(36,13). A melhor diferença verificou-se para a sub-escala Autoritarismo (5º ano -1º ano = 2,03), e a pior diferença verificou-se para a sub-escala Benevolência (5º ano -1º ano = 0,39). Os melhores resultados foram encontrados no final do 3º ano. Discussão: Os resultados poderão dever-se ao módulo de luta contra o estigma, incluído na disciplina de 'Introdução à Saúde Mental'. Esse efeito positivo ter-se-á perdido no 4º e 5º anos, com uma degradação das atitudes. Conclusão: Este estudo salienta a importância dos módulos de luta contra o estigma na melhoria das atitudes dos estudantes de medicina perante a saúde mental. Este tipo de acções pedagógicas preventivas com intuito anti-estigma, devem ser na melhor preparação possível de gerações médicas futuras. Palavras-chave: Atitude; Estigma Social; Estudantes de Medicina; Psiquiatria. ABSTRACT Introduction:This study aims to assess the impact of psychiatric education on attitudes of medical students towards psychiatric patients. Material and Methods:A cross-sectional survey of medical students was conducted at the biggest Portuguese medical school. The students completed an anonymous self-report questionnaire, including sociodemographic data, family history of psychiatric illness, and the Community Attitudes toward the Mentally Ill scale. Results: Of the 2 178 students, 398 answered the survey, representing 18.2% of the whole medical school. There was a significant improvement in all Community Attitudes toward the Mentally Ill scale dimensions along the medical course. The higher scores were in Restrictiveness subscale (38.01), and the lower scores were for Authoritarianism (36.13). The best improvement along the course was for Authoritarianism (5 th year score -1 st year score = 2.03), and the worse was for Benevolence (5 th year score -1 st year score = 0.39). The biggest improvement, in all scores, was found at the end of the 3rd year. Discussion: The authors propose that the better attitudes found on third year students were due to a very specific anti-stigma module on the theoretical discipline 'Introduction to Mental Health'. After that, this positive effect was lost, with fourth and fifth year medical students showing a worsening of their attitudes. Conclusion: Our results highlight the importance of anti-stigma specific education modules in order to improve students' attitudes toward mental health. Thus more anti-stigma preventive measures can be taken onward, on preparing the best way possible, the next generation of doctors.

Introduction Inflammation is a critical component in carcinogenesis. The neutrophil-to-lymphocyte ratio (nlr) has been retrospectively studied as a biomarker of prognosis in metastatic colorectal cancer (mcrc). Compared with a low nlr, a high nlr is associated with worse prognosis. In the present study, we compared real-world survival for patients with mcrc based on their nlr group, and we assessed the utility of the nlr in determining first-line chemo­therapy and metastasectomy benefit. Methods In this retrospective and descriptive analysis of patients with mcrc undergoing first-line chemotherapy in a single centre, the last systemic absolute neutrophil and lymphocyte count before treatment was used for the nlr. A receiver operating characteristic curve was used to estimate the nlr cut-off value, dividing the patients into low and high nlr groups. Median overall survival (mos) was compared using Kaplan–Meier curves and the log-rank test. A multivariate analysis was performed using a Cox regression model. Results The 102 analyzed patients had a median follow-up of 15 months. Regardless of systemic therapy, approx­imately 20% of patients underwent metastasectomy. The nlr cut-off was established at 2.35, placing 45 patients in the low-risk group (nlr < 2.35) and 57 in the high-risk group (nlr ≥ 2.35). The Kaplan–Meier analysis showed a mos of 39.1 months in the low-risk group and 14.4 months in the high-risk group (p < 0.001). Multivariate Cox regression on the nlr estimated a hazard ratio of 3.08 (p = 0.01). Survival analysis in each risk subgroup, considering the history of metastasectomy, was also performed. In the low-risk group, mos was longer for patients undergoing metastasectomy than for those not undergoing the procedure (95.2 months vs. 22.6 months, p = 0.05). In the high-risk group, mos was not statistically different for patients undergoing or not undergoing metastasectomy (24.3 months vs. 12.7 months, p = 0.08). Conclusions Our real-world data analysis of nlr in patients with mcrc confirmed that this biomarker is useful in predicting survival. It also suggests that nlr is an effective tool to choose first-line treatment and to predict the benefit of metastasectomy.

BACKGROUND Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) improves prognosis in locally advanced gastric cancer (LAGC). Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are prognostic biomarkers but not predictive factors. AIM To assess blood ratios’ (NLR, LMR and PLR) potential predictive response to FLOT and survival outcomes in resectable LAGC patients. METHODS This was a multicentric retrospective study investigating the clinical potential of NLR, LMR, and PLR in resectable LAGC patients, treated with at least one preoperative FLOT cycle, from 12 Portuguese hospitals. Means were compared through non-parametric Mann-Whitney tests. Receiver operating characteristic curve analysis defined the cut-off values as: High PLR > 141 for progression and > 144 for mortality; high LMR > 3.56 for T stage regression (TSR). Poisson and Cox regression models the calculated relative risks/hazard ratios, using NLR, pathologic complete response, TSR, and tumor regression grade (TRG) as independent variables, and overall survival (OS) as the dependent variable. RESULTS This study included 295 patients (mean age, 63.7 years; 59.7% males). NLR was correlated with survival time ( r = 0.143, P = 0.014). PLR was associated with systemic progression during FLOT ( P = 0.022) and mortality ( P = 0.013), with high PLR patients having a 2.2-times higher risk of progression [95% confidence interval (CI): 0.89-5.26] and 1.5-times higher risk of mortality (95%CI: 0.92-2.55). LMR was associated with TSR, and high LMR patients had a 1.4-times higher risk of achieving TSR (95%CI: 1.01-1.99). OS benefit was found with TSR ( P = 0.015) and partial/complete TRG ( P < 0.001). Patients without TSR and with no evidence of pathological response had 2.1-times (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death. CONCLUSION Higher NLR is correlated with longer survival time. High LMR patients have a higher risk of decreasing T stage, whereas high PLR patients have higher odds of progressing under FLOT and dying. Patients with TSR and a pathological response have better OS and lower risk of dying.

Statement of Translational relevanceCetuximab is a highly successful anti-EGFR monoclonal antibody used in the treatment of mCRC patients. However, its low rate of effectiveness suggests mechanisms of resistance so far undefined. Our discoveries identify a new mechanism of cetuximab resistance involving the EGFR effector PLC1 and its interaction with SHP2. Therefore, PLC1 IHC scoring in primary CRC samples identify patients resistant to cetuximab, but who simultaneously benefit from combined inhibition of SHP2 and EGFR. Overall, despite of an improved knowledge about the mechanisms of anti-EGFR therapeutic resistance, this work suggests novel clinical strategies for the treatment of mCRC patients.Research.

There was no heterogeneity between studies (I 2 ¼ 0%; p ¼ 0.6). Conclusions:The response rate to neoadjuvant chemotherapy is very low in MSI-H tumors. MSI status should be considered while deciding for neoadjuvant therapy in locally advanced gastric or gastroesophageal junction cancer. In the MSI-H group, the response rate may increase with the use of immunotherapies in the future.