European University Cyprus

Raine T., Bonovas S., Burisch J., Kucharzik T., Adamina M., Annese V., Bachmann O., Bettenworth D., Chaparro M., Czuber-Dochan W., Eder P., Ellul P., Fidalgo C., Fiorino G., Gionchetti P., et. al.

Wenning G.K., Stankovic I., Vignatelli L., Fanciulli A., Calandra‐Buonaura G., Seppi K., Palma J., Meissner W.G., Krismer F., Berg D., Cortelli P., Freeman R., Halliday G., Höglinger G., Lang A., et. al.

The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology.We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Olasveengen T.M., Semeraro F., Ristagno G., Castren M., Handley A., Kuzovlev A., Monsieurs K.G., Raffay V., Smyth M., Soar J., Svavarsdottir H., Perkins G.D.

Abstract The European Resuscitation Council has produced these basic life support guidelines, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include cardiac arrest recognition, alerting emergency services, chest compressions, rescue breaths, automated external defibrillation (AED), CPR quality measurement, new technologies, safety, and foreign body airway obstruction.

Gloster A.T., Lamnisos D., Lubenko J., Presti G., Squatrito V., Constantinou M., Nicolaou C., Papacostas S., Aydın G., Chong Y.Y., Chien W.T., Cheng H.Y., Ruiz F.J., Garcia-Martin M.B., Obando-Posada D.P., et. al.

Background The COVID-19 pandemic triggered vast governmental lockdowns. The impact of these lockdowns on mental health is inadequately understood. On the one hand such drastic changes in daily routines could be detrimental to mental health. On the other hand, it might not be experienced negatively, especially because the entire population was affected. Methods The aim of this study was to determine mental health outcomes during pandemic induced lockdowns and to examine known predictors of mental health outcomes. We therefore surveyed n = 9,565 people from 78 countries and 18 languages. Outcomes assessed were stress, depression, affect, and wellbeing. Predictors included country, sociodemographic factors, lockdown characteristics, social factors, and psychological factors. Results Results indicated that on average about 10% of the sample was languishing from low levels of mental health and about 50% had only moderate mental health. Importantly, three consistent predictors of mental health emerged: social support, education level, and psychologically flexible (vs. rigid) responding. Poorer outcomes were most strongly predicted by a worsening of finances and not having access to basic supplies. Conclusions These results suggest that on whole, respondents were moderately mentally healthy at the time of a population-wide lockdown. The highest level of mental health difficulties were found in approximately 10% of the population. Findings suggest that public health initiatives should target people without social support and those whose finances worsen as a result of the lockdown. Interventions that promote psychological flexibility may mitigate the impact of the pandemic.

Di Lorenzo N., Antoniou S.A., Batterham R.L., Busetto L., Godoroja D., Iossa A., Carrano F.M., Agresta F., Alarçon I., Azran C., Bouvy N., Balaguè Ponz C., Buza M., Copaescu C., De Luca M., et. al.

Surgery for obesity and metabolic diseases has been evolved in the light of new scientific evidence, long-term outcomes and accumulated experience. EAES has sponsored an update of previous guidelines on bariatric surgery. A multidisciplinary group of bariatric surgeons, obesity physicians, nutritional experts, psychologists, anesthetists and a patient representative comprised the guideline development panel. Development and reporting conformed to GRADE guidelines and AGREE II standards. Systematic review of databases, record selection, data extraction and synthesis, evidence appraisal and evidence-to-decision frameworks were developed for 42 key questions in the domains Indication; Preoperative work-up; Perioperative management; Non-bypass, bypass and one-anastomosis procedures; Revisional surgery; Postoperative care; and Investigational procedures. A total of 36 recommendations and position statements were formed through a modified Delphi procedure. This document summarizes the latest evidence on bariatric surgery through state-of-the art guideline development, aiming to facilitate evidence-based clinical decisions.

Neophytou C.M., Panagi M., Stylianopoulos T., Papageorgis P.

The tumor microenvironment (TME) regulates essential tumor survival and promotion functions. Interactions between the cellular and structural components of the TME allow cancer cells to become invasive and disseminate from the primary site to distant locations, through a complex and multistep metastatic cascade. Tumor-associated M2-type macrophages have growth-promoting and immunosuppressive functions; mesenchymal cells mass produce exosomes that increase the migratory ability of cancer cells; cancer associated fibroblasts (CAFs) reorganize the surrounding matrix creating migration-guiding tracks for cancer cells. In addition, the tumor extracellular matrix (ECM) exerts determinant roles in disease progression and cancer cell migration and regulates therapeutic responses. The hypoxic conditions generated at the primary tumor force cancer cells to genetically and/or epigenetically adapt in order to survive and metastasize. In the circulation, cancer cells encounter platelets, immune cells, and cytokines in the blood microenvironment that facilitate their survival and transit. This review discusses the roles of different cellular and structural tumor components in regulating the metastatic process, targeting approaches using small molecule inhibitors, nanoparticles, manipulated exosomes, and miRNAs to inhibit tumor invasion as well as current and future strategies to remodel the TME and enhance treatment efficacy to block the detrimental process of metastasis.

Georgakopoulos-Soares I., Chartoumpekis D.V., Kyriazopoulou V., Zaravinos A.

The epithelial-mesenchymal transition (EMT) represents a biological program during which epithelial cells lose their cell identity and acquire a mesenchymal phenotype. EMT is normally observed during organismal development, wound healing and tissue fibrosis. However, this process can be hijacked by cancer cells and is often associated with resistance to apoptosis, acquisition of tissue invasiveness, cancer stem cell characteristics and cancer treatment resistance. It is becoming evident that EMT is a complex, multifactorial spectrum, often involving episodic, transient or partial events. Multiple factors have been causally implicated in EMT including transcription factors (e.g., SNAIL, TWIST, ZEB), epigenetic modifications, microRNAs (e.g., miR-200 family) and more recently, long non-coding RNAs. However, the relevance of metabolic pathways in EMT is only recently being recognized. Importantly, alterations in key metabolic pathways affect cancer development and progression. In this review, we report the roles of key EMT factors and describe their interactions and interconnectedness. We introduce metabolic pathways that are involved in EMT, including glycolysis, the TCA cycle, lipid and amino acid metabolism, and characterize the relationship between EMT factors and cancer metabolism. Finally, we present therapeutic opportunities involving EMT, with particular focus on cancer metabolic pathways.

Neophytou C.M., Trougakos I.P., Erin N., Papageorgis P.

The ability of tumor cells to evade apoptosis is established as one of the hallmarks of cancer. The deregulation of apoptotic pathways conveys a survival advantage enabling cancer cells to develop multi-drug resistance (MDR), a complex tumor phenotype referring to concurrent resistance toward agents with different function and/or structure. Proteins implicated in the intrinsic pathway of apoptosis, including the Bcl-2 superfamily and Inhibitors of Apoptosis (IAP) family members, as well as their regulator, tumor suppressor p53, have been implicated in the development of MDR in many cancer types. The PI3K/AKT pathway is pivotal in promoting survival and proliferation and is often overactive in MDR tumors. In addition, the tumor microenvironment, particularly factors secreted by cancer-associated fibroblasts, can inhibit apoptosis in cancer cells and reduce the effectiveness of different anti-cancer drugs. In this review, we describe the main alterations that occur in apoptosis-and related pathways to promote MDR. We also summarize the main therapeutic approaches against resistant tumors, including agents targeting Bcl-2 family members, small molecule inhibitors against IAPs or AKT and agents of natural origin that may be used as monotherapy or in combination with conventional therapeutics. Finally, we highlight the potential of therapeutic exploitation of epigenetic modifications to reverse the MDR phenotype.

Antoniou G.A., Antoniou S.A., Torella F.

Objective The objective was to investigate whether endovascular aneurysm repair (EVAR) has better peri-operative and late clinical outcomes than open repair for non-ruptured abdominal aortic aneurysm. Methods Electronic bibliographic sources (MEDLINE, EMBASE, and CENTRAL) were searched up to July 2019 using a combination of thesaurus and free text terms to identify randomised controlled trials (RCTs) comparing the outcomes of EVAR and open repair. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Pooled estimates of dichotomous outcomes were calculated using odds ratio (OR) or risk difference (RD) and 95% confidence interval (CI). A time to event data meta-analysis was performed using the inverse variance method and the results were reported as summary hazard ratio (HR) and 95% CI. Results Seven RCTs reporting a total of 2 983 patients were included in quantitative synthesis. Three of the trials reported long term follow up that extended to 15.8 years, 14.2 years, and 12.5 years. Meta-analysis found significantly lower odds of 30 day (OR, 0.36; 95% CI 0.20–0.66) and in hospital mortality with EVAR (RD –0.03; 95% CI –0.04 to −0.02). Meta-analysis of the three trials reporting long term follow up found no significant difference in all cause mortality at any time between EVAR and open repair (HR 1.02; 95% CI 0.93–1.13; p = .62). The hazard of all cause (HR 0.62; 95% CI 0.42–0.91) and aneurysm related death within six months (HR 0.42; 95% CI 0.24–0.75) was significantly lower in patients who underwent EVAR, but with further follow up, the pooled hazard estimate moved in favour of open surgery; in the long term (>8 years) the hazard of aneurysm related mortality was significantly higher after EVAR (HR 5.12; 95% CI 1.59–16.44). The risk of secondary intervention (HR 2.13; 95% CI 1.69–2.68), aneurysm rupture (OR, 5.08; 95% CI 1.11–23.31), and death due to rupture (OR, 3.57; 95% CI 1.87–6.80) was significantly higher after EVAR, but the risk of death due to cancer was not significantly different between EVAR and open repair (OR, 1.03; 95% CI 0.84–1.25). Conclusion Compared with open surgery, EVAR results in a better outcome during the first six months but carries an increased risk of aneurysm related mortality after eight years.

Liu W., Yue X., Tchounwou P.B.

The ongoing outbreak of the novel coronavirus disease (COVID-19) that occurred in China is rapidly spreading globally. China’s bond and strict containment measures have been proved (in practice) to significantly reduce the spread of the epidemic. This was obtained through the use of emergency control measures in the epidemic areas and the integration of resources from multiple systems, including business, community, technology, education, and transportation, across the country. In order to better understand how China has managed to reduce the public health and economic impacts of the COVID-19 epidemic, this editorial systematically reviews the specific measures for infection prevention and control of the disease. The best practices for COVID-19 eradication in China provide evidence-based strategies that could be replicated in other countries.