Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients.

OBJECTIVES: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome. METHODS: A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. RESULTS: In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response. CONCLUSION: DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD.

C-reactive protein, D-dimer, erythrocyte sedimentation rate, and troponin in intensive care unit patients with COVID-19 in Iran.

Background: The coronavirus disease 2019 (COVID-19) pandemic in Iran has led to a lack of intensive care unit (ICU) facilities. This study examines C-reactive protein (CRP), D-dimer, erythrocyte sedimentation rate (ESR), and troponin in ICU patients with COVID-19 in comparison to COVID-19 patients admitted to the wards in Iran. Materials and Methods: In a case-control study, troponin, CRP, ESR, and D-dimer were compared in the case samples of 109 COVID-19 patients admitted to the ICU, and in the control group, 140 COVID-19 patients admitted to the wards. Results: The mean of CRP (P < 0.001) and D-dimer (P < 0.001) was higher, whereas troponin (P < 0.001) was lower in patients admitted to the ICU, but no significant difference was observed between the values of ESR (P = 0.292) in the two groups. Conclusion: This study showed that the values of CRP and D-dimer were higher in patients admitted to the ICU, but no significant difference was observed between the values of ESR in the two groups.

The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain.

BACKGROUND CONTEXT: Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups. PURPOSE: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain. STUDY DESIGN: Cross-sectional study in UK Biobank (UKB) and TwinsUK. PATIENT SAMPLES: A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments. OUTCOME MEASURES: Ever having had LBP associated with disability lasting ≥1 month (LBP1). METHODS: Using the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms. RESULTS: In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4 -2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR = 2.5 [95% CI 1.7-3.7], p=2.6×10-6), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=0.002), with small-magnitude and/or non-significant associations in the lowest two PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤0.05). CONCLUSIONS: Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.

Evaluation of the Association between Antiphospholipid Antibodies and ICU Admission Outcome in Critically Ill COVID-19 Patients in Iranian Population.

Background: The role of anti-phospholipid antibodies (aPLs) in the prognosis of COVID-19 patients is controversial. In order to prove the role of this factor, the necessary measures such as early initiation of anticoagulants should be started even in the early stages of the disease and in outpatients or the use of other drugs in addition to anticoagulants. We decided to investigate the role of these antibodies in ICU admission outcomes in critically ill COVID-19 patients. Methods: The case-control study was carried out in Isfahan, Iran, from March to September 2021. One hundred nine patients in the case group were selected, including patients admitted to the ICU with a COVID-19 diagnosis. The 140 patients in the control group were selected from hospitalized and outpatients with COVID-19 with PCR + and pulmonary involvement, similar to the case group without the need for ICU hospitalization. The anti B2GP1 (IgM, IgG) and anti-cardiolipin (IgM, IgG)) were compared in two groups. Results: The frequency percentage of patients in the abnormal group of anti-phospholipid antibodies was about 10% in total. No statistically significant difference in these aPLs in continued measures was observed between the two groups of patients admitted to the ICU and those outside the ICU. Also, in the logistics regression analysis, no significant association was observed. Conclusions: Therefore, the cause of coagulation in patients admitted to the ICU is not related to these aPLs. This means that aPLs could not be a good predictor of patient admission to the ICU.

Fear and anxiety in patients with multiple sclerosis during COVID-19 pandemic; report of an Iranian population.

BACKGROUND: There are reports that stress-related disorders are increasing during coronavirus disease 2019 (COVID-19) pandemic. Patients with Multiple Sclerosis (MS) are at higher risk of developing psychiatric disorders, which result in worsening of their disability. There are concerns about the mental health of MS patients during this pandemic. OBJECTIVE: We aimed to evaluate the prevalence of anxiety, depression, and levels of fear about Corona in MS patients during the COVID-19 pandemic. MATERIALS AND METHODS: This was a cross-sectional study on MS patients who were admitted to the MS clinics affiliated with Isfahan University of medical sciences from May to June 2020. Anxiety and depression were evaluated according to the Hospital Anxiety and Depression Scale (HADS). The Corona Fear Questionnaire developed by Ahorsu et al. was applied to evaluate the state of fear about COVID-19. Chi-square tests were used to compare depression and anxiety between different groups, Kruskal-Wallis was used for fear scores, Spearman correlation coefficient was also reported for correlations. RESULTS: 410 MS patients with a mean age of 38.6 years (±10.35) were enrolled in the study. Among those patients who answered the HADS questionnaire completely (n=399, n=388, for anxiety and depression subscales respectively) the prevalence of anxiety and depression were 31.2% (n=128) and 39.3% (n=161), respectively. There was no significant relationship between anxiety and depression with any of the following variables: sex, marital status, history of drug abuse, smoking, duration of taking psychiatric medication, being tested for COVID-19, being quarantined. Regarding fear about COVID-19, patients with depression or anxiety showed higher scores on the fear questionnaire (p-value=0.03, p-value=0.008 respectively). CONCLUSIONS: The prevalence of anxiety and depression in MS patients was higher than previously reported. Fear about COVID-19 was correlated with anxiety and depression. Multicenter studies are required to develop specific recommendations for screening mental health problems in MS patients during COVID pandemic.