation of cell activation” (FDR −log 22.7) or “Cytokine signaling in the immune system” (FDR −log18.2). Conclusion Among CHIP carriers with HFrEF, inherited variants in loci encoding for genes involved in inflammatory signaling associate with mortality. These data not only provide mechanistic insights into inflammatory mechanisms contributing to fatal outcome of HFrEF in CH carriers but may also inform trials evaluating precision-targeted anti-inflammatory therapy in patients with DNMT3A and TET2 mutations and chronic HFrEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center of Cardiovascular Research;Cardiopulmonary Institute, Frankfurt, Germany

A method for predicting the effectiveness of glucocorticoid therapy in patients with moderate COVID-19 based on simple clinical and laboratory data

Background: In patients hospitalized with coronavirus infection (COVID-19), methods for predicting the effectiveness of anti-inflammatory therapy have important practical implications for optimizing treatment and outcomes. To date, a number of indicators of COVID-19 patients (age, comorbidities, laboratory criteria for the intensity of inflammation) have been identified that indicate a high probability of a severe course and a risk of an adverse outcome. However, the problem of predicting the effectiveness of anti-inflammatory therapy in patients with moderate COVID-19 is not well understood.&#x0D; Aims: to develop a predictive model to determine the effectiveness/failure of glucocorticosteroid (GCS) monotherapy in patients with moderate COVID-19.&#x0D; Methods. Retrospective analysis of electronic medical record data of all patients admitted consecutively from October 1, 2020 to January 31, 2021. The study included 71 patients with a probable (clinically confirmed) and confirmed (laboratory) case of COVID-19 of moderate course, with characteristic changes in the lungs according to computed tomography of the chest organs (CT-CCT). Given the severity of the course, all patients in this sample were prescribed GCS in accordance with the current version of the Interim Guidelines of the Ministry of Health of the Russian Federation.&#x0D; Results. A total of 71 patients were studied, 53 (74.7%) of them did not require an escalation of anti-inflammatory therapy, which was regarded as an effective use of corticosteroids in the form of monotherapy (group 1). In the remaining 18 patients, the use of corticosteroids for an average of 5.5 (from 3 to 6) days did not have a definite clinical effect and required the additional use of monoclonal antibodies (MCA) to interleukin-6 (IL-6) or to its receptor (group 2). Using logistic regression analysis and ROC analysis, a mathematical model was developed and evaluated to predict the outcome of anti-inflammatory corticosteroid therapy in patients with moderate COVID-19. As risk factors, indicators were selected that had significant differences in the studied groups before the appointment of GCS: the number of lymphocytes, platelets and body temperature.The quality of the constructed model is assessed as very good, the optimal cutoff point is 0.697. The sensitivity index of the model is 81.1%, the specificity index is 72.2%.&#x0D; Conclusions. The mathematical model makes it possible to predict the effectiveness of GCS therapy according to the number of lymphocytes, platelets and body temperature. The mathematical model is adequate, has a high sensitivity and specificity.

Phenomenon of reduced blood oxygen saturation in COVID-19 patients after the use of monoclonal antibodies

Monoclonal antibodies IL-6 inhibitors (olokizumab) and IL-6 receptor inhibitors (tocylisumab, levilimab) are most widely used for proactive anti-inflammatory therapy in patients with COVID-19. A decrease in blood oxygen saturation after 12–72 hours of anticytokine therapy has been recently observed in some patients treated with MAB. Unfortunately, little attention is paid to this problem. As a rule, the deterioration of the patient’s condition is attributed to the natural course of the disease. The purpose of the study is to identify predictors of reduced blood oxygen saturation against the administration of IL-6 inhibitors and its receptors in patients with new coronavirus infection (COVID-19). Material and methods. The study included 54 patients with COVID-19 who were treated permanently between 2020 and 2021 and were given IL-6 inhibitors or receptors (tocilizumab, olokizumab or levililmab). The results of clinical examination, laboratory and instrumental research were evaluated. Results and conclusions. Clinical-laboratory parameters reliably correlated with decreased blood oxygen saturation against the administration of IL-6 inhibitors and its receptors are as follows: administration of MAB after 2 days of inpatient treatment (OR = 3.52; 95% CI 1.026–12.073; p = 0.04), the presence of hypertonic disease in combination with ischemic heart disease or obesity (OR = 4.0; 95% CI 1.0–16.925; p = 0.049 and OR = 7.353; 95% CI 1.429–37.848; p = 0.009 respectively), increase in the number of monocytes greater than 0.6 × 109/l (OR = 4.929; 95% CI 1.327–18.307; p = 0.014), the decrease of albumin less than 35.1 g/l (OR = 30.0; 95% CI 1.410–638.186; p = 0.033), glucose of venous blood 5.9 mmol/l and above (OR = 11.556; 95% CI 1.223–109.19; p = 0.018). Based on the data obtained in this study, it is recommended to evaluate the predictors listed above before conducting targeted anti-inflammatory therapy, and, if they are available, to dynamically monitor patients for reduced blood oxygen saturation.

Resolvin D1 Inhibits Corneal Inflammation in Staphylococcus Aureus Keratitis

ABSTRACT Purpose To investigate the role of lipid mediator, resolvin D1 (RvD1), in corneal inflammation. Methods The anti-inflammatory effect of RvD1 on stimulated human corneal epithelial cells (HCECs) was assessed. C57BL/6 mice corneas were abraded and treated with RvD1 after stimulation with Staphylococcus aureus. Cytokine levels in the corneas, cervical drainage lymph nodes (DLNs), and spleens were measured. Anterior segment photography and optical coherence tomography quantified the changes in corneal thickness and haziness. Neutrophil infiltration in the cornea was examined by haematoxylin and eosin (H&E) staining and immunohistochemistry. Results RvD1 significantly inhibited cytokine production in HCECs and mouse corneas, cervical DLNs, and spleens while stimulating interleukin-10 (IL-10) production. Corneal opacity development, thickening, and neutrophil infiltration significantly reduced in response to RvD1 stimulation in the S. aureus-infected mice corneas. Conclusion RvD1 inhibited S. aureus-induced corneal inflammation. These results potentiate RvD1 as an anti-inflammatory therapy for patients with corneal inflammation induced by bacterial keratitis.

Safety and efficacy of anti-inflammatory therapy in patients with coronary artery disease: a systematic review and meta-analysis

BackgroundThe inflammation hypothesis of atherosclerosis has been put forward for more than 20 years. Although many animal experiments have suggested that anti-inflammatory therapy can inhibit the atherosclerotic process, the efficacy of anti-inflammatory therapy for patients with coronary artery disease (CAD) is still controversial. Therefore, this study aims to evaluate the safety and efficacy of anti-inflammatory drugs in patients with CAD.MethodWe conducted this systematic review and meta-analysis of randomized controlled trials by searching PubMed, EMBASE, web of science, and Cochrane Library database. The primary outcome was a composite outcome of cardiovascular death, myocardial infarction (MI), or stroke. The secondary outcomes included individual MI, coronary revascularization, cardiovascular death, all-cause death, and stroke. The relative risk (RR) and 95% confidence intervals (CI) for outcome events were calculated by the fixed effects model, and trial sequential analysis was applied to assess the results.ResultA total of ten randomized controlled trials and 60,782 patients with CAD was included. Compared with patients receiving placebo, anti-inflammatory therapy significantly reduced the incidence of the primary outcome in patients with CAD (RR 0.93, 0.89–0.98, P = 0.007). In addition, the anti-inflammatory therapy can also reduce the risk of MI (RR 0.90, 0.84–0.96, P = 0.002) and coronary revascularization (RR 0.74, 0.66–0.84, P < 0.00001) remarkably. However, there was no significant difference in the incidence of cardiovascular death (RR 0.94, 0.86–1.02, P = 0.14), all-cause death (RR 1.00, 0.94–1.07, P = 0.98) and stroke (RR 0.96, 0.85–1.09, P = 0.51) between two groups.ConclusionsAnti-inflammatory therapy can reduce the incidence of the primary outcome in patients with CAD, especially the risk of MI and coronary revascularization. However, anti-inflammatory therapy increases the risk of infection. (Registered by PROSPERO, CRD 420212291032).

Changes of Optical Coherence Tomography Biomarkers in Macular Edema Secondary to Retinal Vein Occlusion After Anti-VEGF and Anti-Inflammatory Therapies.

PurposeThis study aimed to assess the short-term changes of macular microstructures following anti-VEGF and anti-inflammatory therapies in patients with macular edema secondary to retinal vein occlusion (RVO-ME).Patients and MethodsIn this retrospective study, 70 eyes of 70 patients with RVO-ME were divided into the anti-VEGF (Group A, 35 eyes) and anti-inflammatory (Group B, 35 eyes) treatment groups. All patients underwent best-corrected visual acuity (BCVA) assessment, intraocular pressure (IOP) assessment, slit lamp, fundus fluorescein angiography (FA), scanning laser ophthalmoscopy (SLO), and spectral-domain optical coherence tomography (SD-OCT). Group A received intravitreal injection of 0.05 mL anti-VEGF antibodies (Lucentis® or Aflibercept®) monthly for 3 consecutive months, while Group B received 0.7 mg dexamethasone (Ozurdex®) single intravitreal injection. BCVA and SD-OCT biomarkers were recorded at baseline and 3 months after the first injection. Changes of BCVA and SD-OCT biomarkers following these treatments were compared between the two groups.ResultsBCVA and SD-OCT biomarkers, except choroidal thickness, in both groups were significantly improved after treatment (all P < 0.01). At 3 months, the height of serous retinal detachment (SRD) was markedly lower (P = 0.006), with significantly less hyperreflective dots (HRD, P = 0.037) in Group B compared with Group A. Other SD-OCT biomarkers and BCVA were not significantly different between the two groups (all P > 0.05).ConclusionAnti-VEGF and anti-inflammatory therapies are both effective in RVO-ME, with improvement in BCVA and SD-OCT biomarkers. Anti-inflammatory therapy may be more effective than anti-VEGF therapy in SRD and HRD resolution.

Red Cell Distribution Width: A Clinical Indicator to Assess Severity and Guide Anti-Inflammatory Therapy in Patients with Knee Osteoarthritis

To explore the influence factors of the red cell distribution width (RDW) level in knee osteoarthritis (KOA) patients, the difference in RDW before and after total knee arthroplasty (TKA), and further explain the clinical value of the RDW level in KOA patients. Information of 195 patients with KOA and 43 patients with meniscus injuries undergoing surgical treatment in the Surgery Department of Joint and Microsurgery Repair and the Surgery Department of Sports Trauma and Joint Arthroscopy of the First Affiliated Hospital of Anhui Medical University from June 1, 2020, to December 1, 2020, were collected. All included patients’ gender, age, height, medical history, blood lipid, erythrocyte sedimentation rate (ESR), CRP, RDW, anteroposterior and lateral X-ray images of the knee joint, and magnetic resonance imaging (MRI) of the knee joint were recorded. The difference in RDW of KOA patients with different severities before and after unilateral TKA surgery was compared, and the difference between KOA patients and patients with only meniscus injury was also compared for further analysis of the influence factors of the RDW level in moderate-severe KOA patients. Among moderate-severe KOA patients with different imaging severities, the RDW level was significantly different (P = 0.022). There was no statistical difference between the groups with and without the TKA history. The RDW level was higher in KOA patients than in patients with only meniscus injuries, and the difference was statistically significant P &lt; 0.05 . To some extent, the RDW level could be taken as a predictor for the severity of moderate-severe KOA patients, and its elevation was primarily related to chondritis and synovitis caused by KOA, so it was suggested that the patients receive adjuvant anti-inflammation therapy after TKA surgery.

Sensitization to Malassezia Sympodialis is Associated with Low Efficacy of Local Anti-inflammatory Therapy in Patients with Contact Dermatitis

IgE sensitization to Malassezia Sympodialis can lead to severe exacerbations in patients with atopic eczema and contact dermatitis. The mechanisms of this exacerbation lie in the exacerbation of inflammation by concurrent types I and IV hypersensitivity reactions.

Treatment of laryngeal pathology associated with gastroesophageal reflux disease

To increase the effectiveness of the treatment of laryngeal pathology associated with gastroesophageal reflux disease (GERD), to determine the indications for the appointment of anti-inflammatory therapy to these patients. 120 patients were examined and treated, 58 of them men and 62 women, aged 30 to 82 years with GERD-associated laryngeal pathology. Three groups of patients were formed, comparable in age and gender, in accordance with the type of pachydermia in interarytenoid region; type 1 (40 patients) - pachydermia did not go beyond the middle of the interarytenoid cartilage (according to G.F. Ivanchenko), less than 3 mm, without signs of perifocal inflammation; type 2 (40 patients) - pachydermia of large size, extending beyond the middle of the interarytenoid cartilage with a spread to the entire interarytenoid region (according to G.F. Ivanchenko), often in combination with hyperkeratosis or epithelial dysplasia; type 3 (30 patients) - pachydermia of large size in combination with severe perifocal inflammation. All patients received antireflux therapy. Each group is divided into two subgroups: patients who did not receive anti-inflammatory therapy, and patients who received anti-inflammatory therapy, the basis of which was inhalation with degassed alkaline mineral water, as well as according to indications acetylcysteine, benzyldimethylammonium chloride 0.01% or hydroxymethylquinoxalindioxide, with severe swelling of the mucous membrane - budesonide. All patients completed the questionnaire "Reflux Symptoms Scale" before and after treatment. In group 2 patients (with type 2 pachydermia), the effectiveness of anti-inflammatory therapy was 75%. Of the 20 patients in this group, after inhaled therapy, 4 patients had pachydermia in interarytenoid region disappeared, 11 patients had type 1 pachydermia visualized, 5 (25%) patients had no pronounced dynamics. In group 3 patients (with type 3 pachydermia), the effectiveness of inhaled treatment was 100%, out of 15 patients after inhaled therapy, type 2 pachydermia was diagnosed in 8 patients, type 1 pachydermia - in 7 patients. In 4 patients, complex therapy led to the complete disappearance of reflux-associated laryngeal granulomas without surgical treatment. The effectiveness of inhaled therapy in relation to patient complaints after a month was 87%, while the effectiveness of treatment of patients without inhalation was 45%. Indications for the appointment of inhaled anti-inflammatory therapy in patients with reflux-associated pathology of the larynx are the presence of complaints of hoarseness, dryness, tickling, lump in the throat and chronic cough, endolaryngoscopic signs of exacerbation of chronic inflammation of the mucous membrane of the posterior larynx.

Anti-inflammatory therapy in patients with severe COVID-19 pneumonia: A single-center observational study

Anti-inflammatory therapy in patients with severe COVID-19 pneumonia: A single-center observational study

The role and place of bronchodilative and anti-inflammatory therapy for chronic obstructive pulmonary disease in patients with newly detected respiratory tuberculosis

Introduction. The relevance of the problem of managing patients with concomitant infectious and non-infectious pathology is beyond doubt, a third of patients suffering from tuberculosis have COPD as a comorbidity, which re-quires adequate therapy to improve the prognosis of the patient’s treatment as a whole. Objective: to evaluate the effectiveness of various options for bronchodilatory and anti-inflammatory therapy in patients with newly diag-nosed pulmonary tuberculosis secondary to COPD. Ma-terials and methods. A simple prospective comparative study included 210 patients divided into 3 groups: 124 pa-tients with TB+COPD; 46 patients with drug-susceptible TB (TB DS)+COPD; 40 patients with multidrug-resistant TB+COPD. The selection of treatment regimens was car-ried out with an assessment of the best efficiency, includ-ing inhaled glucocorticosteroid in combination with a long-acting β2-adrenergic agonist (IGCS/LABA) into the treatment regimens in the intensive phase of the course of TB. Duration of the follow-up is 6–9 months with assess-ment of X-ray pattern, bacterial shedding and smear neg-ativity as criteria for curing TB. Results. In patients with TB+COPD, the best effect of minimizing the severity of broncho-obstructive syndrome (reduction of dyspnea ac-cording to mMRC and CAT test) was obtained during ther-apy with a combination drug (long-acting anticholinergic drug and long-acting β2-agonist (LAAC/LABA) with good tolerance. In patients with TB DS+COPD, positive dynam-ics in the reduction of the severity of cough, dyspnea, CAT test was obtained in the ICS group in comparison with patients taking short-acting anticholinergic drugs (SDA). For patients with MDR+TB COPD, ICS/LABA showed the optimal effect on the severity of COPD symptoms. Against the background of taking IGCS/LABA in both groups, there was an increase in the number of patients achiev-ing smear negativity, cessation of bacterial shedding and closure of decay cavities, in comparison with the CAAC group, without any side effects. Conclusion. Adequate correction of broncho-obstructive syndrome in patients with COPD, including the use of bronchodilators (LABA) and anti-inflammatory drugs (IGCS) in the intensive phase of treatment of newly diagnosed pulmonary TB due to the main and additional effects of drugs, can improve the effectiveness of tuberculosis therapy

Excess comorbidities in gout: the causal paradigm and pleiotropic approaches to care.

Gout is a common hyperuricaemic metabolic condition that leads to painful inflammatory arthritis and a high comorbidity burden, especially cardiometabolic-renal (CMR) conditions, including hypertension, myocardial infarction, stroke, obesity, hyperlipidaemia, type 2 diabetes mellitus and chronic kidney disease. Substantial advances have been made in our understanding of the excess CMR burden in gout, ranging from pathogenesis underlying excess CMR comorbidities, inferring causal relationships from Mendelian randomization studies, and potentially discovering urate crystals in coronary arteries using advanced imaging, to clinical trials and observational studies. Despite many studies finding an independent association between blood urate levels and risk of incident CMR events, Mendelian randomization studies have largely found that serum urate is not causal for CMR end points or intermediate risk factors or outcomes (such as kidney function, adiposity, metabolic syndrome, glycaemic traits or blood lipid concentrations). Although limited, randomized controlled trials to date in adults without gout support this conclusion. If imaging studies suggesting that monosodium urate crystals are deposited in coronary plaques in patients with gout are confirmed, it is possible that these crystals might have a role in the inflammatory pathogenesis of increased cardiovascular risk in patients with gout; removing monosodium urate crystals or blocking the inflammatory pathway could reduce this excess risk. Accordingly, data for CMR outcomes with these urate-lowering or anti-inflammatory therapies in patients with gout are needed. In the meantime, highly pleiotropic CMR and urate-lowering benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors and key lifestyle measures could play an important role in comorbidity care, in conjunction with effective gout care based on target serum urate concentrations according to the latest guidelines.

Regulatory T-Cell Response to Low-Dose Interleukin-2 in Ischemic Heart Disease

BackgroundAtherosclerosis is a chronic inflammatory disease of the artery wall. Regulatory T cells (Tregs) limit inflammation and promote tissue healing. Low doses of interleukin (IL)-2 have the potential to increase Tregs, but its use is contraindicated for patients with ischemic heart disease.MethodsIn this randomized, double-blind, placebo-controlled, dose-escalation trial, we tested low-dose subcutaneous aldesleukin (recombinant IL-2), given once daily for 5 consecutive days. In study part A, the primary end point was safety, and patients with stable ischemic heart disease were randomly assigned to receive placebo or to one of five dose groups (range, 0.3 to 3.0 × 106 IU daily). In study part B, patients with acute non-ST elevation myocardial infarction or unstable angina were randomly assigned to receive placebo or to one of two dose groups (1.5 and 2.5 × 106 IU daily). The coprimary end points were safety and the dose required to increase circulating Tregs by 75%. Single-cell RNA-sequencing of circulating immune cells was used to provide a mechanistic assessment of the effects of aldesleukin.ResultsForty-four patients were randomly assigned to either study part A (n=26) or part B (n=18). In total, 3 patients withdrew before dosing, 27 received active treatment, and 14 received placebo. The majority of adverse events were mild. Two serious adverse events occurred, with one occurring after drug administration. In parts A and B, there was a dose-dependent increase in Tregs. In part B, the estimated dose to achieve a 75% increase in Tregs was 1.46 × 106 IU (95% confidence interval, 1.06 to 1.87). Single-cell RNA-sequencing demonstrated the engagement of distinct pathways and cell–cell interactions.ConclusionsIn this phase 1b/2a study, low-dose IL-2 expanded Tregs without adverse events of major concern. Larger trials are needed to confirm the safety and to further evaluate the efficacy of low-dose IL-2 as an anti-inflammatory therapy for patients with ischemic heart disease. (Funded by the Medical Research Council, the British Heart Foundation, and others; ClinicalTrials.gov number, NCT03113773)