RESUMO
BACKGROUND: Epigenetic biomarkers in cancer have emerged as promising tools for early detection, prognosis, and treatment response prediction. In cervical cells, hypermethylation of the host and viral HPV-genome increases with the severity of lesions, providing a useful biomarker in the triage of hr-HPV-positive women and during treatment. The present study focuses on evaluating the clinical performance of the FAM19A4/miR124-2 methylation test in a population-based cervical screening program. METHODS: Previously collected cervical samples, after bisulfite-converted DNA, were analyzed by PreCursor-M+ kit (distributed by Fujirebio Europe), for DNA methylation. The sensitivity, specificity, and negative/positive predictive values of DNA methylation were compared to histology, colposcopy, the HPV-DNA test, and cytology results. RESULTS: Among the 61-sample set, the specificity of methylation vs. positive histology (≥CIN2) and colposcopy (≥G2) were 87% and 90%, whereas the sensitivity was 50% and 33.3%, respectively. The combination of methylation analysis with standard methods increases diagnostic accuracy. CONCLUSIONS: Overall, we found a good specificity of DNA methylation in comparison to currently used techniques. Further larger studies could support the use of FAM19A4/miR124-2 as reliable biomarkers in the prevention of cervical cancer as triage in the screening protocol.
RESUMO
Background: Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is endemic globally, causing severe infections in hospitalized patients. Surveillance programs help monitor and promptly identify the emergence of new clones. We reported the rapid spread of a novel clone of K. pneumoniae co-harbouring class A and D carbapenemases in colonized patients, and the potential risk factors involved in the development of infections. Methods: Rectal swabs were used for microbiological analyses and detection of the most common carbapenemase encoding genes by real-time PCR (i.e., blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP). All strains co-harbouring KPC and OXA-48 genes were evaluated. For each patient, the following variables were collected: age, sex, length and ward of stay, device use, and outcome. Clonality of CR-Kp was assessed by preliminary pulsed field gel electrophoresis (PFGE), followed by multi-locus sequence typing (MLST) analyses. Results: A total of 127 isolates of K. pneumoniae co-harbouring KPC and OXA-48 were collected between September 2019 and December 2020. The median age (IQR) of patients was 70 (61-77). More than 40% of patients were admitted to intensive care unit (ICU). Around 25% of patients developed an invasive infection, the majority of which were respiratory tract infections (17/31; 54.8%). ICU stay and invasive infection increased the risk of mortality (OR: 5.39, 95% CI: 2.42-12.00; OR 6.12, 95% CI: 2.55-14.69, respectively; p-value ≤ 0.001). The antibiotic susceptibility test showed a resistance profile for almost all antibiotics considered. Monoclonal origin was confirmed by PFGE and MLST showing a similar restriction pattern and belonging to ST-512. Conclusions: We report the spread and the marked antibiotic resistance profiles of K. pneumoniae strains co-producing KPC and OXA-48. Further study could clarify the roles of clinical and microbiological variables in the development of invasive infection and increasing risk of mortality, in colonized patients.
