Influence of KRAS mutations on clinical outcome in patients with curatively resected stage III colon cancer treated with adjuvant chemotherapy.

OBJECTIVE: To profile and correlate KRAS mutations with outcome in stage III colon cancer (CC) patients who underwent adjuvant chemotherapy following curative resection surgery. PATIENTS AND METHODS: In this retrospective study, eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with fluoropyrimidine monotherapy (FP) or with oxaliplatin-based regimens (O-FP). Disease-free survival (DFS) and overall survival (OS) were analyzed and computed using the Kaplan-Meier method and the log-rank test. RESULTS: The study population included 148 patients (n=65 FP and n=83 O-FP). We identified KRAS mutations in 41/148 (27%) patients, of which 18 (44%) received FP and 23 (56%) O-FP. Five-year DFS and OS were significantly higher in patients with KRAS wild-type vs. mutant [DFS: 78 vs. 56%, HR: 0.47 (95% CI: 0.25; 0.87), p=0.01; OS: 73 vs. 68%, HR: 0.44 (95% CI: 0.21; 0.88), p=0.01]. In patients treated with FP, the 5-year DFS and OS was significantly improved in the KRAS wild-type vs. mutant group, respectively [DFS: 80 vs. 43%, HR: 2.88 (95% CI: 0.67; 3.76), p=0.014; OS: 85 vs. 68%, HR: 0.27 (95% CI: 0.10; 0.73), p=0.005]. Conversely, 5-year DFS and OS were not statistically different for patients with KRAS wild-type vs. mutations treated with O-FP, respectively [DFS: 78 vs. 65%, HR: 1.59 (95% CI: 0.67; 3.76), p=0.281; OS: 80 vs. 75%, HR: 0.73 (95% CI: 0.55; 2.12), p=0.57)]. CONCLUSIONS: Our results suggest that curatively resected stage III CC patients exhibiting wild-type KRAS status might benefit from FP alone. Conversely, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.

CT protocol optimisation in PET/CT: a systematic review.

PURPOSE: Currently, no consistent guidelines for CT scans used within PET/CT examinations are available. This systematic review provides an up-to-date overview of studies to answer the following questions: What are the specific CT protocols used in PET/CT? What are the possible purposes of requiring a CT study within a PET/CT scan? Is the CT protocol obtained from a dosimetric optimisation study? MATERIALS AND METHOD: PubMed/MEDLINE, Cochrane Library, Embase and Scopus were systematically searched for relevant studies in accordance with the PRISMA statement. The literature search was conducted from January 2007 until June 2019. Data derived from studies were standardized in order to reduce possible biases, and they were divided into clinically homogeneous subgroups (adult, child or phantom). Subsequently, we divided the CT protocol intents into 3 types (anatomic localization only, attenuation correction only and diagnostic purpose). A narrative approach was used to summarise datasets and to investigate their heterogeneity (due to medical prescription methodology) and their combination in multiseries CT protocols. When weighted computed tomography dose index (CTDIw) was available, we calculated the volumetric computed tomography dose index (CTDIvol) using the pitch value to make the results uniform. Eventually, the correlation between protocol intents and CTDIvol values was obtained using a Kruskal-Wallis one-way ANOVA statistical test. RESULT: Starting from a total of 1440 retrieved records, twenty-four studies were eligible for inclusion in addition to two large multicentric works that we used to compare the results. We analyzed 87 CT protocols. There was a considerable range of variation in the acquisition parameters: tube current-time product revealed to have the most variable range, which was 10-300 mAs for adults and 10-80 mAs for paediatric patients. Seventy percent of datasets presented scans acquired with tube current modulation, 9% used fixed tube current and in 21% of them, this information was not available. Dependence between mean CTDIvol values and protocol intent was statistically significant (p = 0.002). As expected, in diagnostic protocols, there was a statistically significant difference between CTDIvol values of with and without contrast acquisitions (11.68 mGy vs 7.99 mGy, p = 0.009). In 13 out of 87 studies, the optimisation aim was not reported; in 2 papers, a clinical protocol was used; and in 11 works, a dose optimisation protocol was applied. CONCLUSIONS: According to this review, the dose optimisation in PET/CT exams depends heavily on the correct implementation of the CT protocol. In addition to this, considering the latest technology advances (i.e. iterative algorithms development), we suggest a periodic quality control audit to stay updated on new clinical utility modalities and to achieve a shared standardisation of clinical protocols. In conclusion, this study pointed out the necessity to better identify the specific CT protocol use within PET/CT scans, taking into account the continuous development of new technologies.

Spatio-temporal variability of airborne bacterial communities and their correlation with particulate matter chemical composition across two urban areas.

The study of spatio-temporal variability of airborne bacterial communities has recently gained importance due to the evidence that airborne bacteria are involved in atmospheric processes and can affect human health. In this work, we described the structure of airborne microbial communities in two urban areas (Milan and Venice, Northern Italy) through the sequencing, by the Illumina platform, of libraries containing the V5-V6 hypervariable regions of the 16S rRNA gene and estimated the abundance of airborne bacteria with quantitative PCR (qPCR). Airborne microbial communities were dominated by few taxa, particularly Burkholderiales and Actinomycetales, more abundant in colder seasons, and Chloroplasts, more abundant in warmer seasons. By partitioning the variation in bacterial community structure, we could assess that environmental and meteorological conditions, including variability between cities and seasons, were the major determinants of the observed variation in bacterial community structure, while chemical composition of atmospheric particulate matter (PM) had a minor contribution. Particularly, Ba, SO4 (2-) and Mg(2+) concentrations were significantly correlated with microbial community structure, but it was not possible to assess whether they simply co-varied with seasonal shifts of bacterial inputs to the atmosphere, or their variation favoured specific taxa. Both local sources of bacteria and atmospheric dispersal were involved in the assembling of airborne microbial communities, as suggested, to the one side by the large abundance of bacteria typical of lagoon environments (Rhodobacterales) observed in spring air samples from Venice and to the other by the significant effect of wind speed in shaping airborne bacterial communities at all sites.

Antibiotic resistance in bacteria associated with coarse atmospheric particulate matter in an urban area.

AIMS: To assess antibiotic resistance in airborne bacteria associated with coarse particulate matter (PM10) in an urban area, with specific considerations about the Staphylococcus genus. METHODS AND RESULTS: Disc diffusion test was performed on 243 microbial strains, isolated from PM10 in winter and summer and belonging to families Pseudomonadaceae and Enterobacteriaceae and genera Acinetobacter, Enterococcus and Staphylococcus. Staphylococci resistances were the most heterogeneous, being distributed among almost all tested antibiotics. Staphylococcus isolates resistant to some selected antibiotics were further investigated for the presence of the corresponding genetic determinants. Only tetK, which mediates the tetracycline resistance through the action of an efflux protein, was found in almost all resistant isolates. CONCLUSIONS: The lack of specific genetic determinants makes their transmission among staphylococci less likely. This may reduce the theoretical risk associated with the inhalation of airborne micro-organisms. SIGNIFICANCE AND IMPACT OF STUDY: Although the spreading of antibiotic resistant micro-organisms is of particular concern in clinical settings, the origin of antibiotic resistance genes can be traced in natural environments. As behaviour, viability and transport of bacteria in the atmospheric compartment suffer from a lack of information, the evaluation of the actual risk posed by airborne micro-organisms to human health is still challenging.