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Background & Aims: This study used the Global Burden of Disease data (2010-2021) to analyze the rates and trends of point prevalence, annual incidence, and years lived with disability (YLDs) for metabolic dysfunction-associated steatotic liver disease (MASLD) in 204 countries., Methods: Total numbers and age-standardized rates per 100,000 population for MASLD prevalence, annual incidence, and YLDs were compared across regions and countries by age, sex, and sociodemographic index (SDI). Smoothing spline models were used to evaluate the relationship between the burden of MASLD and SDI. Estimates were reported with uncertainty intervals (UI)., Results: Globally, in 2021, the age-standardized rates per 100,000 population of point prevalence of MASLD were 15,018.1 cases (95% UI 13,756.5-16,361.4), annual incidence rates were 608.5 cases (598.8-617.7), and YLDs were 0.5 (0.3-0.8) years. MASLD point prevalence was higher in men than women (15,731.4 vs. 14,310.6 cases per 100,000 population). Prevalence peaked at ages 45-49 for men and 50-54 for women. Kuwait (32,312.2 cases per 100,000 people; 95% UI: 29,947.1-34,839.0), Egypt (31,668.8 cases per 100,000 people; 95% UI: 29,272.5-34,224.7), and Qatar (31,327.5 cases per 100,000 people; 95% UI: 29,078.5-33,790.9) had the highest prevalence rates in 2021. The largest increases in age-standardized point prevalence estimates from 2010 to 2021 were in China (16.9%, 95% UI 14.7%-18.9%), Sudan (13.3%, 95% UI 9.8%-16.7%) and India (13.2%, 95% UI 12.0%-14.4%). MASLD incidence varied with SDI, peaking at moderate SDI levels., Conclusions: MASLD is a global health concern, with the highest prevalence reported in Kuwait, Egypt, and Qatar. Raising awareness about risk factors and prevention is essential in every country, especially in China, Sudan and India, where disease incidence and prevalence are rapidly increasing., Impact and Implications: This research provides a comprehensive analysis of the global burden of MASLD, highlighting its rising prevalence and incidence, particularly in countries with varying sociodemographic indices. The findings are significant for both clinicians and policymakers, as they offer critical insights into the regional disparities in MASLD burden, which can inform targeted prevention and intervention strategies. However, the study's reliance on modeling and available data suggests cautious interpretation, and further research is needed to validate these findings in clinical and real-world settings., Competing Interests: CDB has received grant support from Echosens. YY is a consultant to Zydus and Novo Nordisk. WK reports grants from Glaxo-SmithKline, Gilead, Novartis, Pfizer, Roche, Springbank, Ildong, Galmed, Dicerna, Enyo, Hanmi, Novo Nordisk, and KOBIOLABS; consulting fees from Boehringer Ingelheim, Novo Nordisk, Standigm, Daewoong, TSD Life Sciences Ildong, Olix Pharma, HK Inoen, and KOBIOLABS; honoraria for lectures from Ildong, Samil, and Novo Nordisk, and owns stocks in KOBIOLABS and Lepidyne and he is the founder of Remedygen. GS reports honoraria from Merck, Gilead, AbbVie, Novonordisk, and Pfizer, and unrestricted research funding from Theratecnologies Inc. VW-SW reports grants from Gilead Sciences; consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, TARGET PharmaSolutions; honoraria for lectures from Abbott, AbbVie, Gilead Sciences, Novo Nordisk and he is Chairman of Subspecialty Board of Gastroenterology and Hepatology, Hong Kong College of Physicians and Co-founder of Illuminatio Medical Technology Limited. JB reported receiving grants and personal fees from Echosens. W-KC is a consultant or advisory board member for Abbott, Roche, AbbVie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. JDR received consultancy fees from Falk, Gilead, Pfizer and a speaker honorarium from Takeda. LV reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, and Viatris; honoraria from MSD, Gilead, AlfaSigma, AbbVie, and Resalis, and grants from Gilead. JMS serves as a consultant for Akero, Alentis Therapeutics, Astra Zeneca, Apollo Endosurgery, Boehringer Ingelheim, GSK, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, and Siemens Healthineers. He has received research funding from Gilead Sciences, Boehringer Ingelheim, and Siemens Healthcare GmbH. He holds stock options in AGED diagnostics and Hepta Bio. He has also received speaker honorarium from Gilead Sciences, Advanz, Echosens, MedPublico GmbH. MR-G reported receiving personal fees from Echosens. SUK reported personal fees from Gilead Sciences, GSK, Bayer, Eisai, AbbVie, Echosens, MSD, Bristol-Myers Squibb, AstraZeneca, and grants from AbbVie, Bristol-Myers Squibb, and Gilead Sciences. PNN reported receiving grants from Novo Nordisk, advisory board and personal consulting fees, honoraria for lectures and travel expenses from Novo Nordisk, personal consulting and advisory board fees from Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol-Myers Squibb, Pfizer, MSD, Sun Pharma, Eli Lilly, Madrigal, GSK, and nonfinancial support for educational events from AiCME. AS reported receiving grants from Intercept, Merck, personal consulting fees from Gilead, Pfizer, Genentech, ALnylam, Regeneron, Zydus, LG chem, Hanmi, Madrigal, Path AI, and 89 Bio, grants and personal consulting fees from Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Novartis, and Histoindex, and stock options from Genfit, Tiziana, Durect, Inversago, and Galmed. LAA reports consulting fees from Novo Nordisk, Pfizer, Gilead, and CSL Behring. HH reported personal fees from AstraZeneca, Bristol-Myers Squibb, MSD, Novo Nordisk, Boehringer Ingelheim, KOWA, and GW Phara outside the submitted work, and grants from AstraZeneca, Echosens, Gilead Sciences, Intercept, MSD, Novo Nordisk, and Pfizer outside the submitted work. JG serves on Advisory Boards and receives honoraria for talks from Novo Nordisk, Astra Zeneca, Roche, BMS, Pfizer, Cincera, Pharmaxis, Gilead, AbbVie, and Boehringer Ingelheim. M-HZ has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk, and consulting fees from Boehringer Ingelheim. No other disclosures were reported. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)

Paraneoplastic hypoglycemia, also known as non-islet cell tumor hypoglycemia (NICTH), is a rare but critical condition occurring in patients with different types of malignancy. This condition is commonly linked to tumors producing insulin-like growth (IGF) factors, particularly IGF-2 and its precursors, which disrupt glucose homeostasis and lead to excessive glucose consumption. The diagnosis typically involves documenting symptomatic hypoglycemia and ruling out other potential causes. Essential diagnostic tools include imaging studies and laboratory tests, specifically measuring IGF-2 levels and the IGF-2:IGF-1 ratio. Treatment strategies for NICTH are multifaceted and may include surgical resection of the tumor if feasible, pharmacological interventions such as corticosteroids to suppress IGF-2 production, or supportive measures to manage acute hypoglycemic episodes. Novel therapeutic approaches targeting IGF-2, such as monoclonal antibodies or siRNA, are also being explored and hold promise for future treatment options. This review aims to enhance understanding of paraneoplastic hypoglycemia, focusing on its pathogenesis and diagnosis, to guide optimal medical treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Bisalbuminemia is a rare, typically benign condition marked by the presence of a bifid albumin band on serum protein electrophoresis. It can either be inherited due to a point mutation or acquired in association with various medical conditions, most commonly diabetes mellitus. Bisalbuminuria, the presence of bifid albumin in urine, may or may not accompany bisalbuminemia. Both conditions are often discovered incidentally during screening for monoclonal gammopathy. Bisalbuminemia and related variants provide insights into albumin's genetic diversity and functional roles, influencing clinical diagnostics and research in human genetics. Understanding these variants aids in distinguishing benign conditions from potential disease states, guiding appropriate clinical management. In this case-based review, we present a case of hereditary bisalbuminemia identified unexpectedly during an investigation of a positive Direct Antiglobulin Test Coombs in an adult female patient. This review aims to highlight the key features of bisalbuminemia, a rare condition that should be recognized by clinicians., Competing Interests: The authors declare no conflict of interest., (© 2024 Published by Elsevier Inc.)

Objective: The purpose of this study was to examine sex-related differences in the long-term (20-year) incidence of cardiovascular disease (CVD) and its determinants., Methods: In 2002, 3,042 apparently healthy Greek adults were recruited, and in 2022, the 20-year follow-up was conducted with 2,169 participants, 1,988 of whom had completed CVD assessments. Sex-specific analyses using nested Cox proportional hazards were performed, as well as classification and regression tree (CRT) analysis modeling., Results: Overall, men exhibited higher CVD incidence rates during the 20-year period compared to women; age-adjusted analyses revealed, however, that women displayed higher CVD rates between 55 and 75 years old. CVD mortality and premature mortality were more pronounced in men. Although, CVD presentation in women lagged men, over survival was comparable. Moreover, the CVD risk factors burden was greater in women beyond the age of 35. Clinical risk factors and adherence to the Mediterranean dietary pattern emerged as the most significant predictors of sex-specific 20-year CVD incidence., Conclusion: This study highlights various sex disparities in CVD, challenging prevailing perceptions that CVD is a men's phenomenon. Tailoring prevention strategies to address sex-specific differences, particularly through lifestyle interventions, could effectively reduce CVD burden., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Obesity is a major public health problem with a prevalence increasing at an alarming rate worldwide. There is an urgent need for efficient approaches to weight management. Diet induced thermogenesis (DIT) is the process by which the body increases its energy expenditure in response to a meal. It is estimated to account for approximately 10 % of total energy expenditure and is considered a potentially modifiable component of energy expenditure. The palatability of food, meal's composition in macronutrients, the circadian rhythm and sleep, as well as individual's characteristics such as age, the presence of obesity or diabetes mellitus, and the proportion of physical activity are the main factors that affect DIT. However, studies examining DIT are mostly characterized by small sample size and the methodology varies considerably between studies. It seems that even today there is a lot of contradiction between the relative studies. Inspite of that, future research might lead to the modification of DIT in order to achieve some weight loss in obese people., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: The aim of this study was to present the burden of cardiovascular disease (CVD) and its related risk factors based on a 20-year observation period (2002-2022)., Methods: In 2002, 3042 Greek adults (aged: 45 (12) years) free of CVD, cancer, or any other chronic infections were enrolled. In 2022, the 20-year follow-up was performed on 2169 participants (1988 had complete data for CVD). Lifetime risk for CVDs and disability-adjusted-life-years (DALYs) lost were also calculated., Results: The 20-year CVD incidence was 3600 cases/10,000 individuals (man-to-woman ratio 5:4). At the index age of 40 years, the lifetime risk for developing CVD was 68% for men and 63% for women; as the participants were getting older, the lifetime risk declined by approximately 19% and 13% for men and women, respectively, but remained at high levels, reaching 55% for both sexes. Participants between 45 and 55 years exhibited the highest CVD burden concerning aggregated DALYs. The burden was greater in men than in women, at ages below 35 years; beyond this age threshold, this trend shifted, and women exhibited a higher CVD burden., Conclusion: The burden of CVD in Greece has shown increasing trends over the past 20 years as a result of the accumulative growth of the prevalence of modifiable CVD risk factors. The disability-adjusted life-years lost are the most observed ever before, urging for efficient public health strategies and measures., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

The Coronavirus disease 2019 (COVID-19) pandemic increased the burden of critically ill patients who required hospitalization in the intensive care unit (ICU). Bacterial and fungal co-infections, including bloodstream infections (BSIs), increased significantly in ICU patients with COVID-19; this had a significant negative impact on patient outcomes. Reported data pertaining to BSI episodes from the ICU setting during the COVID-19 pandemic were collected and analyzed for this narrative review. We searched the PubMed database for articles published between March 2020 and October 2023; the terms "COVID-19" AND "bloodstream infections" AND "ICU" were used for the search. A total of 778 articles were retrieved; however, only 27 were exclusively related to BSIs in ICU patients with COVID-19. Data pertaining to the epidemiological characteristics, risk factors, characteristics of bacterial and fungal BSIs, patterns of antimicrobial resistance, and comparisons between ICU and non-ICU patients during and before the COVID-19 pandemic were obtained. Data on antimicrobial stewardship and infection-control policies were also included. The rates of BSI were found to have increased among ICU patients with COVID-19 than in non-COVID-19 patients and those admitted during the pre-pandemic period. Male gender, 60-70 years of age, increased body mass index, high Sequential Organ Failure Assessment scores at admission, prolonged hospital and ICU stay, use of central lines, invasive ventilation, and receipt of extracorporeal membrane oxygenation were all defined as risk factors for BSI. The use of immune modulators for COVID-19 appeared to increase the risk of BSI; however, the available data are conflicting. Overall, Enterococci, Acinetobacter baumannii , and Candida spp. emerged as prominent infecting organisms during the pandemic; along with Enterobacterales and Pseudomonas aeruginosa they had a significant impact on mortality. Multidrug-resistant organisms prevailed in the ICU, especially if antimicrobial resistance was established before the COVID-19 pandemic and were significantly associated with increased mortality rates. The unnecessary and widespread use of antibiotics further increased the prevalence of multidrug-resistant organisms during COVID-19. Notably, the data indicated a significant increase in contaminants in blood cultures; this highlighted the decline in compliance with infection-control measures, especially during the initial waves of the pandemic. The implementation of infection-control policies along with antibiotic stewardship succeeded in significantly reducing the rates of blood contamination and BSI pathogens. BSIs considerably worsened outcomes in patients with COVID-19 who were admitted to ICUs. Further studies are needed to evaluate adequate preventive and control measures that may increase preparedness for the future., (© 2024 The Author(s).)

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Purpose: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece., Methods: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample., Results: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%)., Conclusion: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation., Methods: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal., Results: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156-262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (<20,000 IU/ml) in 150 (20%) and high (>20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels <20,000 IU/ml vs . 60% among patients with pretreatment HBV DNA levels >20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs . 5% ( p <0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p <0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p <0.001)., Conclusions: Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations., Impact and Implications: A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring., Competing Interests: MJS has received speaker’s fees and research support from Roche, Gilead, BMS, and Fujirebio. SMC has nothing to disclose. JYP is an investigator in clinical trials sponsored by AbbVie, Gilead Sciences, Hanmi, and Norvatis. WKS has received speaker’s fees from Mylan and AstraZeneca; has provided consultancy for Abbott; has received speaker’s fees and provided consultancy for AbbVie; and has received speaker’s fees from, provided consultancy for, and received research funding from Gilead Sciences. YT reports lecture fees from Fujirebio, GlaxoSmithKline Pharmaceuticals Ltd, and Gilead Sciences, and research fees from Fujifilm Corp, Janssen Pharmaceutical K.K., Gilead Sciences, GlaxoSmithKline Pharmaceuticals Ltd, Sysmex, and Stanford Junior University. FvB has received research support from and provided consultancy for Roche. TB currently acts as an advisor to AbbVie, Alexion, Bayer, BMS, Gilead, Intercept, Janssen, MSD/Merck, Merz, Novartis, and Sequana Medical. He has received speaking honoraria from AbbVie, Alexion, Bayer, BMS, Eisai, Gilead, Intercept, Ipsen, Janssen, MSD/Merck, Merz, Novartis, Sirtex, and Sequana Medical in the past 2 years. He has received grant support from AbbVie, BMS, Gilead, Humedics, Intercept, Janssen, MSD/Merck, Merz, Novartis, and Sequana Medical. FZ is an advisor for Aicuris, Aligos, Antios, Assembly, Blue Jay, Evotec, Gilead, and GSK, and has received research grants from Assembly, Beam, Janssen, and Viravaxx. SHA has acted as an advisor and investigator for Gilead, Janssen, AbbVie, Roche, Assembly Biosciences, Arbutus, Brii, Vaccitech, GSK, Inovio, Aligos, Vir Biotechnology, SL Vaxigen, GeneOne Life Science, GreenCross, Yuhan, Samil, and Ildong. GND is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, and Sobi; has received research grants from AbbVie and Gilead; and has served as PI in studies for AbbVie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc, Sobi, and Intercept Pharmaceuticals. MB has received fees for consultancy/speakers bureau from AbbVie, Gilead, Janssen, EISAI-MSD, and Roche. HW has received research grants from Abbott, AbbVie, BMS, Gilead, Merck, Novartis, Roche, Roche Diagnostics, and Siemens; consultant fees from Abbott, AbbVie, BMS, Boehringer Ingelheim, Gilead, JJ/Janssen-Cilag, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, and ViiV; and speaker fees from Abbott, AbbVie, BMS, Boehringer Ingelheim, Gilead, JJ/Janssen-Cilag, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, and ViiV. MC has received personal fees from AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck (MSD), Biogen, Falk Foundation, Boehringer Ingelheim, Siemens, and Spring Bank as well as grants and personal fees from Roche. MFY has provided consultancy for and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myers Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, and Spring Bank Pharmaceuticals, and has received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation, and Sysmex Corporation. KA has received fees for consultancy/speakers bureau from Assembly, Aligos, Arbutus, Gilead, Immunocore, Janssen, Roche, Sobi, Spring Bank, and Vir, and research support from Abbott, Gilead, and MSD. AB has received research fees from Fujirebio, Gilead Sciences, and Janssen Pharma. MB reports consultancy and lecture honoraria from AbbVie, Arbutus, Gilead, Janssen, Merck/MSD, and Spring Bank. GP has served as an advisor/lecturer for AbbVie, Albireo, Dicerna, Gilead, GSK, Janssen, Ipsen, MSD, Novo Nordisk, Roche, and Takeda, and has received research grants from AbbVie and Gilead. CHC has nothing to disclose. BM has received speaker and/or consulting fees from Abbott Molecular, Astellas, Intercept, Falk, AbbVie, Norgine, Bristol Myers Squibb, Fujirebio, Janssen-Cilag, Merck (MSD), and Roche. He has also received research support from Abbott Molecular, Altona Diagnostics, Fujirebio, and Roche. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy., Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications., Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion., Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated., Impact and Implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion., Competing Interests: ZB, NM-S, FGR, AM, and CAP declare no potential conflicts of interest that pertain to this work. FT’s laboratory received research grants from Gilead, Allergan, Bristol-Myers Squibb and Inventiva. MB, MP, MI, YJW, FGN, RT, CNF, AEM, KP, TT, and SPS declared no potential conflicts of interest concerning the publication of this article. AM received grant funding from Gilead (clinical trials), Inventiva, Intercept, and Novo-Nordisk; and was a member of the advisory board (Gilead). SKS received research funding from Novartis, Durect, Fibronostics, and Gilead. LR, HM, EC, GBLS, LY, S, YY, EV, and AK declared no potential conflicts of interest concerning the publication of this article. FW received grant support from Grifols. RJ is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Discovery, a spin-off company from University College London, Hepyx Limited, and Cyberliver. He has research collaborations with Yaqrit Discovery, has received speaker fees from Grifols, and is a consultant for Ambys, Takeda, and Bioconvergent Health. AOB declared no potential conflicts of interest concerning the publication of this article. MB declared the following potential conflicts of interest with respect to the publication of this article: personal fees from CLS Behring GmbH (consultant, speaker), Grifols SA (consultant, speaker), Takeda (consultant, speaker), PPTA (speaker), and Octapharma (speaker). XQ declared no potential conflicts of interest concerning the publication of this article. He received a governmental grant from the Young and Middle-aged Scientific and Technological Innovation Talents Support Plan Project of Shenyang (RC210011), which does not influence the publication of this article, for holding the final advisory meeting of the position statement. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background: Greece was recently reclassified from low- to medium-risk country in terms of cardiovascular disease, with 27% of cardiovascular deaths attributed to hypercholesterolemia. EMENO nationwide survey (2013-2016) assessed the epidemiology of dyslipidemia in the general population in Greece., Methods: A random sample of adults was drawn by multistage stratified random sampling based on 2011 census. Standardized questionnaires and blood tests for total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and triglycerides were used. Hypercholesterolemia was defined as TC ≥ 240/200 mg/dL and/or the use of lipid-lowering drugs, hyper-LDL-cholesterolemia as LDL-C ≥160/130/100 mg/dL and/or the use of drugs, hypo-HDL-cholesterolemia as HDL-C <40 mg/dL, and hypertriglyceridemia as triglycerides ≥150 mg/dL. Weighted analysis was applied to adjust for study design, age/sex distribution discrepancies between sample and population and nonresponse., Results: Of 6,006 individuals recruited, 4,298 were analyzed (mean [SD] age 49.2 [18.5] years, men 48.5%, BMI 28.2 [5.7] kg/m 2 ). Mean TC, LDL-C, HDL-C, and TG were 193.9 [44.4], 118.5 [37.6], 49.1 [14.9], and 130.8 [94.4] mg/dL, respectively. The prevalence of hypercholesterolemia was 27.6/52.4% for thresholds ≥240/200 mg/dL, and of hyper-LDL-cholesterolemia was 26.3/46.7/74% for thresholds ≥160/130/100 mg/dL, with no differences between sexes. The prevalence of hypo-HDL-cholesterolemia was 27.5% (men/women 38.1/17.5%, p < 0.001) and of hypertriglyceridemia was 27.8% (men/women 32.6/23.4%, p < 0.001). Lipid-lowering drugs were used by 14.1% of the participants (men/women 12.6/15.6%, p < 0.001)., Conclusions: More than 50% of adults in Greece have some type of dyslipidemia (mainly TC ≥ 200 mg/dL) and 14% are treated. Nationwide programmes are needed to manage dyslipidemia and halt the increasing rate of cardiovascular disease in Greece., Competing Interests: Declaration of competing interest GSS reports advisory and lecture fees from Astra-Zeneca, Menarini, Novartis, Sanofi-Aventis, Servier. CV reports research grants and honoraria from Amgen, Vianex, Elpen, Pfizer, Lilly, Menarini, Servier, Sanofi, Viatris, Winmedica. ENL reports personal fees paid to his institution from Amgen, Novartis, Sanofi, Novo Nordisk, Lilly and Servier, outside the submitted work. LR reports research grants and honoraria from Amgen, Elpen, Sanofi-Aventis, Mylan, Novartis, and Servier. DR reports personal fees for lectures and AB from Amgen, Novartis, Sanofi, Novo Nordisk, Lilly and Servier, Menarini, Viatris, Recordati, Boehringer, Elpen, Bayer, Roche, Medtronic, Edwards, Astra-Zeneca, Demo, outside the submitted work. MG received honoraria paid through her institution from Merck, for advisory boards and lectures unrelated to this study. GT has received EU and National resources grants as well as a grant from the Hellenic Diabetes Association, all paid to her institution, to support this study and grants unrelated to this study and paid to her institution from Gilead Sciences Europe, UCL, ECDC, EU, and National funds. The other authors report no relationships that could be construed as a conflict of interest., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Objective: Acute myocardial infarction (AMI) is one of the leading causes of death; however, updated data regarding clinical presentation and current management are missing in Greece. This study aimed to prospectively record the demographic and clinical characteristics of a representative sample of patients suffering from AMI, their management, and short-term outcomes., Methods: ILIAKTIS is a national, prospective, multicenter, noninterventional study conducted under the auspices of Hellenic Society of Cardiology (HCS) and the European Initiative Stent - Save a Life. From 1 st April 2020 to 30 th June 2020, consecutive adult patients with STEMI or NSTEMI were enrolled in the 50 participating hospitals, appropriately selected to match the geographical and population distribution in the Greek territory., Results: In total, 1862 patients (mean age: 64.2 ± 13.2 yrs.; 77.2% males) with AMI were enrolled. More patients presented with NSTEMI (56.8%) than with STEMI (43.2%). Primary PCI (pPCI) was the preferable treatment option for STEMI patients in PCI-hospitals (76.9% vs. 39.9% for non-PCI, p < .001) and thrombolysis in non-PCI-hospitals (47.3% vs. 17.9% for PCI-hospitals, p < .001). The mean length of hospital stay was 5.6 days. In-hospital mortality was less likely in NSTEMI compared to that in STEMI patients (aOR = 0.30; 95% CI 0.18 to 0.49). Patients initially admitted in non-PCI-hospitals showed increased risk for in-hospital (aOR = 2.29; 95% CI 1.20 to 4.42) and 30-day mortality (aOR = 1.88; 95% CI 1.20 to 2.96)., Conclusion: This study shows that the proportion of STEMI and NSTEMI patients managed interventionally has significantly increased, resulting in better clinical outcomes compared to previous Greek surveys., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

The ever-increasing burden of obesity demands a better pathophysiological understanding, especially regarding adipose tissue pathophysiology. Animal models of obesity are of great importance in investigating potential mechanisms and implications of obesity. Many issues should be considered while interpreting the preclinical results as anatomical and pathophysiological differences exist among species. Importantly, the natural history of obesity development differs considerably. An important example of conflicting results among preclinical models and human physiological studies is that of adipose tissue oxygenation, where rodent models almost unanimously have shown the presence of hypoxia in the adipose tissue of obese animals while human studies have yielded conflicting results to date. Other issues which require further clarification before generalizing preclinical data in humans include adipose tissue browning, endocrine function and fibrosis. The aim of this mini-review is to synopsize similarities and differences between rodent models and humans, which should be taken into consideration in obesity studies., (© 2022 The Authors.)

Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions against the global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates of protection against severe disease and mortality. Barely a year after vaccines became available, the Omicron variant and its unprecedented speed of transmission has posed a new challenge. Overall, Omicron presents increased immune escape, transmissibility, and decreased pathogenicity. Vaccines do not offer a full protection against SARS-CoV-2 acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who may in turn spread the virus to others. Breakthrough infections may be causally related to the viral profile (viral variant and load, incubation period, transmissibility, pathogenicity, immune evasion), immunity characteristics (mucosal versus systemic immunity, duration of immunity, etc.), host determinants (age, comorbidities, immune status, immunosuppressive drugs) and vaccination properties (platform, antigen dose, dose number, dose interval, route of administration). Determining the rate of breakthrough infections may be challenging and necessitates the conduction of population-based studies regarding vaccine effectiveness as well as neutralizing antibody testing, a surrogate of immune protection. In this review, we analyze the causes of breakthrough infections, their clinical consequences (severity of infection and transmission), methods of determining their incidence as well as challenges and perspectives. Long COVID as well as multi-inflammatory syndrome in adolescents may be significantly reduced in breakthrough infections. The need for universal pancoranavirus vaccines that would aim at protecting against a plethora of SARS-CoV-2 variants as well as emerging variants is discussed. Finally, novel vaccine strategies, such as nasal vaccines, may confer robust mucosal and systemic protection, reducing efficiently transmission., Competing Interests: No conflict of interest to disclose., (© 2022 The Authors.)

Reactivation of varicella-zoster virus (VZV) has been reported after the administration of different vaccine platforms against SARS-CoV-2, also among individuals without known immunosuppressive states. Herein, we describe for the first time a case of herpes zoster after mRNA vaccination against SARS-CoV-2 in a 53-year-old immunocompetent adult without any known comorbidities, who was previously vaccinated with a live attenuated zoster vaccine. The fact that the patient had no history of varicella and had been tested seronegative for VZV prior to immunization with the live attenuated zoster vaccine further contribute to the challenge of this unusual case. This advocates for a high level of vigilance on the part of clinicians regarding this rare complication among receivers of COVID-19 vaccines., Competing Interests: None declared., (© 2022 Published by Elsevier Inc.)

The recognition of the rare but serious and potentially lethal complication of vaccine induced thrombotic thrombocytopenia (VITT) raised concerns regarding the safety of COVID-19 vaccines and led to the reconsideration of vaccination strategies in many countries. Following the description of VITT among recipients of adenoviral vector ChAdOx1 vaccine, a review of similar cases after Ad26.COV2·S vaccination gave rise to the question whether this entity may constitute a potential class effect of all adenoviral vector vaccines. Most cases are females, typically younger than 60 years who present shortly (range: 5-30 days) following vaccination with thrombocytopenia and thrombotic manifestations, occasionally in multiple sites. Following initial incertitude, concrete recommendations to guide the diagnosis (clinical suspicion, initial laboratory screening, PF4-polyanion-antibody ELISA) and management of VITT (non-heparin anticoagulants, corticosteroids, intravenous immunoglobulin) have been issued. The mechanisms behind this rare syndrome are currently a subject of active research and include the following: 1) production of PF4-polyanion autoantibodies; 2) adenoviral vector entry in megacaryocytes and subsequent expression of spike protein on platelet surface; 3) direct platelet and endothelial cell binding and activation by the adenoviral vector; 4) activation of endothelial and inflammatory cells by the PF4-polyanion autoantibodies; 5) the presence of an inflammatory co-signal; and 6) the abundance of circulating soluble spike protein variants following vaccination. Apart from the analysis of potential underlying mechanisms, this review aims to synopsize the clinical and epidemiologic features of VITT, to present the current evidence-based recommendations on diagnostic and therapeutic work-up of VITT and to discuss new dilemmas and perspectives that emerged after the description of this entity., Competing Interests: No conflict of interest to disclose, (© 2021 Published by Elsevier Inc.)

Remdesivir (GS-5734), a drug initially developed to treat hepatitis C and Ebola virus disease, was the first approved treatment for severe coronavirus disease 2019 (COVID-19). However, apart from remdesivir, there is a paucity of other specific anti-viral agents against SARS-CoV-2 infection. In 2017, researchers had documented the anti-coronavirus potential of remdesivir in animal models. At the same time, trials performed during two Ebola outbreaks in Africa showed that the drug was safe. Although vaccines against SARS-CoV-2 infection have emerged at an enormously high speed, equivalent results from efforts towards the development of anti-viral drugs, which could have played a truly life-saving role in the current stage of the pandemic, have been stagnating. In this review, we will focus on the current treatment options for COVID-19 which mainly consist of repurposed agents or treatments conferring passive immunity (convalescent plasma or monoclonal antibodies). Additionally, potential specific anti-viral therapies under development will be reviewed, such as the decoy miniprotein CTC-445.2d, protease inhibitors, mainly against the Main protein Mpro, nucleoside analogs, such as molnupiravir and compounds blocking the replication transcription complex proteins, such as zotatifin and plitidepsin. These anti-viral agents seem to be very promising but still require meticulous clinical trial testing in order to establish their efficacy and safety. The continuous emergence of viral variants may pose a real challenge to the scientific community towards that end. In this context, the advent of nanobodies together with the potential administration of a combination of anti-viral drugs could serve as useful tools in the armamentarium against COVID-19., Competing Interests: No conflict of interest to disclose., (© 2021 Published by Elsevier Inc.)

Introduction: This case report describes a fetus with compound heterozygosity for Hb G-Hsi-Tsou and beta thalassemia, diagnosed in a healthy pregnancy. To the best of our knowledge, this is the first documented case of compound heterozygosity and the woman is the second known case of heterozygosity for Hb G-Hsi-Tsou., Case Presentation: A 34-year-old woman during her first pregnancy underwent hemoglobin electrophoresis which revealed heterozygosity for Hb G-Hsi-Tsou. Hemoglobin G-Hsi-Tsou constitutes a hemoglobin variant with a structural abnormality of the beta chain, first described in 1972, but since then no other cases have been reported. After finding out that her husband was heterozygous for beta thalassemia, chorionic villus sampling revealed the embryo's heterozygosity for both Hb G-Hsi-Tsou and beta thalassemia. Due to lack of scientific data, the couple decided to end the pregnancy., Conclusion: It was not possible to determine whether the fetus would present serious deficiencies in hematopoiesis, as Hb G-Hsi-Tsou is a variant which is not yet fully understood. What made this case even more complex was the simultaneous presence of the beta thalassemia allele., (© 2020 The Authors.)

Background: Diabetes mellitus (DM) is the most common metabolic disorder that increases the risk of cardiovascular disease by two to four times compared with the general population. There are limited data on the prevalence of heart diseases in subjects with DM in Greece. In this study, we examined the prevalence of self-reported DM as well as cardiac and other main comorbidities in a representative sample of the adult Greek population., Methods: The target study population included 30,843 participants stratified by gender, age, and district, and this was a representative sample of the adult Greek population in 2010. A structured questionnaire was built to report the prevalence of self-reported DM and the main comorbidities in participants with and without DM. Collection of data was performed through telephone interviews., Results: The prevalence of self-reported DM was 6.6%. The prevalence of the main comorbidities in participants with DM vs. those without DM was as follows: heart diseases 24.0% vs. 8.9%, p<0.001; lung diseases 11.3% vs. 5.3%, p<0.001; kidney diseases 3.4% vs. 1.2%, p=0.001; liver diseases 1.4% vs. 0.7%, p=0.001; benign blood diseases 1.6% vs. 0.9%, p=0.005; and solid organ and/or blood malignancies 2.9% vs. 1.5%, p<0.001., Conclusions: The prevalence of self-reported DM in a representative sample of the adult Greek population in 2010 was 6.6%. The prevalence of heart diseases in subjects with DM was 2.7-fold higher than the prevalence in those without DM. Diseases of the lung, kidney, liver, and blood as well as malignancies were significantly more common among participants with DM., (Copyright © 2018 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Economic crisis poses an immense threat to public health worldwide and has been linked to cardiovascular morbidity and mortality. Greece is facing a distinctive recession over the recent years. However, the exact impact on coronary artery disease (CAD) burden has not been adequately addressed., Methods: Demographic, clinical, and angiographic data of 3895 hospitalized patients were retrospectively studied. Patients were classified into two groups: those before crisis (2006-2007, n = 1228) and those during crisis (2011-2015, n = 2667)., Results: All data before and during crisis were compared. During crisis, patients presented with less acute coronary syndrome (ACS - 45.5% vs. 39.9%, p < 0.001). Subsequently, there were more patients without CAD (23.7% vs. 35.1%, p < 0.001) or one-vessel disease (20.5% vs. 23%, p < 0.001). The prevalence of traditional risk factors decreased significantly or remained stable except obesity (26.3% vs. 31.4%, p = 0.002). A significant increase in the examined females (23.6% vs. 26.7%, p = 0.04) was also observed., Conclusions: The burden of CAD in Greece was partially affected during the financial crisis. Even though the incidence of ACS was decreased, more women and more patients with no- or single-vessel disease were referred for cardiac catheterization. In addition, the prevalence of traditional risk factors for CAD did not increase except obesity confirming the "obesity paradox." It seems that the impact of traditional risk factors for CAD is not an immediate process and is somewhat related to living conditions or other exogenous and social factors., (Copyright © 2018 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins., Methods: Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin., Results: Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001)., Conclusions: Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.

Colorectal liver metastases (CRLM) present an important clinical challenge in both surgical and medical oncology. Despite improvements in management, survival among patients undergoing resection of CRLM is still very variable and there is a paucity of clinical trial data and reliable biomarkers that could guide prognostic forecasts, treatment selection, and follow-up. Fortunately, recent advances in molecular biology and tumor sequencing have identified a number of critical genetic loci and proliferation markers that may hold the key to understanding the biologic behavior of CRLM; specifically, mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite instability appear to have a decisive impact on prognosis and response to treatment in patients with CRLM. While the applicability of genetic biomarkers in everyday clinical practice remains conditional on the development of inexpensive bedside sequencing, targeted therapies, and the conduct of appropriate clinical trials, the promise of personalized treatment may be closer to realization than ever before.

Calcium channel blockers (CCBs) have a narrow therapeutic index, and their intake in excess is associated with a critical clinical presentation of sustained hypotension and non-cardiogenic pulmonary edema, which are difficult to treat. Unfortunately, the available treatments fail to resuscitate a significant number of patients poisoned by CCBs, rendering them the main cardiovascular drugs involved in death due to overdose. Importantly, in all cases reported until now in the literature, CCB intoxication was known at the time of patients' presentation and the medical challenge solely consisted of the therapeutic approach. In this case report, we describe our experience in treating a 72-year-old patient with recurrent episodes of sustained hypotension refractory to crystalloid and vasoconstrictor infusions. Prolonged pharmacologic support and intermittent sessions of hemofiltration induced stabilization and recovery. The results of an extensive diagnostic workup to elucidate the cause were unfruitful. The recurrent and paroxysmal nature of the clinical presentation along with its incidence after the patient left the protected setting of the hospital led the diagnostic approach to search for a possible external factor, which was shown to be, after toxicological investigation, unintentional amlodipine intoxication., (Copyright © 2016 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Objective: Chronic intermittent renal replacement therapy(RRT) is an alternate method of decongestion for patients presenting with diuretic-resistant, end-stage heart failure(HF) and cardiorenal syndrome. The optimal method of vascular access has not been confirmed. This study investigated the 6-month outcomes of patients with end-stage HF after the creation of arteriovenous communications (AVC) compared with other means of RRT., Methods: We treated 40 patients with chronic, intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of AVC, and 25 (62.5%; Group B) received intraperitoneal (n=6) or internal jugular catheters (n=19) with the goal of achieving body weight stabilization and relief from congestion., Results: The characteristics of the two groups were similar. According to Cox regression analysis, the 6-month rate of death or re-hospitalization for HF was significantly higher in Group A (73%) than in Group B (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P=0.02. Over a 6-month follow-up, the cumulative survival was significantly shorter (P=0.03) in Group A (13.8±10 weeks) than in Group B (20.7±7 weeks). In the 15 patients who received AVC, the only independent predictor of adverse outcome at 6 months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p=0.02), whereas in the 25 patients who underwent other means of RRT, pulmonary vascular resistance (PVR) was identified as a risk factor for hospitalization or death at 1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p=0.04)., Conclusion: In patients with end-stage HF, the creation of AVC for intermittent RRT was followed by a significant increase in morbidity and mortality in comparison to the safe and effective placement of permanent central venous catheters. Patients with elevated PVR seem to comprise a group at high risk for adverse outcomes after central catheter insertion., (Copyright © 2016 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Arterial hypertension and aortic valve stenosis are common disorders and frequently present as concomitant diseases, especially in elderly patients. The impact of hypertension on heart haemodynamics is substantial, thus affecting the clinical presentation of any coexisting valvulopathy, especially of aortic stenosis. However, the interaction between these 2 entities is not thoroughly discussed in the European or/and American guidelines on the management of hypertension or/and valvular heart disease. The present review summarizes all available evidence on the potential interplay between hypertension and aortic valve stenosis, aiming to help physicians understand the pathophysiology and select the best diagnostic and therapeutic strategies (medical or/and interventional) for better management of these high-risk patients, taking into account the impact on outcome as well as the risk-benefit-ratio., (Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)