Aim: The main objective of this study was to determine the prevalence of real DDIs between immunosuppressants and other drugs in transplant patients. Methods: We conducted a prospective, observational 1-year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi-Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The data were analyzed using Statistical Package for Social Sciences (SPSS) package v. 25.0 (IBM Corp., Armonk, NY, USA). Results: A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18–79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with anti-fungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n=5), followed by hypertension (1.3%; n=4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non-steroidal anti-inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. Conclusion: There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

Associations between colorectal cancer (CRC) survival and mutations in mediator of MAPK/ERK (RAS-BRAF-MEK-ERK) and PIK3CA/AKT signaling pathways have been reported. The objective of this study was to evaluate the influence of mutations in the EGFR pathway (KRAS, NRAS, BRAF and PIK3CA) on overall survival in CRC. We conducted a retrospective observational cohort study comprising 194 paraffin tumor samples from patients diagnosed with colorectal cancer were analyzed for KRAS codons 12, 13 and 61, NRAS codons 12, 13 and 61, BRAF and PIK3CA exons 9 and 20 gene mutations. Multivariate analysis confirmed that patients with ECOG of 0 presented lower risk of death (HR = 0.17, CI95%, 0.10 -0.31, p = 1656.10-9) compared to a higher ECOG (Table 4). The only independent genetic association was between PIK3CA20 mutation (H1047Y; rs121913281) and higher risk of death (HR = 8.93, CI95%, 1.20-66.57, p = 0.03268). No association was found between the rest of the mutations analyzed and overall survival. To explore the effect of mutations in patients with different degrees of ECOG, a stratified analysis was performed. Multivariate analysis in patients with ECOG 0 group confirmed the association between mutations of PIK3CA and an increased risk of death: E545K (HR = 5.49, CI95%, 1.28-23.51, p = 0.021720) and H1047Y (HR = 53.49; %, 4.63-617.40, p = 0.001429). In conclusion, our results show PIK3CA gene mutations may predict the overall survival of CRC patients, positioning PIK3CA as a potential biomarker for survival in CRC.