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Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla™ Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-naïve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-naïve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla™ Biocartis platform is feasible and reliable in mCRC patients in clinical practice.

ABSTRACT Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy. Methods This multicenter prospective study evaluates the changes in ABP after 12 weeks of dapagliflozin 10 mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25 mL/min/1.73 m2. Primary endpoint was the change of nighttime systolic blood pressure (SBP). Changes of daytime SBP, prevalence of normal dipping (day/night SBP ratio <0.9) and changes in ABP patterns, that is, sustained uncontrolled hypertension (SUCH), white coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and controlled hypertension (CH) were secondary endpoints. Results Eighty-three of 96 patients completed the study [age 68.7 ± 8.9 years, 73.5% males, GFR 49 ± 17 mL/min/1.73 m2, median albuminuria: 0.18 (interquartile range 0.10–0.38) g/24 h]. After 12 weeks of dapagliflozin, nighttime SBP declined by −3.0 mmHg (95% confidence interval −5.2/−0.8 mmHg; P = .010) with an improvement of nighttime SBP goal (<110 mmHg) from 18.0% to 27.0% (P < .001). Similarly, the prevalence of normal dipping increased (from 31.3% to 50.6%, P = .005). A decrease in daytime (−2.4 mmHg; P = .046) and office (−7.9 mmHg; P = .009) SBP was also found. The decline of ambulatory and office SBP was associated with increased prevalence of CH (from 6.0% to 18.0%) and significant improvement of SUCH, WUCH and MUCH (P = .009). Albuminuria decreased (P < .001), whereas eGFR did not change (P = .297). Urinary tract infection (4.2%) and acute kidney injury (3.6%) were the main causes of drop-out. Only one patient showed a drop of nighttime SBP below 90 mmHg. Conclusions Dapagliflozin is associated with improvement in circadian blood pressure rhythm with no major safety signal related to excessive blood pressure decrease.

The Authors present a paper with a dual goal: in vitro evaluation of the elution of vancomycin and monitoring of its bactericidal action when the antibiotic is used in acrylic cement. Discs of cement with different concentrations of vancomycin alone or combined with meropenem were prepared. To assess the elution of vancomycin the discs were kept in physiological solution and periodically sampled for five weeks. The bactericidal action was assessed by putting the antibiotic discs in contact with colonies of Staphylococcus, Enterococcus, Pseudomonas and Escherichia coli . Two combinations of antibiotic-loaded cement were tested: the first one to act as a spacer and the second to stabilise the revision prosthesis.