ObjectiveThe aim of this study was to assess whether the CYP2C9*2 and/or *3 variants might modify the risk for NSAID-related upper gastrointestinal bleeding (UGIB) in NSAID users.Patients and methodsWe conducted a multicenter, case–control study in which cases were patients aged more than 18 years with a diagnosis of UGIB, and controls were matched (1 : 3) by sex, age, date of admission, and hospital. Exposure was defined as the mean number of defined daily doses (DDDs) of NSAIDs metabolized by CYP2C9 in the week preceding the index date. Three DDD categories were defined (0, ≤0.5, and >0.5). Exposure was constructed taking both NSAID use and CYP2C9 polymorphisms into account. Patients of non-European origin were excluded from the analysis.ResultsA total of 577 cases and 1343 controls were finally included in the analysis: 103 cases and 89 controls consumed NSAIDs metabolized by CYP2C9, and 88 cases and 177 controls were CYP2C9*3 carriers. The adjusted odds ratios (aORs) of UGIB associated with the CYP2C9*2 and wild-type alleles proved to be similar [OR=8.79 (4.50–17.17) and 10.15 (2.92–35.35), respectively] and lower than those of the CYP2C9*3 allele [aOR=18.07 (6.34–51.53)] for consumers taking more than 0.5 DDDs of NSAIDs metabolized by CYP2C9. Grouping genotypes into carriers and noncarriers of the CYP2C9*3 variant resulted in aORs of 16.92 (4.96–57.59) for carriers and 9.72 (4.55–20.76) for noncarriers, where DDDs were greater than 0.5.ConclusionThe presence of the CYP2C9*3 variant increases the risk for UGIB associated with NSAID for DDDs greater than 0.5. The presence of the CYP2C9*2 allele shows no such effect.

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Background: Saliva represents a promising non-invasive source of novel biomarkers for diagnosis and prognosis cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the value of saliva as an alternative liquid biopsy. Materials and methods: We performed a systematic review and meta-analysis. PubMed, Embase, LILACS and the Cochrane Library were searched to identify articles that examined the potential of salivary biomarkers for the diagnosis of malignant non-oral tumours. To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR), area under hierarchical summary receiver operating characteristic (AUC) curve, sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) using a random-or fixed-effects model. Heterogeneity and publication bias were assessed. Statistical tests were two-sided. Results: One hundred fifty-five study units from 29 articles with 11,153 subjects were included.

Silicosis is a diffuse interstitial lung disease caused by sustained inhalation of silica and silicates. Several cytokines are activated by their inhalation and can mediate the process of pulmonary fibrosis. The identification of biomarkers could allow an early diagnosis before the development of radiological alterations and help monitor the evolution of patients. The objetive of this study was to determine the clinical significance of specific biomarkers, to estimate their association with the development, severity and/or progression of silicosis, and identify determinants of this evolution. We conducted a prospective observational study in patients attending the pulmonology clinic from 2009 to 2018. Serum levels of the following inflammatory mediators were assessed: interleukin-6 (IL-6), interleukin 2 receptor subunit alpha (IL2R) interleukin 1 beta (IL1B), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-β1), alpha-1 antitrypsin (AAT), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin in subjects exposed to silica, with and without silicosis. Association between those inflammatory mediators with lung function measurements and radiological severity of disease and their impact on prognosis were analysed. 337 exposed to silica (278 with silicosis) and 30 subjects in the control group were included. IL-8, α1AT, ferritin, CRP and LDH levels were higher in silicosis than in those exposed to silica without silicosis. IL-8, LDH and AAT levels were associated with progression of silicosis and IL-6, IL-8, LDH, AAT, ferritin, and CRP with vital status. The results of the ROC analysis indicated the potential of IL-8 as a biomarker in the presence of silicosis and for the prediction of mortality.