Measuring disease activity and response to treatment in rheumatoid arthritis

Introduction: Effective treatment of rheumatoid arthritis (RA) requires suppression of the underlying inflammation. Measurement of such inflammation, the disease activity, is mandatory to target treatment and maximize outcomes. However, this is not as straightforward as it may seem.

Areas covered: The many tools developed to measure disease activity in RA, from composite scores and patient-reported outcomes, to laboratory markers and imaging are discussed, with a focus on their utility in guiding therapy and assessing response. The complex issues in measuring disease activity in RA, whether in clinical trials or normal clinical practice, and in the context of national guidelines and recommendations, available time, and resources are considered.

Expert commentary: The key to effective management of RA is the rapid suppression of inflammation, ideally to remission, with maintenance of such remission. The aim is to prevent disability and maximize quality of life. Central to this is the ability to determine disease activity (potentially open to suppression) as opposed to damage (irreversible). A variety of measures are currently available, allowing better assessment of response to treatment. In the future, the development of predictive biomarkers allowing targeting of drugs may revolutionize this field and render the tools of today redundant.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Diet and nutrition against inflammatory bowel disease: Trick or treat(ment)?

Even if the relationships between nutrition and inflammatory bowel disease (IBD) remain underexplored, the current literature is providing, day by day, much more evidence on the effects of various diets in both prevention and treatment of such illnesses. Wrong dietary habits, together with other environmental factors such as pollution, breastfeeding, smoke, and/or antibiotics, are among the theoretical pathogenetic causes of IBD, whose multifactorial aetiology has been already confirmed. While some of these risk factors are potentially reversible, some others cannot be avoided, and efficient treatments become necessary to prevent IBD spread or recurrence. Furthermore, the drugs currently available for treatment of such disease provide low-to-no effect against the symptoms, making the illnesses still strongly disabling. Whether nutrition and specific diets will prove to effectively interrupt the course of IBD has still to be clarified and, in this sense, further research concerning the applications of such dietary interventions is still needed.     

Angiographic profile and outcomes in persistent non-valvular atrial fibrillation: A study from tertiary care center in North India

BackgroundThe relationship of atrial fibrillation (AF) with coronary artery disease (CAD) is well established, yet it is often missed. There is evidence of myocardial ischemia on stress imaging in AF patients in the absence of obstructive CAD. In this prospective cohort, we studied the angiographic profiles of non-valvular AF patients.MethodsThe study was a nonrandomized, prospective, single-center observational study of consecutive patients of persistent non-valvular AF. Patients symptomatic for AF despite optimal medical therapy for 3 months were recruited and all underwent coronary angiograms (CAG). Patients with prior history of CAD were excluded.ResultsA total of 70 patients were followed for a mean duration of 12 ± 1.4 months. The mean age of the study group was 66.07 (±11.49) years. Hypertension was the commonest comorbidity seen in 74% patients. Obstructive CAD was present in 32 (46%) patients, non-obstructive (<50% stenosis) CAD in 17 (24%) patients and normal coronaries in 21 (30%) patients. Overall 49 (70%) patients had evidence of CAD. Amongst patients without obstructive CAD, slow flow was seen in 16 (42%) patients. Lower baseline ejection fraction, lower haemoglobin & albumin levels and higher creatinine levels was associated with increased mortality. In patients without obstructive CAD, hospitalizations for fast ventricular rate were significantly increased in those having slow flow on CAG (p = 0.005).ConclusionsMajority (70%) of our patients had evidence of atherosclerotic CAD on CAG. A large proportion of patients without obstructive CAD had slow flow on CAG.     

Cardiac-type total anomalous pulmonary venous return is not benign

ObjectiveThe objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC).MethodsThis single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined.ResultsThe connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001).ConclusionsThe number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making.     

Egg Intake Has No Adverse Association With Blood Lipids Or Glucose In Adolescent Girls

Objective: Longitudinal data on cardiometabolic effects of egg intake during adolescence are lacking. The current analyses aim to evaluate the impact of usual adolescent egg consumption on lipid levels, fasting glucose, and insulin resistance during late adolescence (age 17–20?years).

Methods: Data from 1392 girls, aged 9 to 10 at baseline and followed for 10?years, in the National Heart, Lung, and Blood Institute’s National Growth and Health Study were used to examine the association between usual egg intake alone and in combination with other healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and insulin resistance, measured as homeostasis model assessment of insulin resistance (HOMA-IR). Diet was assessed using 3-day food records during eight examination cycles. Girls were classified according to usual weekly egg intake, ages 9–17?years:?<1 egg/wk (n?=?361), 1 to <3 eggs/wk (n?=?703), and ≥3 eggs/wk (n?=?328). Analysis of covariance modeling was used to control for confounding by other behavioral and biological risk factors.

Results: Girls with low, moderate, and high egg intakes had adjusted low-density lipoprotein cholesterol levels of 99.7, 98.8, and 95.5 mg/dL, respectively (p?=?0.0778). In combination with higher intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were stronger and statistically significant. There was no evidence that ≥3 eggs/wk had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who consumed ≥3 eggs/wk had the lowest levels of insulin resistance.

Conclusion: These results suggest that eggs may be included as part of a healthy adolescent diet without adverse effects on glucose, lipid levels, or insulin resistance.