Revisiting Temozolomide's role in solid tumors: Old is gold?

Temozolomide is an imidazotetrazine with a long history in oncology especially for the high grade malignant glioma and metastatic melanoma. However, last year's new indications for its use are added. Its optimum pharmacodynamic profile, its ability to penetrate the blood-brain barrier, the existence of methylation of MGMT in solid tumors which enhances its efficacy, the identification of new agents that can overcome temozolomide's resistance, the promising role of temozolomide in turning immune cold tumors to hot ones, are leading to expand its use in other solid tumors, giving oncologists an additional tool for the treatment of advanced and aggressive neoplasms.

Transorbital sonography in idiopathic intracranial hypertension: Single-center study, systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) provides a noninvasive tool to detect intracranial pressure by assessing optic nerve sheath diameter (ONSD) and optic disc elevation (ODE). The utility of TOS in the diagnosis of idiopathic intracranial hypertension (IIH) has been increasingly recognized. METHODS: A single-center case-control study sought to compare TOS-acquired ONSD and ODE among IIH-cases versus patients with other neurological diseases (controls). Furthermore, a systematic review and meta-analysis was conducted to present pooled mean differences and diagnostic measures of ONSD and ODE between IIH-cases and controls. RESULTS: In the single-center study, consisting of 31 IIH-cases and 34 sex- and age-matched controls, ONSD values were higher among IIH-cases than controls (p<.001), while ODE was more prevalent in cases (65% vs. 15%; p<.001). The receiver-operating characteristic (ROC)-curve analysis revealed that the optimal cutoff value of ONSD for predicting IIH was 5.15 mm, with an area under the curve (AUC) of 0.914 (95% confidence interval [CI]: 0.861-0.967) and sensitivity and specificity values of 85% and 90%, respectively. In a meta-analysis of 14 included studies with 415 IIH-cases, ONSD and ODE values were higher in IIH-cases than controls (mean difference in ONSD 1.20 mm; 95% CI: 0.96-1.44 mm and in ODE 0.3 mm; 95% CI: 0.33-0.67 mm). With regard to ONSD, pooled sensitivity, specificity, and diagnostic odds ratio were calculated at 85.5% (95% CI: 77.9-90.8%), 90.7% (95% CI: 84.6-94.5%), and 57.394 (95% CI: 24.597-133.924), respectively. The AUC in summary ROC-curve analysis was 0.878 (95% CI: 0.858-0.899) with an optimal cutoff point of 5.0 mm. CONCLUSIONS: TOS has a high diagnostic utility for the noninvasive diagnosis of IIH and may deserve wider implementation in everyday clinical practice.

Is Precision Surgery Applicable to Colorectal Liver Metastases? A Systematic Review and Meta-analysis of Studies that Investigate the Association of Surgical Technique with Outcomes in the Context of Distinct Tumor Biology.

BACKGROUND: Although some data suggest that patients with mutRAS colorectal liver metastases (CRLM) may benefit from anatomic hepatectomy, this topic remains controversial. We performed a systematic review and meta-analysis to determine whether RAS mutation status was associated with prognosis relative to surgical technique [anatomic resection (AR) vs. nonanatomic resection (NAR)] among patients with CRLM. PATIENTS AND METHODS: A systematic review and meta-analysis of studies were performed to investigate the association of AR versus NAR with overall and liver-specific disease-free survival (DFS and liver-specific DFS, respectively) in the context of RAS mutation status. RESULTS: Overall, 2018 patients (831 mutRAS vs. 1187 wtRAS) were included from five eligible studies. AR was associated with a 40% improvement in liver-specific DFS [hazard ratio (HR) = 0.6, 95% confidence interval (CI) 0.44-0.81, p = 0.01] and a 28% improvement in overall DFS (HR = 0.72, 95% CI 0.54-0.95, p = 0.02) among patients with mutRAS tumors; in contrast, AR was not associated with any improvement in liver-specific DFS or overall DFS among wtRAS patients. These differences may have been mediated by the 40% decreased incidence in R1 resection among patients with mutRAS tumors who underwent AR versus NAR [relative risk (RR): 0.6, 95% CI 0.40-0.91, p = 0.02]. In contrast, the probability of an R1 resection was not decreased among wtRAS patients who underwent AR versus NAR (RR: 0.93, 95% CI 0.69-1.25, p = 0.62). CONCLUSIONS: The data suggest that precision surgery may be relevant to CRLM. Specifically, rather than a parenchymal sparing dogma for all patients, AR may have a role in individuals with mutRAS tumors.

Laparoscopic Inguinal Hernia Repair in the Obese Patient Population: A Single-Center Five-Year Experience.

Purpose The objective of the present study is to evaluate the distribution of the transabdominal preperitoneal (TAPP) and the totally extraperitoneal repair (TEP) procedures among the obese and non-obese patient populations, to show how obesity impacts daily practice by reviewing the experience of a single center, and finally, to assess the outcomes of the operations. Methods All patients who underwent elective, minimally invasive inguinal hernia repair in our hospital from January 2017 to January 2022 were included in the present study. The data that were analyzed were patient demographics, each individual patient's American Society of Anesthesiology (ASA) score, the minimally invasive technique (TAPP or TEP) utilized, the body mass index (BMI), and other comorbidities such as underlying diabetes, hypertension, 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 the 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.

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis.

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.

IL-22BP controls the progression of liver metastasis in colorectal cancer.

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown. Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages. Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice. Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC.

Precision Surgery of Colorectal Liver Metastases in the Current Era: A Systematic Review.

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.

The Protective Effect of Bariatric Surgery on the Development of Colorectal Cancer: A Systematic Review and Meta-Analysis.

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.

Demystifying BRAF Mutation Status in Colorectal Liver Metastases : A Multi-institutional, Collaborative Approach to 6 Open Clinical Questions.

OBJECTIVE: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs). BACKGROUND: The clinical implications of mut BRAF status in CRLMs are largely unknown. METHODS: Patients undergoing resection for mut BRAF 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 non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management. RESULTS: A total of 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 with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas 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 with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis. CONCLUSIONS: 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, second 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 non-V600E mutations have excellent prognosis.

Colorectal Surgery in the COVID-19 Era: A Systematic Review and Meta-Analysis.

(1) Background: To determine the impact of the COVID-19 pandemic in the management of colorectal cancer patients requiring surgery and to examine whether the restructuring of healthcare systems led to cancer stage upshifting or adverse treatment outcomes; (2) Methods: A systematic literature search of the MedLine, Scopus, Web of Science, and CNKI databases was performed (PROSPERO ID: CRD42021288432). Data were summarized as odds ratios (OR) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs); (3) Results: Ten studies were examined, including 26,808 patients. The number of patients presenting with metastases during the pandemic was significantly increased (OR 1.65, 95% CI 1.02−2.67, p = 0.04), with no differences regarding the extent of the primary tumor (T) and nodal (N) status. Patients were more likely to have undergone neoadjuvant therapy (OR 1.22, 95% CI 1.09−1.37, p < 0.001), while emergency presentations (OR 1.74, 95% CI 1.07−2.84, p = 0.03) and palliative surgeries (OR 1.95, 95% CI 1.13−3.36, p = 0.02) were more frequent during the pandemic. There was no significant difference recorded in terms of postoperative morbidity; (4) Conclusions: Patients during the pandemic were more likely to undergo palliative interventions or receive neoadjuvant treatment.

Reevaluating the prognostic role of BRAF mutation in colorectal cancer liver metastases.

INTRODUCTION: Mutations in the BRAF proto-oncogene have been shown to predict poor patient survival following curative-intent liver surgery for metastatic colorectal cancer. The aim of the present systematic review and meta-analysis is to evaluate the effect of mutated BRAF status (mutBRAF) on the overall (OS) and disease-free survival (DFS) in these patients. METHODS: A comprehensive literature search was performed for studies reporting outcomes of patients undergoing curative-intent surgery stratified by BRAF mutation status. Subgroup analysis was performed to evaluate whether inclusion of KRAS mutation status significantly influenced the results. RESULTS: Six studies incorporating 1857 patients with known BRAF status were identified. Pooled results revealed significantly worse OS (Hazard Ratio 2.8, 95% C.I. 2.09 to 3.77) and DFS (Hazard Ratio 2.29, 95% C.I. 2.09 to 3.77) in mutBRAF patients. Subgroup analysis revealed no statistically significant impact of including KRAS status testing on the obtained results. CONCLUSIONS: Patients with metastatic colorectal cancer carrying BRAF mutations have significantly worse oncologic outcomes following surgery and more aggressive disease phenotype overall.

Appraisal of a Contact Tracing Training Program for COVID-19 in Greece Focusing on Vulnerable Populations.

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.

p53 protein expression in synchronously occurring dedifferentiating stages of thyroid cancer in a patient with neurofibromas: A case report.

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.

Rescue medical activities among sea migrants and refugees in the Mediterranean region: lessons to be learned from the 2014-2020 period.

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.

Reevaluating the prognostic value of RAS mutation status in patients with resected liver metastases from colorectal cancer: A systematic review and meta-analysis.

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.

The interplay of KRAS mutational status with tumor laterality in non-metastatic colorectal cancer: An international, multi-institutional study in patients with known KRAS, BRAF, and MSI status.

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.

The Interplay Between Innate Immunity (TLR-4) and sCD40L in the Context of an Animal Model of Colitis-associated Cancer.

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.

Platelet Depletion/Transfusion as a Lethal Factor in a Colitis-associated Cancer Mouse Model.

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.

Cross-sectional study on awareness and knowledge of torture investigation and documentation among Greek doctors and senior medical students.

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.

Time to Rethink Refugee and Migrant Health in Europe: Moving from Emergency Response to Integrated and Individualized Health Care Provision for Migrants and Refugees.

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.