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To investigate the clinical implications of BRAF mutated (mutBRAF) colorectal liver metastases (CRLM).The clinical implications of mutBRAF status in CRLM are largely unknown.Patients undergoing resection for mutBRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus nonV600E mutations, KRAS/BRAF co-mutation versus mutBRAF alone, MSS versus MSI status, upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy (RH) versus non-operative management.240 patients harboring BRAF-mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs. 144 mo, P=0.004), but not RFS compared to nonV600E mutations. KRAS/BRAF co-mutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs. 26 mo, P0.001) but not OS (33.5 vs. 41 mo, P=0.3) compared to MSI-high tumors, while patients with resected converted disease had slightly worse RFS (8 vs. 11 mo, P=0.01) and similar OS (30 vs. 40 mo, P=0.4) compared to those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared to those with liver-limited disease (8.8 vs. 40 mo, P0.001). RH following intrahepatic recurrence was associated with improved OS compared to non-operative management (41 vs. 18.7 mo, P=0.004). All results continued to hold true in the multivariable OS analysis.Although surgery may be futile in patients with BRAF-mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, repeat hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group with regard to RFS while patients with nonV600E mutations have excellent prognosis.

Purpose: The purpose of the present study is to explore how obesity impacts daily practice by reviewing the experience of a single-center, to evaluate the distribution of the TAPP and TEP methods amongst obese and non-obese patient populations and assess relevant postoperative outcomes.Methods: patients undergoing elective minimally invasive inguinal hernia repair in our hospital, were included from January 2017 to January 2022. Data of interest were the minimally invasive technique utilized, patient demographics, individual patient American Society of Anesthesiology (ASA) score, the body mass index (BMI), underlying hypertension and diabetes, and smoking status.Results: A total of 109 patients were included in the present analysis, of which 81 (74.3%) underwent elective TEP repairs, while 28 (25.7%) underwent elective TAPP repairs. Overall, 39 (35.7%) patients were included in the obesity subgroup with an average BMI of 35.4 ± 4.9, with a range from 30,1 to 52,7, and 70 (64.3%) were included in the non-obese subgroup, with an average BMI of 23.2 ± 3.3 and a range from 16,2 to 29,7.Conclusions: The laparoscopic approach to inguinal hernia repair in obese patients has similar outcomes as an open approach regarding the 30-day events, in the hands of experienced surgeons with the advantages of the laparoscopic approach vs. the open one.

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.

Liver resection for colorectal liver metastases (CRLM) is widely considered the treatment with the highest curative potential. However, not all patients derive the same oncological benefit, underlining the need for better patient stratification and treatment allocation. In this context, we performed a systematic review of the literature to determine the role of RAS status in selecting the optimal surgical strategy. Evidence comparing anatomical with non-anatomical resections depending on RAS mutational status was scarce and conflicting, with two studies reporting superiority in mutated RAS (mutRAS) patients and two studies reporting equivalent outcomes. The rate of incomplete microscopic resection (R1) was found to be increased among mutRAS patients, possibly due to higher micrometastatic spread lateral to the primary lesion. The impact of R1 resection margins was evaluated separately for mutRAS and wild-type patients in three studies, of which, two indicated an additive detriment to long-term survival in the former group. In the current era of precision surgery, RAS status can be utilized to predict the efficacy of liver resection in the treatment of CRLM, avoiding a potentially morbid operation in patients with adverse tumor profiles.

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: Obesity is a known risk factor for developing colorectal cancer (CRC) and is associated with the formation of precancerous colonic adenomas. Bariatric surgery (BRS) is considered to reduce the cancer risk in morbidly obese patients. However, the currently available literature yields contradicting results regarding the impact of bariatric surgery on the incidence of CRC. Methods: A systematic literature search of the Medline, Embase, CENTRAL, CINAHL, Web of Science, and clinicaltrials.gov databases was undertaken following the PRISMA guidelines. A random effects model was selected. Results: Twelve retrospective cohort studies, incorporating a total of 6,279,722 patients, were eligible for inclusion in the final quantitative analysis. Eight studies originated from North America, while four reported on European patients. Patients in the Bariatric Surgery group exhibited a significantly reduced risk for developing colorectal cancer (RR 0.56, 95% CI 0.4–0.8, p < 0.001), while sleeve gastrectomy was found to be significantly associated with a smaller incidence of CRC (RR 0.55, 95% CI 0.36–0.83, p < 0.001), and gastric bypass and banding did not. Conclusions: A significant protective effect of BRS against the development of CRC is implied. In the present analysis, the incidence rate of colorectal cancer was approximately halved amongst the obese individuals that were operated on.

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) have been hypothesized to arise from well-differentiated thyroid carcinoma (WDTC) due to frequently reported synchronous and metachronous occurrence. Loss of normal p53 function has been implicated in this dedifferentiation process. The current case report presents a 60-year-old male with multiple neurofibromas who underwent total thyroidectomy due to multiple palpable thyroid nodules. Histopathological examination revealed three foci of predominantly papillary, but also follicular carcinoma growth pattern, and two lesions with histological features of insular and trabecular variant, with the larger one showing foci of anaplastic transition. Nuclear p53 protein accumulation, corresponding to mutant abnormally stabilized p53, was higher in more aggressive variants compared with WDTC. The somatic molecular events and downstream pathways of this dedifferentiation course have not been unraveled yet. The present case report demonstrated the simultaneous presence of three divergent histological subtypes in a single thyroid gland, with progressive enhancement of nuclear p53 protein expression, associated with mutant p53 protein, in the more aggressive variants. This is a rare case of progressive enhancement of mutant nuclear p53 protein expression in multifocal thyroid tumor areas consisting of WDTC, PDTC and ATC histological types, highlighting the possibility that WDTC can progress to PDTC and then ATC through an intricate procedure, involving loss of normal p53 function.

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.

Natural catastrophes are disastrous phenomena leaving behind multiple casualties. Among natural disasters with the highest impact on human habitat are the earthquakes, tsunamis, volcanos, floods, storms, and wildfires. Disaster medical teams respond to these major incidents applying an all hazard approach while cooperating with all responsible stakeholders. Effective medical care is of paramount importance taking under consideration the short- as well as long-term needs of the affected population. The effectiveness of medical care depends on the continuity of actions and interventions from prehospital area to the in-hospital setting. Although natural disasters cannot be always prevented, a scholastic preparation, systematic approach and prompt medical care can minimize their burden on health.

Disasters occur much more frequently in the last 20 years with the majority of them in middle-low-income countries. The main causes are overpopulation, urbanization, poverty, and unhealthy living conditions and climate change. The definition of disaster for a specific community always incorporates its inability to manage the situation on its own means. A multi-casualty incident (MCI) becomes a disaster for a specific area and time when we are unable to provide effective therapy to the victims. Training in disaster management is required and directly concerned with health professionals. Worldwide, emergency medicine as a medical specialty dedicates a large portion of its educational curriculum specifically to disaster medicine. The handling of a disaster demands that healthcare personnel are incorporated into non-medical multidiscipline response teams, and this fact highlights the necessity of performing combined simulation exercises. Disaster can have a major impact on public health systems. The destruction of healthcare facilities, for example, impedes us from providing immediate and also subsequent medical care. Taking measures to reduce the disaster risk is a cost-effective investment in order to avoid future losses and the existence of a disaster emergency plan is required both at national and local levels. Disaster in a certain place has consequences on other places of our planet (immigration, epidemics). The need to take preventive measures and to offer assistance, especially in developing countries, has become recognized worldwide.

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.

The advent of both natural and manmade disasters is increasingly highlighting the role of citizens (ranging from spontaneous volunteers and first responders to emergent entities and communities of civic action) as inevitable and potentially valuable resource in their management.

Background Despite recent advances the pathogenesis of Crohn's disease remains incompletely understood. A variety of animal models have been utilized in an effort to provide further insights and develop more therapeutic options. In order to simulate, to an extent, the pathogenesis and the clinical course of the disease, TNBS induced colitis is often used. Various approaches for inducing TNBS -colitis have been described in the literature. Methods/results In this review, we sought to present the animal model of TNBS induced colitis and outline the pathogenesis, pathophysiology, clinical course and pathological characteristics of the model. Furthermore, we describe the differences among those protocols regarding types of animals and colitis induction. Data sources The MEDLINE database was thoroughly searched using the keywords: TNBS, colitis, Crohn's disease, animal model. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Additional articles were gathered and evaluated. Conclusion The aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers., Highlights • We sought to present the animal model of TNBS induced colitis and outline the pathogenesis, pathophysiology, clinical course and pathological characteristics of the model. • Furthermore, we describe the differences among those protocols regarding types of animals and colitis induction. • The MEDLINE database was thoroughly searched using the keywords: TNBS, colitis, Crohn's disease, animal model. • Two investigators independently reviewed the abstracts and appropriate articles were included in this review. • The aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers.

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.

Early management of vascular injury, starting at the field, is imperative for survival no less than any operative maneuver. Contemporary prehospital management of vascular trauma, including appropriate fluid and volume infusion, tourniquets, and hemostatic agents, has reversed the historically known limb hemorrhage as a leading cause of death. In this context, damage control (DC) surgery has evolved to DC resuscitation (DCR) as an overarching concept that draws together preoperative and operative interventions aiming at rapidly reducing bleeding from vascular disruption, optimizing oxygenation, and clinical outcomes. This review addresses contemporary DCR techniques from the prehospital to the surgical setting, focusing on civilian vascular injuries.