In gastric cancer (GC), epidermal growth factor receptor (EGFR) overexpression associates with poor prognosis. Addition of a chimeric monoclonal antibody against EGFR (cetuximab) to first-line treatment of metastatic colorectal tumours improved outcomes of patients (stratified for KRAS wild-type cancers), whereas GC patients did not benefit from this approach. In GC, however, stratification based on KRAS mutations was not performed, and the 30 % KRAS mutation frequency in microsatellite instable cancers (MSI), which represents ∼4 % of total GC, was disregarded. Further, intratumoural heterogeneity regarding KRAS mutant subpopulations might also contribute to anti-EGFR therapy failure. We assessed the mutational status of the entire KRAS coding sequence in 19 MSI-GC cases by multiplex PCR/sequencing and used peak height ratio determined from electropherograms from KRAS heterozygous mutants and histopathological evaluation to infer tumour heterogeneity in GC. Using 2 multiplex reactions per sample, we found that 26 % (5/19) of MSI-GC cases harboured KRAS mutations (2 G12D, 2 G13D, 1 G12V). No mutations were found outside the codon 12 and 13 hotspots. Our analysis supported the co-existence of KRAS-positive and KRAS-negative tumour populations in 4/5 MSI-GC cases. In conclusion, the method developed stands as a cost-effective and practical way for mutation screening of the entire KRAS coding sequence. KRAS mutations are frequent in our series of MSI cases and are often found in a subpopulation of the tumour and not in the whole tumour. Further studies are needed to access the implications of this heterogeneity in KRAS mutant and wild-type tumour clones in anti-EGFR therapy response.

Introduction and objectives The coronavirus disease 2019 (COVID-19) spread quickly around the world. Although mainly a respiratory illness, there is growing interest in non-respiratory manifestations, particularly cardiovascular ones. At our center, mobilization of cardiologists with intensive care training was needed. Our aim is to describe patients with severe COVID-19 admitted to a Portuguese intensive care unit (ICU), the cardiovascular impact of the disease and the experience of cardiologists working in a COVID-19 ICU. Methods Data from adult patients with COVID-19 admitted to the ICU of Centro Hospitalar de Vila Nova de Gaia/Espinho between 16 March 2020 and 21 April 2020 were analyzed retrospectively. Results Thirty-five patients were admitted. Mean age was 62.6±6.0 years and 23 (65.7%) were male. Dyslipidemia was the most common cardiovascular risk factor (65.7%, n=23), followed by hypertension (57.1%, n=20). Mean ICU stay time was 15.9±10.0 days. Patients had high rates of mechanical ventilation (88.6%, n=31) and vasopressor support (88.6%, n=31). Low rates of new onset left systolic dysfunction were detected (8.5%, n=2). One patient required venoarterial extra-corporeal membrane oxygenation. Mortality was 25% (n=9). Acute myocardial injury and N-terminal pro-B-type natriuretic peptide (NT-proBNP) elevation was detected in 62.9% (n=22). Patients that died had higher NT-proBNP compared to those discharged alive (p<0.05). Care by cardiologists frequently changed decision making. Conclusions The cardiovascular impact of COVID-19 seems relevant but is still widely unknown. Studies are needed to clarify the role of cardiac markers in COVID-19 prognosis. Multidisciplinary care most likely results in improved patient care.

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Introduction The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) to support patients in cardiogenic shock has been increasing in Portugal over the past few years. Nonetheless, epidemiologic, prognostic and clinical outcome data are scarce. Purpose We aim to identify clinical variables with prognostic significance in this challenging population, as well as the performance of various risk scores in mortality prediction. Methods All patients that underwent VA-ECMO support at our Cardiac ICU between 2011 and 2018 were included in the analysis. Logistic regression analysis was used to assess the relationship between clinical variables and outcomes. Results Short-term mechanical support with VA-ECMO was given to 40 patients, with a mean age of 52±11 years. At the time of the implant, the mean SOFA score was 11.2±4.0, and mean SAVE score was −4.75±4.6. Mean ECMO support duration was 116±96 hours. In 70% (N=28) of patients, VA-ECMO was successfully weaned. In-hospital mortality was observed in 52.5% of patients, which was in accordance with the predicted mortality by SOFA score (22.5% to 82% in our population risk range) and by SAVE score (60 to 70%). Those who placed the VA-ECMO as a bridge to transplant or to long-term mechanical LV assist device had greater in-hospital mortality rates (91.6 vs 41.9%, p=0.013), as well as those under ≥2 inotropic/vasopressors (69.2 vs 21.4%, p=0.012) or when adrenaline use was needed (100% vs 44.1%, p=0.01). No other between-group differences were observed in what concerns short-term mortality. After logistic regression analysis, independent predictors of in-hospital mortality included AMI setting, number of vasoactive amines used, and necessity of a LV venting device. SAVE score had the greater predictive ability in these patients (AUC = 0.638) among the most utilized clinical risk scores (SOFA score AUC = 0.37; APACHE II score AUC = 0.59; SAPS II score AUC = 0.54). Conclusion In our analysis, patients in profound cardiogenic shock on VA-ECMO support had slightly better survival rates than predicted by classical Risk Scores. The SAVE score may be the most accurate tool to predict in-hospital mortality in this specific, and yet heterogeneous, clinical subset. Other well recognized clinical markers of severity may also help refine short-term prognosis, and potentially improve organ transplant or other destination therapy prioritization.