Background
Osteogenic circulating endothelial progenitor cells (EPC) play a pathogenic role in cardiovascular system degeneration through promulgating vasculature calcification, but its role in ...conduction disorders as part of the cardiovascular degenerative continuum remained unknown.
Aim
To investigate the role of osteocalcin (OCN)‐expressing circulating EPCs in cardiac conduction disorders in the unique clinical sample of rheumatoid arthritis (RA) susceptible to both abnormal bone metabolism and cardiac conduction disorders.
Methods
We performed flow cytometry studies in 134 consecutive asymptomatic patients with rheumatoid arthritis to derive osteogenic circulating OCN‐positive (OCN+) CD34+KDR+ vs. CD34+CD133+KDR+ conventional EPC. Study endpoint was the prespecified combined endpoint of electrocardiographic conduction abnormalities.
Results
Total prevalence of cardiac conduction abnormality was 9% (n = 12). All patients except one had normal sinus rhythm. One patient had atrial fibrillation. No patient had advanced atrioventricular (AV) block. Prevalence of first‐degree heart block (>200 ms), widened QRS duration (>120 ms) and right bundle branch block were 6.7%, 2.1%, and 2.2% respectively. Circulating osteogenic OCN+CD34+KDR+ EPCs were significantly higher among patients with cardiac conduction abnormalities (p = 0.039). Elevated OCN+CD34+KDR+ EPCs> 75th percentile was associated with higher prevalence of cardiac conduction abnormalities (58.3% vs. 20.02%, p = 0.003). Adjusted for potential confounders, elevated OCN+CD34+KDR+ EPCs> 75th percentile remained independently associated with increased risk of cardiac conduction abnormalities (OR = 4.4 95%CI 1.2–16.4, p = 0.028). No significant relation was found between conventional EPCs CD34+CD133+KDR+ and conduction abnormalities (p = 0.36).
Conclusions
Elevated osteogenic OCN+CD34+KDR+ EPCs are independently associated with the presence of electrocardiographic conduction abnormalities in patients with rheumatoid arthritis, unveiling a potential novel pathophysiological mechanism.
Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in ...hospitalized COVID-19 patients.
We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0).
Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio HR, 6.59; 95% confidence interval CI, 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4.
Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.
NCT04647695.
Concerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac ...vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals.
This is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users (≥16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution.
This study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10–1.94).
Autoimmune conditions requiring hospital care are rare following mRNA and inactivated COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events.
•Severe autoimmune conditions following mRNA and inactivated virus COVID-19 vaccines are rare.•Population-based active surveillance is imperative for vaccine safety monitoring.•Long-term autoimmune safety of COVID-19 vaccine warrants further investigation.
Aim
Carers may offer valuable insight into the true health status of patients with rheumatoid arthritis (RA). This multinational, multi‐stakeholder, exploratory study in Australia, China and Japan ...aimed to enrich our understanding of the role and potential impact of carers on RA management.
Method
This study used a 2‐phase sequential mixed methods approach involving 3 key stakeholder groups: rheumatologists, RA patients and carers. The first phase involved an in‐depth qualitative exploratory survey (n = 30), which informed the development of the subsequent quantitative validation survey (n = 908). In both phases, patients and carers provided self‐assessments of disease and support parameters.
Results
In the qualitative phase, patients usually understated the amount of physical support required, compared to carers. Rheumatologists underestimated the amount of physical and emotional care required, compared to carers and patients; however, in the quantitative phase, rheumatologists overestimated the level of support provided by carers. Levels of support provided by carers increased as disease severity increased. Active participation of carers in clinical consultations and treatment decision‐making was deemed important by 55% of all patients and 82% of all carers. All stakeholders believed carers’ insights into the physical and emotional conditions of patients were useful and should be considered in clinical decision‐making. Over 95% of rheumatologists reported soliciting input from the carer.
Conclusion
Carers provide valuable input that can give clinicians greater insight into the patients’ physical and emotional states, and treatment adherence. Development of standardized carer‐reported outcomes that correlate with patient‐reported outcomes and clinical parameters will ensure clinical meaningfulness and external validity.
Beta-lactams (BL) are the most frequently reported drug allergy, but the vast majority of patients are found not to be genuinely allergic after evaluation. Few studies have investigated the clinical ...predictors of genuine BL allergy, and the prevalence in hospitalized Chinese patients is unknown.
Patients admitted to a tertiary hospital in Hong Kong (HK) were analyzed to identify the prevalence and factors associated with the presence of BL allergy labels among hospitalized Chinese patients. A combined cohort of patients having completed allergy investigation for suspected BL allergies in the United Kingdom (UK) and HK were analyzed to identify predictors of genuine allergy.
The prevalence of BL allergy labels in hospitalized HK Chinese was 5%, which was associated with female gender and concomitant non-BL antibiotic allergy labels. The rate of genuine BL allergy patients referred for suspected allergies in the UK and HK cohort was only 14%. History of anaphylaxis and interval of less than a year since the index reaction were independent clinical predictors of genuine BL allergy. The negative predictive value of penicillin skin testing was 90%, confirming the need for drug provocation testing after negative skin testing. There was a high rate of confirmed piperacillin-tazobactam allergy.
The estimated true prevalence of genuine BL allergy in hospitalized HK Chinese is around 0.5%. This high rate of BL mislabeling highlights the need for comprehensive allergy evaluation and screening. History of anaphylaxis and duration since the index reaction are important predictors of genuine allergy. Piperacillin-tazobactam allergy may pose a unique challenge in this population with a high prevalence of suspected allergies, surging antibiotic resistance, and lack of testing available.
Spondyloarthritis (SpA) has a significant impact on patients' quality of life due to functional impairments. Generic health instruments like the EuroQoL 5-dimension (EQ-5D) is important for the ...cost-utility analysis of health care interventions and calculation of quality-adjusted life years. However, the applicability of the EQ-5D health measure in Chinese patients with SpA is currently unknown. Hence, the aim of the study is to test the psychometric properties and to validate the use of the EQ-5D health measure for utility analyses in Chinese patients with SpA.
Prospective and consecutive recruitment of 220 Chinese patients with SpA was conducted. Demographic data including smoking and drinking habits, education level, income, and occupation was collected. Disease-associated data including disease duration, the presence of back pain, peripheral arthritis, dactylitis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease was also recorded. Questionnaires regarding disease activity and functional disability (BASDAI, BASFI, BASGI, BASMI, ASDAS, ODI), mental health (HADS depression and anxiety), and the EQ-5D scores were recorded. SF-36 scores were used to verify the findings. Baseline correlations were performed along with test-retest reliability, validity, and internal consistency tests. Specifically, the relationship between EQ-5D and disease activity and functional scores was studied.
EQ-5D scores achieved acceptable internal consistency and reliability. A ceiling effect was observed for all domains of the EQ-5D except for pain/discomfort. No floor effect was observed. Significant negative correlations were observed between ODI, HADS, BASFI, BASMI, BASDAI, and ASDAS-CRP and with EQ-5D. A higher disease activity was well-differentiated by EQ-5D, as with the disability and mental health scores.
The EQ-5D demonstrates satisfactory psychometric properties for assessment of SpA patients. It has high utility for demonstrating changes in disease activity and disability.
Lupus in the far east: a modern epidemic Li, Philip H.; Lau, Chak‐Sing
International journal of rheumatic diseases,
20/May , Letnik:
20, Številka:
5
Journal Article
Recenzirano
Systemic lupus erythematosus (SLE) is a diverse and heterogeneous disease with much variation between different ethnicities. Although more severe and prevalent in non‐Caucasian populations, the bulk ...of evidence regarding ‘Asian lupus’ had traditionally been extrapolated from studies on patient minorities in the West. Lupus research in Asia has since grown exponentially and now takes a leading role in improving the care for SLE patients worldwide. With recent advances, particularly from studies in population‐specific phenotyping, genome‐wide association studies, lupus nephritis and innovative treatment modalities, we now have an expanding understanding of both the basic science and clinical management of SLE. Upcoming breakthroughs from growing multi‐ethnic cohorts and international collaborations will likely bring further important ramifications for SLE management in the near future.
Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ...ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.
•SLE is a B cell-dominated systemic immune disorder, whereas IDLE is a B cell-dominated skin-localized autoimmune dermatosis.•IDLE and SLE are different diseases with distinct pathogenesis.•IDLE is a tissue-restricted disease, in which tissue-specific autoantibodies originate from skin-localized ectopic GCs.
Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease that predominantly affects young females. Dysregulation of different immune cell populations leads to self-tolerance ...breakdown and subsequent multiple organ damage as the disease develops. Plasmacytoid dendritic cells (pDCs) are potent producers of type I interferon (IFN), while myeloid dendritic cells (mDCs) are more specialized in antigen presentations. We have previously reported that bone-marrow (BM)-derived pDCs from the murine lupus model New Zealand black/white F1 (BWF1) possess abnormalities. Therefore, this study continues to investigate what aberrant properties peripheral pDCs and mDCs possess in BWF1 and how they mediate SLE progression, by comparing their properties in pre-symptomatic and symptomatic mice. Results showed that CD11chiCD11b+ myeloid DCs expanded during the disease state with down-regulation of co-stimulatory molecules and major histocompatibility complex class II molecules (MHC II), but their capacity to stimulate T cells was not hampered. During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. Moreover, the expressions of myeloid differentiation primary response 88 (Myd88) and nuclear factor kappa B subunit 1 (Nfkb1) were higher in CD11chiCD11b+ DCs at the disease stage, leading to higher nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation activity. In summary, we reported aberrant phenotypic properties with enhanced TLR7/9 responses of CD11chiCD11b+ DCs in SLE mediated by aberrant NF-κB signaling pathway. Our findings add additional and novel information to our current understanding of the role of DCs in lupus immunopathogenesis. Lastly, molecular candidates in the NF-κB pathway should be exploited for developing therapeutic targets for SLE.
To compare the utility of Diffusion weighted imaging (DWI) with short tau inversion recovery (STIR) sequence in the diagnosis of early axial spondyloarthritis (SpA).
Three hundred and five patients ...with chronic back pain were recruited consecutively from 3 rheumatology centers. Clinical, radiological and blood parameters were recorded. Patients with back pain duration no more than 3 years were classified as having early disease. STIR sequence and DWI of the sacroiliac joints were obtained and assessed using the Spondyloarthritis Research Consortium of Canada (SPARCC) method. The Assessment in Spondyloarthritis international Society definition was used to define positive STIR and DWI. Results were compared to expert diagnosed axial SpA.
When compared to STIR sequence, DWI had similar sensitivity (STIR 0.29, DWI 0.30) and specificity (STIR 0.97, DWI 0.92) in diagnosing sacroiliitis. However, STIR sequence had better reliability (STIR 0.78, DWI 0.61). In early disease group, DWI was not better than STIR sequence in detecting active sacroiliitis (sensitivity DWI vs STIR: 0.34 vs 0.36; specificity DWI vs STIR: 0.93 vs 0.93; positive predictive value DWI vs STIR: 0.92 vs 0.92; negative predictive value DWI vs STIR: 0.36 vs 0.37). Using the Assessment in SpondyloArthritis international Society (ASAS) classification criteria, 67/98 patients with early disease (sensitivity 0.91 specificity 0.90) and 221/305 overall (sensitivity 0.90; specificity 0.92) were classified as axial SpA. Among the expert diagnosed axial SpA patients who did not meet the ASAS criteria, only 2 had positive DWI.
DWI and STIR have similar sensitivity in diagnosing axSpA in early disease. However, the use of DWI is limited by poorer reliability when compared with STIR.
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