The introduction of KRAS testing as a diagnostic tool to select patients for epidermal growth factor receptor (EGFR)-targeted cetuximab- or panitumumab-based therapies for metastatic colorectal cancer is widely regarded as a key advance in the field of personalized cancer medicine. Oncologists are now facing emerging issues in the treatment of metastatic colorectal cancer, including: (i) the identification of additional genetic determinants of primary resistance to EGFR-targeted therapy for further improving selection of patients; (ii) the explanation of rare cases of patients carrying KRAS-mutated tumors who have been reported to respond to either cetuximab or panitumumab and (iii) the discovery of mechanisms of secondary resistance to anti-EGFR antibody therapies. Here we discuss the potential role of comprehensive dissection of the key oncogenic nodes in the EGFR signaling cascade to predict resistance and sensitivity to EGFR monoclonal antibodies in metastatic colorectal cancer. Current data suggest that, together with KRAS mutations, the evaluation of BRAF and PIK3CA/PTEN alterations could also be useful for selecting patients with reduced chance to benefit from EGFR-targeted therapy. Furthermore, measuring EGFR gene copy number also appears relevant to positively identify responders. Up until now, each of these markers has been mainly assessed as a single event, often in retrospective analyses and patients' series. As these molecular alterations display overlapping patterns of occurrence, this adds considerable complexity to the drawing of an algorithm suitable for clinical decision-making. We suggest that in the near future comprehensive molecular analysis of the entire oncogenic pathway triggered by the EGFR should be performed, thus enhancing the prediction ability of individual markers.
Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62–80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5–270) minutes vs. 190 (IQR 150–245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82–13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10–0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04–4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85–14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10497-7.
The aim of this study i.e., is to present the distribution of traumatic dental injuries (TDI) in 306 patients registered at the Unit of Dental Emergencies at a University Dental Clinic in Milan, Italy, between June 2019 and May 2021. This time frame includes the beginning of the SARS-CoV-2 pandemic. Information regarding age, gender, number and type of injured teeth, type of traumatic injury, and data on where or how the injury happened were recorded. Seventy-nine percent of patients can be classified as pediatric (under 14 years old), and in all age groups, male patients were found to be more susceptible (1.6:1). A total of 480 teeth were involved, 59% of which were deciduous, and 41% permanent. The most affected teeth in both dentitions were upper central incisors. In deciduous teeth, periodontal lesions were more common, whereas in permanent dentitions, dental fractures were diagnosed more often. Most data found in this study confirms the results found in the literature. The biggest difference, due to changes in daily routine during the SARS-CoV-2 pandemic, can be found by analyzing the incidence and etiology. As a matter of fact, there was a decrease in school accidents, whereas domestic falls remained constant.
Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the 10 centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients (median age, 74 [interquartile range (IQR), 62–80.75] years; males, 154 [52.0%]; 34 [11.5%] COVID-19) qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group (230 [IQR, 200.5–270] minutes vs 190 [IQR, 150–245] minutes; p=0.007), especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤50% of the occluded territory (50.0% vs 16.6%; OR, 5.05; 95% CI, 1.82–13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs 81.0%; OR, 0.29; 95% CI, 0.10–0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs 19.5%; OR, 2.24; 95% CI, 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs 8.8%; OR, 6.43; 95% CI, 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.
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