Introduction: Osteoarthritis is a growingly common joint disorder affecting older adults. It is characterized by chronic low-grade inflammation, a phenomenon by itself considered a cardiovascular risk factor. However, data on its potential impact on cardiovascular disease (CVD) is scarce. Assessing hand osteoarthritis (HOA) might be advantageous when studying CVD as this particular location might be less affected by traditional cardiovascular risk factors such as overweight and physical activity. Hypothesis: HOA is associated with subclinical CVD. Methods: We cross-sectionally assessed the relationship between HOA and CVD in 1,803 women from the Mexican Teachers’ Cohort, excluding those with history of myocardial infarction, cerebrovascular disease, and rheumatoid arthritis. From 2012 to 2016, a subsample of the MTC participants from Mexico City and the states of Nuevo LeÓn, Chiapas, and YucatÅn were invited for clinical examinations in which standardized neurologists measured their carotid intima-media thickness (IMT) with ultrasound and a standardized HOA questionnaire was applied. HOA was defined as having ≥45 years, hand joint pain, and morning stiffness that lasts no longer than 30 minutes. Subclinical CVD was assessed through log-transformed IMT, and carotid atherosclerosis (CAS) was defined as mean right or left carotid IMT ≥0.8 mm or the presence of atherosclerotic plaque. Multivariable linear and logistic regression analyses were used to evaluate the association between HOA and IMT and CAS adjusting for age, state, smoking, alcohol consumption, diabetes, hypertension and body mass index. Results: Among participants with a mean age of 51 years (±4), 18.4% met the criteria for HOA, and the prevalence of CAS was 23.1%. After multivariable adjustment, women diagnosed with HOA had 1.6% (95%CI 0.2, 3.1) higher mean IMT than those without the joint disease. Similarly, women with HOA had 35% (95%CI 1.01, 1.81) higher odds of CAS. Sensitivity analyses using a less stringent definition of OA (pain regardless of stiffness), as well as incapacitating pain, did not have a significant association with CAS. Conclusion: Among middle-aged women, HOA was associated with subclinical CVD. This relation might be due to low-grade chronic inflammation, but further research is needed to clarify the underlying mechanisms, the role of screening for HAO as part of cardiovascular risk profiling, and the value of potential interventions such as anti-inflammatory drugs.
e21511 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tumor biopsy represents the standard for molecular diagnosis, nevertheless it is not always feasible to obtain. Liquid Biopsy (LB) may offer an alternative in the first line setting. Methods: Retrospective review of case files and next generation sequencing report (NGS) from LB from patients in a Validation Trial, performed from January 2018 to September 2019. We present the molecular alterations and clinical characteristics of the population. Results: 147 records and LB reports of patients 18 years and older with metastatic lung adenocarcinoma without prior treatment were included. 40% of the population had been selected based on a commercial local PCR test for EGFR (Idylla). 49% of them were female with Mean age of 60.9 ± 12.7. 56% had a history of smoking with an average packs/year of 20.5 (1-156) and 39% had exposure to wood smoke, 92% had an ECOG 0-1. 65 % of the Patients were diagnosed in Clinical Stage (8th Edition) IVA and 22% in IVB. 13% had SNC metastasis. The LB detected genomic alterations in 85.5% of the cases. 78% represent pathogenic mutations and 7.5% variants of uncertain significance (VUS).14.5% of the biopsies could not detect any ctDNA. The most frequent aberrations reported were TP53 in 51.7%, KRAS 16%, EGFR 16%, ALK 9%, PIK3CA 4%, RET 4%, BRAF 3%, BRCA 3, and HER2 3%. In addition, 20% had bTMB ≥10. Only 20% of the patients could receive a targeted therapy or immunotherapy of the potential ≈50%. Most cases had co-mutations (1-6 x case). Looking for factors associated with the presence of bTMB by a logistic regression model, it was possible to identify the presence of CNS metastases and smoking as identified with an OR of 3,688 (p = 0. 0.042) and 3.952 (p = 0. 024) respectively. Conclusions: It is feasible to have tumor molecular analysis through liquid biopsy in most cases, with genetic alterations previously reported in tumor tissue in the first line setting. [Table: see text]
e21544 Background: A relationship between EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been consistently demonstrated. Nonetheless, consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation. Methods: The present study is a prospective single-blind analysis of skin biopsies of patients with confirmed advanced EGFR mutated lung adenocarcinoma. Immunohistochemistry was performed with EGFR, p27, Ki67, STAT3, and MAPK, as well as an H&E histopathological analysis, looking for their relationship with the response to treatment with tyrosine kinase inhibitors. ROC curve analysis was used to determine the cutoff value for each biomarker selected dichotomizing the response to treatment as mentioned in the tissue samples section (adequate response or no response). Kaplan Meier analysis for progression-free survival was performed. Results: From the 35 biopsies obtained, 21 (60%) of the patients were women and 14 (40%) men; the mean age of participants was 60.6±11.7 years. Twelve patients (34.3%) were at the pre-treatment group, 12 (34.3%) had an adequate response to treatment and 11 (31.4%) were at the no response to treatment group. The median progression-free survival was 9 months. The next biomarkers were significantly related to an adequate response to treatment by using a bivariate correlation test: EGFR (p = 0.025), Ki67 (p = 0.015), STAT3 (p = 0.017), stratum corneum thickness (p = 0.039) and the number of layers of the stratum corneum(p = 0.041). A better median of progression-free survival was obtained on those with a value above of the cutoff preestablished of EGFR (21 months versus 7 months, 95% CI 0-46 versus 4.23-9.77, p = 0.025) and number of layers of the stratum corneum (21 months versus 8 months, 95% CI 0-43.81 versus 6.72-9.28, p = 0.030), however, for p27 a better median of progression-free survival was shown in those with a value below the cutoff before mentioned (21 months versus 8 months, 95% CI 8.17-33.83 versus 6.87-9.13, p = 0.031). Conclusions: We found a relationship between EGFR, Ki67, STAT3, stratum corneum, number of layers of stratum corneum, with the response to treatment, and better progression-free survival for high expression EGFR, number of layers of the stratum corneum and low expression for p27. The present study should incite to perform a further investigation to validate these markers as potential prognostic and predictive factors.
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