Outcomes of undifferentiated peripheral inflammatory arthritis in real-world practice. A longitudinal cohort study.

OBJECTIVES: Undifferentiated peripheral inflammatory arthritis (UPIA) may have 3 different courses, including evolution to differentiated arthritis, remaining undifferentiated, and self-limited course. The purpose of this study was to provide a real-world evidence for predictors of outcomes in UPIA in a longitudinal cohort of patients. METHODS: Patients enrolled in the CTDRC-UA cohort were screened for eligibility. Inclusion criteria were: (i) having synovitis in ≥ 1 joint, (ii) not meeting the criteria of any other rheumatic disease, (iii) having at least 2 visits per year, iv) included in the cohort during the period of 2004 to 2021, and (v) having active disease at cohort entry. Two hundred and three patients who met the inclusion criteria were followed up until January 2023. RESULTS: Medication-free remissions occurred in 42 (20.7%) cases. In 24 (11.8%) cases, the disease met the criteria of other rheumatic diseases, of which rheumatoid arthritis (RA) was the most common. In addition, joint damage occurred in 33 (16.3%) cases. Predictors of medication-free remissions were absence of comorbidity, starting a sustained remission at ≤ 6 months, and having no flare. Factors associated with disease evolution to RA were anti-citrullinated peptide antibody (ACPA) positivity, non-adherence to therapy, not going into sustained remission and having flare. Delay in treatment for > 3 months and being ACPA positive were the predictors of joint damage. CONCLUSION: Although the majority of UIPA cases treated with step-up combination therapy with DMARDs do not progress to RA, most require continued treatment and a few achieve medication-free remissions. Key Points • Undifferentiated peripheral inflammatory arthritis (UPIA) can progress to rheumatoid arthritis in 11% of cases; and lack of sustained remission, being anti-citrullinated peptide antibody positive, non-adherence to therapy, and having flare are its predictors. • Medication-free remissions occur in 21% of patients with UPIA; and absence of comorbidity, starting a sustained remission at ≤ 6 months, and having no flare are its predictors. • Initiating treatment in the window of opportunity may lead to a better joint outcome.

Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.

OBJECTIVES: Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of RASSF1 and ATIC genes their potential implication in the pathogenesis of lung tumor in Iranian patients. METHODS: In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both RASSF1 and ATIC genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene's methylation. RESULTS: Methylation of RASSF1 gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of ATIC gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both RASSF1 and ATIC genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer. CONCLUSIONS: Methylation levels of both RASSF1 and ATIC genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.

Systemic Inflammatory Index Is a Novel Predictor of Intubation Requirement and Mortality after SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19), with an increasing number of deaths worldwide, has created a tragic global health and economic emergency. The disease, caused by severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-19), is a multi-system inflammatory disease with many of COVID-19-positive patients requiring intensive medical care due to multi-organ failures. Biomarkers to reliably predict the patient's clinical cause of the virus infection, ideally, to be applied in point of care testing or through routine diagnostic approaches, are highly needed. We aimed to probe if routinely assessed clinical lab values can predict the severity of the COVID-19 course. Therefore, we have retrospectively analyzed on admission laboratory findings in 224 consecutive patients from four hospitals and show that systemic immune inflammation index (SII) is a potent marker for predicting the requirement for invasive ventilator support and for worse clinical outcome of the infected patient. Patients' survival and severity of SARS-CoV-2 infection could reliably be predicted at admission by calculating the systemic inflammatory index of individual blood values. We advocate this approach to be a feasible and easy-to-implement assay that may be particularly useful to improve patient management during high influx crisis. We believe with this work to contribute to improving infrastructure availability and case management associated with COVID-19 pandemic hurdles.

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.

BACKGROUND: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. METHODS: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. FINDINGS: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. INTERPRETATION: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. FUNDING: None.