Lippia origanoides and Thymus vulgaris Essential Oils Synergize with Ampicillin against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli.

(1) Background: Could compounds such as monoterpenes and sesquiterpenes present in essential plant oils inhibit bacterial growth as an alternative to help mitigate bacterial resistance? The purpose of this study is evaluating the in vitro antibacterial effect of Lippia organoides EO (LEO) and Thymus vulgaris EO (TEO), individually and in combination with ampicillin, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains; (2) Methods: Experimental in vitro design with post-test. The EOs were obtained by hydrodistillation and were analyzed by GC. ESBL-producing E. coli strains used were selected from urine cultures and the blaCTX-M and blaTEM resistance genes were identified by end point PCR. The disk diffusion method was used for the susceptibility tests. The MICs and MBCs were determined by microdilution test. Finally, the interaction effect was observed by checkerboard assay; (3) Results: A 39.9% decrease in the growth of the strain thymol in TEO and 70.4% in carvacrol in LEO was shown, observing inhibition halos of 32 mm for both EOs. MICs of 632 and 892 µg/mL for LEO and 738 and 940 µg/mL for TEO were determined. Finally, it was observed that, at low doses, there is a synergistic effect between TEO + LEO and EOs + ampicillin; (4) Conclusions: The findings demonstrate that TEO and LEO have an inhibitory effect on ESBL-producing E. coli, suggesting that they are candidates for further studies in the formulation of antibiotics to reduce bacterial resistance to traditional antibiotics.

Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis.

Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.

Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America.

Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data.

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

Management of cancer patients during COVID-19 pandemic at developing countries.

Cancer patient care requires a multi-disciplinary approach and multiple medical and ethical considerations. Clinical care during a pandemic health crisis requires prioritising the use of resources for patients with a greater chance of survival, especially in developing countries. The coronavirus disease 2019 crisis has generated new challenges given that cancer patients are normally not prioritised for admission in critical care units. Nevertheless, the development of new cancer drugs and novel adjuvant/neoadjuvant protocols has dramatically improved the prognosis of cancer patients, resulting in a more complex decision-making when prioritising intensive care in pandemic times. In this context, it is essential to establish an effective and transparent communication between the oncology team, critical care, and emergency units to make the best decisions, considering the principles of justice and charity. Concurrently, cancer treatment protocols must be adapted to prioritise according to oncologic response and prognosis. Communication technologies are powerful tools to optimise cancer care during pandemics, and we must adapt quickly to this new scenario of clinical care and teaching. In this new challenging pandemic scenario, multi-disciplinary work and effective communication between clinics, technology, science, and ethics is the key to optimising clinical care of cancer patients.

ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans.

BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.