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.

Objectives Anosmia/hyposomia have been described as early signs of COVID-19 infection in adults, including young asymptomatic patients who commonly refer olfactory disfunction as their only clinical manifestation. Very few studies involving paediatric age patients have been published until now. This study aims to determine the presence of olfactory dysfunction in children with COVID-19 infection through the use of a self-reported questionnaire and a new olfactory screening tool. Methods Nested case-control study. All paediatric patients screened by reverse transcription polymerase chain reaction (RT-PCR) and Anti-SARS-CoV-2 antibodies for COVID-19 infection, during the study period (March-May 2020), were asked to respond to a questionnaire about symptoms of olfactory disfunction. Patients above six years old also performed an odor identification test based on seven odorants (Kradeo®). This test was designed based on our cultural context and eating habits. Results 126 patients were recruited, including 33 with COVID-19 infection. 15% of the infected children referred anosmia and/or dysgeusia on the questionnaire, all of them were older than eleven years. The results of the odor test (69 patients) revealed subtle disturbances in the infected group (mostly misrecognition of odorants). Median odorant recognition was 3 odors [Interquartile range (IQR) 2-4] in case group and 4 [IQR 3-5] in controls. Male patients showed significantly larger disturbances than girls in both groups (p=0.03). Conclusion Self-referred prevalence of olfactory disfunction in our sample of infected children is lower than that described in adults, especially among the youngest ones, maybe due to immature development of angiotensin-converting enzyme 2 (ACE2) receptors expressed in nasal mucosa. Nevertheless, one month after infection, subtle disturbances (misrecognition of odors) were identified among the infected children. This screening olfactory test provides a hygienic, user-friendly tool, suitable for screening children older than six years of age.

Within our cohort, PARIS and PRECISE-DAPT were fairly to moderately effective for the prediction of bleeding. Their predictiveness varies according to the bleeding severity. PARIS-derived bleeding risk assessment was associated with a higher net benefit compared to PRECISE-DAPT-based bleeding risk assessment.

What is known and objective: Initial treatment recommendations of COVID-19 were based on the use of antimicrobial drugs and immunomodulators. Although information on drug interactions was available for other pathologies, there was little evidence in the treatment of COVID-19. The objective of this study was to analyse the potential drug-drug interactions (pDDIs) derived from the medication used in COVID-19 patients in the first pandemic wave and to evaluate the real consequences of such interactions in clinical practice.Methods: Cohort, retrospective and single-centre study carried out in a third-level hospital. Adult patients, admitted with suspected COVID-19, that received at least one dose of hydroxychloroquine, lopinavir/ritonavir, interferon beta 1-b or tocilizumab and with any pDDIs according to "Liverpool Drug Interaction Group" between March and May 2020 were included. The possible consequences of pDDIs at the QTc interval level or any other adverse event according to the patient's medical record were analysed. A descriptive analysis was carried out to assess possible factors that may affect the QTc interval prolongation.Results and discussion: Two hundred and eighteen (62.3%) patients of a total of 350 patients admitted with COVID-19 had at least one pDDI. There were 598 pDDIs.Thirty-eight pDDIs (6.3%) were categorized as not recommended or contraindicated. The mean value difference between baseline and pDDI posterior ECG was 412.3 ms ± 25.8 ms vs. 426.3 ms ± 26.7 ms; p < 0.001. Seven patients (5.7%) had a clinically significant alteration of QTc. A total of 44 non-cardiological events (7.3%) with a possible connection to a pDDI were detected.

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DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis.

Background. Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer. Methods. A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Results. A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82−8.67), oral cancer (OR = 2.58; 1.67−3.99) and oropharyngeal cancer (OR = 17.71; 6.42−48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65−27.82), oral cancer (OR = 2.95; 1.23−7.08) and oropharyngeal cancer (OR = 38.50; 22.43−66.07). Conclusions. Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator.