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Background: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. Methods: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. Results: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p >.05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p =.004; RFS: 68.8% vs. 77.3%, p =.005) and multivariable analysis (OS: HR: 1.52, p =.019; RFS: HR: 1.32, p =.05). Conclusions: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

Background/aim Several studies have found elevated soluble CD40 Ligand (sCD40L) in the serum of patients with malignancies as well as those with inflammatory bowel disease (IBD). Our goal was to determine the possible causal role of sCD40L in colitis-associated colorectal cancer (CAC) by using the well-established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Materials and methods Twelve wild type (WT) and twelve TLR4 knock out (KO) female C57BL6 mice were divided into 4 experimental groups. Six WT and six TLR4 KO mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 7-day cycles of oral 2.5% DSS. The other two groups included 6 WT and 6 TLR4 KO mice that received only water and served as the control groups. The mice were sacrificed after 84 days. Results All mice in the AOM/DSS WT group developed CAC while all mice from the AOM/DSS TLR4 KO group were protected from CAC. We measured the serum and pathologic tissue levels of sCD40L with quantitative sandwich enzyme-linked immunoassay (ELISA) and found that serum sCD40L was significantly higher in wild-type mice that developed CAC compared to their healthy counterparts (wild-type and TLR-4 KO controls). In comparison, serum sCD40L levels were comparable between TLR-4 KO mice, which are protected from developing CAC, and their healthy counterparts (wild-type and TLR-4 KO controls). Of note, tissue levels of sCD40L were not affected by the development of CAC. Conclusion Our findings point to the presence of an axis between TLR-4 and sCD40L, which may lead to decreased immunosurveillance and the subsequent development of colitis-associated cancer.

Background: Contact tracing as an epidemiological strategy has repeatedly contributed to the containment of various past epidemics and succeeded in controlling the spread of disease in the community. Systematic training of contact tracers is crucial in ensuring the effectiveness of epidemic containment. Methods: An intensive training course was offered to 216 health and other professionals who work with vulnerable population groups, such as Roma, refugees, and migrants in Greece, by the scientific team of the postgraduate programme “Global Health-Disaster Medicine” of the Medical School, National and Kapodistrian University of Athens, with the support of the Swiss embassy in Greece. The course was delivered online due to the pandemic restriction measures and was comprised of 16 h over 2 days. The course curriculum was adapted in Greek using, upon agreement, a similar training course to what was developed by the Johns Hopkins University Bloomberg School of Public Health. Evaluation of the course was conducted in order to determine the short term satisfaction from participating in this training course. Results: A total of 70% of the course participants completed the evaluation questionnaires and all trainers gave feedback on the course. The training modules were ranked as extremely useful by the majority of the participants and over 50% of the participants specifically stated that the course content was directly related to their work with vulnerable groups. Content about the ethics of contact tracing and the effective communication skills presented were deemed most useful. Conclusion: The course was well organised and provided the required skills for effective contact tracing. Many course participants intend to use some components in their work with vulnerable populations groups. Contact tracing efforts work best in a systematic and coordinated way and the provision of systematic and organised training can greatly increase its effectiveness.

Background/aim TLR-4 Knock-out (KO) mice are protected from colitis-associated cancer in the established AOM/DSS mouse model. The aim of this study was to assess whether the TLR4 KO mice would still be protected from carcinogenesis after platelet depletion and transfusion with TLR4 wild-type platelets. Materials and methods Thirty-two female C57BL6 mice were divided into 6 groups. Among the three groups that received Azoxymethane/Dextran Sulfate Sodium (AOM/DSS), one group included TLR4KO mice, which were depleted of their platelets and were then transfused with platelets from TLR4 wild-type mice. The other two groups included wild-type and TLR-4KO mice that only received AOM/DSS. Results All 6 animals in the KO group that underwent platelet depletion/transfusion succumbed. Three of them died before the administration of DSS and three in the week following DSS administration. In contrast, mice in the other two groups experienced less weight loss and only 1 mouse died in each of them. Conclusion Platelet depletion/transfusion was detrimental in TLR-4 transgenic mice that received AOM/DSS.

BACKGROUND Although the value of Rat Sarcoma Oncogene (RAS) mutation status in predicting long-term outcomes in patients with colorectal liver metastases (CRLM) is widely accepted, the magnitude of its impact has recently been challenged by three large cohort studies. The aim of this meta-analysis is to reevaluate the impact of RAS mutations on overall survival (OS) and disease-free survival (DFS) in patients who underwent curative-intent resection of CRLM. METHODS A comprehensive literature search was performed for studies reporting outcomes of patients undergoing curative-intent surgery stratified by RAS mutation status. Exclusion criteria were defined a priori. Subgroup analysis was performed to evaluate the effect of publication date, sample size, and KRAS vs any RAS mutation on overall outcomes. RESULTS Ten studies incorporating 3115 patients with known RAS status were identified. Pooled results revealed significantly worse OS (Hazard Ratio 1.5, 95% CI 1.31-1.71) and DFS (Hazard Ratio 1.36, 95% CI 1.22-1.52) in RAS-mutated patients. Subgroup analyses revealed that studies including more than 300 patients or published after 2015 reported lower HR than their counterparts. CONCLUSION The results of this meta-analysis suggest that the prognostic value of RAS mutation status in patients with CRLM has been previously overestimated.

Background: Since 2014, the number of migrants and refugees crossing the Mediterranean towards Europe has risen significantly due to various reasons. Both state agencies and non-governmental organizations (NGOs) have launched rescue missions in the Central Mediterranean in accordance with international legal obligations for search and rescue (SAR) operations for those under distress at sea. Our aim is to summarise the specific qualifications needed for maritime SAR in the Mediterranean both in terms of the population at risk, the equipment and the medical support required, especially during the coronavirus disease 2019 (COVID-19) pandemic and the operational legal framework. Materials and methods: This article aims to summarise the key points of SAR efforts from a medical perspective as depicted in the relevant literature during a specific timeline period (2014-2020) in a specific part of the Mediterranean Sea (Central Mediterranean route). Only papers published in English and whose full text was available were included in this study. The inclusion criteria were: a) articles referring to sea rescue operations between 2014 and 2020, b) research that focused on medical preparedness and assistance during rescue operations in the Central Mediterranean route, c) studies concerning demographic and clinical features of the rescue population, d) guidelines on the rule of conduct of persons and states participating in rescue activities. The exclusion criteria were: a) studies describing SAR operations in different regions of the world and b) studies focusing on routes, demographics and medical support of migrants/refugees on land. Results: Three major themes were identified: a) characteristics of the population in distress at sea: country of origin, age groups, presence of communicable and non-communicable diseases were identified in the relevant literature. Our research shows that dermatological and respiratory issues were the major concerns among sea migrants, coming from different countries of both Africa and Asia, being relatively young and mostly males; b) medical preparedness and equipment needed for rescue: according to current guidelines, revised during the COVID-19 pandemic, infrastructure needed during SAR operations includes both equipment for resuscitation, personal protective equipment, deck adjustments, medical personnel trained to function in an austere setting and able to handle vulnerable patient groups such as children and pregnant women; c) medico-legal implications of SAR operations: knowledge of the legal framework encompassing SAR operations seems necessary, as European Union and state led initiatives seem to withdraw from proactive SAR, while criminalising NGO led rescue efforts. Operating with the imperative to save lives seems to be the only way of respecting international law and human values, thus, a summary of what the law dictates was made in an effort to keep medical workers participating in such operations updated. Conclusions: Investigation aims to shed light on the special clinical features of sea migrants, the skills, equipment and organizational structure needed by medical workers participating in SAR operations as well as the legal framework under which they will be asked to operate. Special consideration will be given to the difficulties that emerged due to the COVD-19 pandemic.

In the last three years, the European Union (EU) is being confronted with the most significant influx of migrants and refugees since World War II. Although the dimensions of this influx—taking the global scale into account—might be regarded as modest, the institutional response to that phenomenon so far has been suboptimal, including the health sector. While inherent challenges of refugee and migrant (R&M) health are well established, it seems that the EU health response oversees, to a large extend, these aspects. A whole range of emergency-driven health measures have been implemented throughout Europe, yet they are failing to address adequately the changing health needs and specific vulnerabilities of the target population. With the gradual containment of the migratory and refugee waves, three years after the outbreak of the so-called ‘refugee crisis’, we are, more than ever, in need of a sustainable and comprehensive health approach that is aimed at the integration of all of migrants and refugees—that is, both the new and old population groups that are already residing in Europe—in the respective national health systems.

Doctors in Greece face the possibility of encountering a person that has suffered torture, especially since the high rates of refugees’ and migrants’ inflows that took place over the last years. In order to assess the awareness and the knowledge of doctors and senior medical students in Greece regarding a manual on effective investigation and documentation of torture such as Istanbul Protocol (official United Nation document since 1999), a cross-sectional study was conducted using a structured anonymous questionnaire. The sample was doctors practicing in public hospitals in Greece, doctors volunteering at a non-governmental organization (NGO) and undergraduate medical students in their final year of studies in the Medical School of National and Kapodistrian University of Athens. The data were analyzed using IBM SPSS version 23, using descriptive statistics and statistical significance tests. In a total of 289 participants, the mean total score of Istanbul Protocol knowledge was 4.43 ± 1.104 (the maximum possible score was 10) and the mean total score of Istanbul Protocol awareness was 2.04 ± 1.521 (the maximum possible score was 10). The most important conclusion was that among doctors and senior medical students, there seem to be knowledge, awareness, and information deficit about Istanbul Protocol and several issues relating to torture. The overall research outcome highlights the need for the development of a relevant informative/educational program, in order to cover the corresponding existing needs of the population of doctors in Greece.