Background

Circulating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia.

Methods

A retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization.

Results

A total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels.

Conclusion

Lower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.

OBJECTIVE: To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. METHODS: Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. RESULTS: A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. CONCLUSION: We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.

Antibodies to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) have been reported in pooled healthy donor plasma and intravenous immunoglobulin products (IVIG). It is not known whether administration of IVIG increases circulating anti-SARS-CoV-2 antibodies (COVID ab) in IVIG recipients. COVID ab against the receptor binding domain of the spike protein were analyzed using a chemiluminescent microparticle immunoassay in patients with idiopathic inflammatory myopathies (IIM) both receiving and not receiving IVIG (IVIG and non-IVIG group, respectively). No significant differences in COVID ab levels were noted between IVIG and non-IVIG groups (417 [67-1342] AU/mL in IVIG vs 5086 [43-40,442] AU/mL in non-IVIG, p = 0.11). In linear regression models including all post-vaccination patient samples, higher number of vaccine doses was strongly associated with higher COVID ab levels (2.85 [1.21, 4.48] log AU/mL, regression coefficient [Formula: see text] [95% CI], p = 0.001), while use of RTX was associated with lower ab levels (2.73 [- 4.53, - 0.93] log AU/mL, [Formula: see text][95%CI], p = 0.004). In the IVIG group, higher total monthly doses of IVIG were associated with slightly higher COVID ab levels (0.02 [0.002-0.05] log AU/mL, p = 0.04). While patients on IVIG did not have higher COVID ab levels compared to the non-IVIG group, higher monthly doses of IVIG were associated with higher circulating levels of COVID ab in patients receiving IVIG, particularly in patients concomitantly receiving RTX. Our findings suggest that IIM patients, especially those at increased risk of COVID infection and worse COVID outcomes due to RTX therapy may have protective benefits when on concurrent IVIG treatment.

Objectives

Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients.

Methods

A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes.

Results

The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes.

Conclusions

The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

Objective

SSc is clinically and aetiopathogenically heterogeneous. Consensus standards for more uniform trial design and selection of outcome measures are needed. The objective of this study was to develop evidence-based points to consider (PTCs) for future clinical trials in SSc.

Methods

Thirteen international SSc experts experienced in SSc clinical trial design were invited to participate. One researcher with experience in systematic literature review and three trainees were also included. A systematic review using PubMed and the Cochrane Central Register of Controlled Trials was conducted and PTCs when designing clinical trials in SSc were developed. As part of that development we conducted an Internet-based Delphi exercise regarding the main points to be made in the consensus statement. Consensus was defined as achieving a median score of ≥7 of 9.

Results

By consensus, the experts decided to develop PTCs for each individual organ system. The current document provides a unifying outline on PTCs regarding general trial design, inclusion/exclusion criteria and analysis. Consensus was achieved regarding all the main points of the PTCs.

Conclusion

Using European League Against Rheumatism suggestions for PTCs, a general outline for PTCs for controlled clinical trials in SSc was developed. Specific outlines for individual organ systems are to be published separately. This general outline should lead to more uniform and higher-quality trials and clearly delineate areas where further research is needed.

OBJECTIVE: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. METHODS: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. RESULTS: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. CONCLUSION: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.