Autoimmunity to citrullinated type II collagen in rheumatoid arthritis

The production of autoantibodies to citrullinated type II collagen and the citrullination of type II collagen were analyzed in rheumatoid arthritis. Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum samples from 130 rheumatoid arthritis patients. Autoantibodies to native noncitrullinated type II collagen were detected in 14.6% of serum samples, all of which were positive for anti-citrullinated type II collagen antibodies. Serum samples were also positive for anti-citrullinated type II collagen antibodies in 1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis patients, and 18 psoriatic arthritis patients were all negative for anti-citrullinated type II collagen antibodies. Anti-citrullinated type II collagen antibodies and fragments of citrullinated type II collagen were found in the synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis patients. Moreover, anti-citrullinated type II collagen antibodies were isolated from the synovium of affected knee joints in 8 rheumatoid arthritis patients using antigen/antibody immunocomplex dissociation buffer but not by using standard buffers. These findings indicate that autoantibodies that react with citrullinated type II collagen are specifically produced and that immunocomplexes composed of fragments of citrullinated type II collagen and autoantibodies are deposited in the inflamed articular synovium in rheumatoid arthritis patients. Assaying for the presence of anti-citrullinated type II collagen antibodies may therefore be useful for diagnosing rheumatoid arthritis, and the deposition of these immunocomplexes in the articular synovium may be involved in pathogenesis

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Agreement Between Guideline Thresholds Using an “All‐in‐One” Device to Measure Office, Home, and Ambulatory Blood Pressures

Background Blood pressure (BP) thresholds for diagnosing and managing hypertension vary for office, home, and ambulatory readings, and between guideline documents. This analysis determined corresponding office, home, and ambulatory BP thresholds using baseline data from the HI‐JAMP (Home‐Activity Information and Communication Technology–Based Japan Ambulatory Blood Pressure Monitoring Prospective) study, which used a validated “all‐in‐one” BP monitoring device. Methods and Results Data from 2322 treated patients with hypertension who underwent office BP measurement, then 24‐hour ambulatory BP monitoring, then home BP monitoring for 5 days were analyzed. Corresponding BP thresholds for office, home, and ambulatory measurements were determined using Deming regression. Values equivalent to office systolic BP (SBP) of 120 and 140 mm Hg were as follows: 115.9 and 127.7 mm Hg for 24‐hour ambulatory SBP; 120.8 and 134.0 mm Hg for daytime ambulatory SBP; 104.9 and 117.9 mm Hg for nighttime ambulatory SBP; and 122.0 and 134.2 mm Hg for morning‐evening average home SBP. Deming regression showed that morning‐evening average home SBP and daytime ambulatory SBP were almost the same (home SBP=0.99×daytime ambulatory SBP+0.27 mm Hg; r=0.627). Morning‐evening average home SBP values of 120 and 135 mm Hg were equivalent to daytime ambulatory SBP values of 119.1 and 133.9 mm Hg, respectively. A home SBP threshold of 130 mm Hg corresponded to 24‐hour and nighttime ambulatory SBP values of 123.5 and 113.6 mm Hg, whereas a home SBP threshold of 135 mm Hg corresponded to 24‐hour and nighttime ambulatory SBP values of 128.0 and 119.2 mm Hg. Conclusions Ambulatory and home BP thresholds in this analysis were similar to those proposed by existing guidelines. The similarity between the home BP and daytime ambulatory BP thresholds was a clinically relevant finding

Effect of Brassinolide Applied at the Meiosis and Flowering Stages on the Levels of Endogenous Plant Hormones during Grain-Filling in Rice Plant (Oryza salivaL.)

Brassinolide (BL), a brassinosteroid, applied to rice plants in pots promotes panicle ripening. In this study, we examined the effect of BL applied at the meiosis and flowering stages on endogenous levels of various plant hormones in the panicles of the rice plant (cv. Nipponbare) grown in a field-temperature (F-temp; 25°G on average ranging from 22 to 33°C during ripening periods) condition and low-temperature (L-temp; in phytotron kept at 22°C/ 17°C) condition in rice cultivation season in Japan. The content of either free- or bound-IAA in the rice spikelet at the milk-ripe stage (10 - 15 days after heading) was higher in the F-temp condition than in the L-temp condition. BL applied twice, 10 days before and on the day of heading, slightly increased the free-IAA content and greatly increased the bound-IAA content at the milk-ripe stage in both condition. BL slightly decreased the ABA content of the spikelet at the milk-ripe stage in the F-temp condition, and slightly increased it in the L-temp condition. The rate of ethylene production was measured only in the F-temp condition. It was markedly high at the milk-ripe stage and low at the dough-ripe stage (21 days after heading). BL treatment clearly increased the rate of ethylene production from the panicles under both light and dark conditions at the milk-ripe stage. These results suggest that BL, which promotes rice ripening, influences in the levels of endogenous plant hormones to play an important role in controlling the sink function during grain-filling