The Gut Microbiota and Inflammation in Rheumatoid Arthritis

“Mutualism” is a well-defined relationship that describes a form of cooperation between two living organisms of different species that ends up with a beneficial outcome for each one. Any disruption to such a relationship by an external trigger or a potential intruder puts at risk the well-being of both. In humans, oral and gut microbiota provide a noteworthy model of beneficial mutualism. Multiple recent evidences point to the possible pathologic consequences of a disruption to this ecosystem (altered microbiota profile or dysbiosis) on human well-being. The gut-joint axis found its clear way “Proof of Principle” in the pathogenesis of autoimmune rheumatic diseases including rheumatoid arthritis (RA), seronegative spondyloarthropathies, and Behcet’s disease in a number of studies. Current therapeutic trends are directed towards the diverse biologic and immune-pathogenic factors involved in the disease process. Addressing dysbiosis in RA features an attractive future therapeutic target. In this chapter, authors aim to explore the recent evidences regarding the pathogenic role of “gut dysbiosis” in rheumatoid arthritis (RA), highlighting the spectrum of immune-pathogenic events that might contribute to disease evolution and inspecting future directives of research

Genomic characterization of SARS-CoV-2 in Egypt: insights into spike protein thermodynamic stability

The overall pattern of the SARS-CoV-2 pandemic so far has been a series of waves; surges in new cases followed by declines. The appearance of novel mutations and variants underlie the rises in infections, making surveillance of SARS-CoV-2 mutations and prediction of variant evolution of utmost importance. In this study, we sequenced 320 SARS-CoV-2 viral genomes isolated from patients from the outpatient COVID-19 clinic in the Children’s Cancer Hospital Egypt 57357 (CCHE 57357) and the Egypt Center for Research and Regenerative Medicine (ECRRM). The samples were collected between March and December 2021, covering the third and fourth waves of the pandemic. The third wave was found to be dominated by Nextclade 20D in our samples, with a small number of alpha variants. The delta variant was found to dominate the fourth wave samples, with the appearance of omicron variants late in 2021. Phylogenetic analysis reveals that the omicron variants are closest genetically to early pandemic variants. Mutation analysis shows SNPs, stop codon mutation gain, and deletion/insertion mutations, with distinct patterns of mutations governed by Nextclade or WHO variant. Finally, we observed a large number of highly correlated mutations, and some negatively correlated mutations, and identified a general inclination toward mutations that lead to enhanced thermodynamic stability of the spike protein. Overall, this study contributes genetic and phylogenetic data, as well as provides insights into SARS-CoV-2 viral evolution that may eventually help in the prediction of evolving mutations for better vaccine development and drug targets

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The effectiveness of the anti-tumor necrosis factor therapy infliximab in neuro-Behçet’s disease: a systematic review and meta-analysis

Objective To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet’s disease. Methods In this systematic review and meta-analysis, the research question was designed using the ‘Population, Intervention, Comparator, and Outcomes’ (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I 2 statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence. Results Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I 2  = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years. Conclusion Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet’s disease

Patterns of pulmonary involvement in an Egyptian cohort with autoimmune diseases: a descriptive study

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Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters

Aim The aim of the study was to assess serum levels of interleukin (IL)-18 and IL-10 in systemic lupus erythematosus (SLE) patients and their relationship with disease activity. Patients and methods Thirty patients with SLE and 20 healthy controls were investigated in this study. The serum IL-18 and IL-10 levels were determined using enzyme-linked immunosorbent assay and their correlations with the disease activity were measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and laboratory parameters, including erythrocyte sedimentation rate, anti-ds DNA antibody, complement 3, and complement 4 levels were analyzed. Results The serum IL-18 and serum IL-10 levels were significantly higher (mean values 1770.2 ± 360.4 and 842.65 ± 315.37 pg/ml for IL-18 and IL-10, respectively) in SLE patients compared with the controls (110.65 ± 30.37 vs. 76 ± 14.2 pg/ml, respectively, P < 0.001). The increase in serum levels of IL-18 and IL-10 directly and significantly correlated with each other (r = 0.404, P = 0.037). Furthermore, such an increase in the levels of these two cytokines showed a highly significant positive correlation with the SLEDAI scores and anti-ds DNA in the studied patients (P < 0.001). Conclusion The circulating IL-18 and IL-10 concentrations were significantly elevated in SLE patients and correlated with the SLEDAI score. The study emphasized that there exists an upregulated proinflammatory as well as anti-inflammatory responses in patients with active SLE; however, the anti-inflammatory response is not enough to suppress the active disease. Identifying the exact contribution of the currently studied cytokines might provide future insights for targeted therapeutic strategies in SLE

Psoriasis paradox—infliximab-induced psoriasis in a patient with Crohn’s disease: a case report and mini-review

Biologic drugs are therapeutic modalities designed to inhibit specific cytokine signaling pathways. The introduction of these drugs in the management of autoimmune diseases has dramatically changed the treatment paradigm of chronic systemic immune-mediated inflammatory disorders. However, despite their overall acceptable safety profiles, paradoxical reactions have been reported in some real-life cases including case studies and clinical trials. In this study, we report a patient with Crohn’s disease who developed infliximab-induced psoriasis vulgaris after starting infliximab treatment. In this case, infliximab was discontinued, and low-dose steroids and subcutaneous methotrexate were introduced to control both his psoriasis and bowel condition with satisfying responses

Relapse rates after elective discontinuation of anti-TNF therapy in rheumatoid arthritis: a meta-analysis and review of literature

Abstract Background Inhibitors of tumor necrosis factor alpha (TNF-α) are current mainstay of therapies for rheumatoid arthritis (RA). The decision when to withdraw TNF-α inhibitors after achieving remission and the incidence of relapse rates with elective discontinuation are both important questions that demand intense survey in these patients. In this meta-analysis we aimed to estimate the magnitude of relapse rate after elective TNF-α inhibitor discontinuation in RA patients with remission. Methods Systematic searches of PubMed/MEDLINE, Cochrane Library databases, grey literature (unpublished and ongoing trials) from the WHO International Clinical Trials Registry Platform and the US National Institutes of Health were performed for studies reporting the outcomes of elective discontinuation of TNF-α inhibitor in RA patients after remission. Random-effects models for meta-analyses were conducted on extracted data. Results Out of 390 references screened, 16 RCTs were included. Meta-analysis of 1264 patient data revealed a relapse rate of 0.47 (95% CI 0.41–0.54). Sensitivity analysis showed that none of the studies had higher influence on the results. Conclusions Almost half of all the RA patients in remission relapse after elective TNF-α inhibitor discontinuation. This information might be useful when considering this management option with individual patients