Background
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that affects synovial joints. Cervical spine damage, due to rheumatoid inflammation, may produces atlantoaxial subluxation that can produce severe neurological symptoms. Early and aggressive treatment with disease-modifying anti-rheumatic drugs (DMARDs) has been shown to prevent cervical spine damage due to RA, but the effect of the biological therapy (BT) in this particular anatomical location, has not been well established.
Objectives
To analyze the prevalence of the anterior atlantoaxoidal subluxation (AAS) in RA patients receiving biological therapies and to assess possible risk factors.
Methods
X-Ray of 221 RA patients treated with at least one BT from December 1999 to December 2012 were analyzed. AAS was defined as an anterior atlantoaxoidal distance ≥3mm. All patients diagnosed of AAS prior to BT were excluded from this analysis and X-Ray from the remaining patients were reviewed at two Time points: before (T1) and after initiating the BT (T2). Epidemiological features (i.e. gender, age and age at diagnosis), clinical features (i.e. rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA) and erosions) and previous DMARDs were analyzed. Disease activity was established according to the index DAS28 at T2 radiographic control. The number of BT during the follow-up was also recorded.
A survival analysis of AAS was conducted according to two event models, namely (A) interval right-censored analysis [1], and (B) right-censored analysis with mid-point imputation where the time to AAS was approximately the half time between the BT starting date and the AAS positive X-Ray date. Univariate statistical analysis was performed using both the log rank test in models A and B and the Cox's proportional-hazards in model B. The latter was also used to perform the multivariate statistical analysis.
Results
58 (26%) patients were excluded from this analysis due to AAS prior BT. A total number of n=163 (74%) patients were analyzed. Of these, 89.5% were women, 73% had positive RF and 76% ACPA positive. Erosions were detected in 77% of patients. After BT initiation, AAS was observed in n=38 (23%) patients. The mean value of the period after starting BT and AAS diagnosis was 2.7 years. In the univariate analysis (i.e. Cox's test), it was found that RF positivity (P-value=8.56e-03), ACPA positivity (P-value=5.22e-03) and DAS28 (P-value=3.59e-03) were associated with AAS development.
In multivariate analysis only the presence of ACPA (P-value=8.57e-03) and elevated DAS28 (P-value=0.034) at the time of the X-Ray were associated with development of AAS. The duration of the disease was not significantly associated with the development of the AAS.
Conclusions
In our series of RA patients, it has been observed that AAS development was present in a substantial subset of patients in spite of having started biological therapy. The main risk factors for AAS development in these subgroup of patients was the presence of ACPA antibodies and hig...
In this work, screening of Lauraceae species for their antifungal activity against Collectotrichum tamarilloi was carried out and the ethanol extract derived from the bark of Endlicheria arenosa was found to be the best candidate. From the ethanolic extract of the bark of E. arenosa, the hexane and chloroform fractions were found to be active, from these five fatty acids were identified and two lactones were isolated. The most active fatty acid was the dodecanoic acid with a minimal inhibitory concentration (MIC) of 78.0 μM. The butyrolactone 3R,4R-licunolide A, it has not previously reported, and licunolide B show both the lowest MIC (55.3 μM). This is the first report of compounds of natural origin as growth inhibitors of C. tamarilloi.
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