Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.

Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [-18.4%(3.1) vs. -22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [-0.68 (0.22) vs. -0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.

Evaluation of the Perceptions, Attitudes and Practices among Greek Non-Professional Athletes Visiting a Public Hospital during March 2022, towards COVID-19 Vaccination and Its Consequences on Sports Training and Sports Activity.

Sports have been majorly impacted by the COVID-19 pandemic. After the lockdown period, vaccination and protocols were implemented to return to normality. We aimed to assess the attitudes and practices related to COVID-19 vaccination among athletes, and to record adverse effects of vaccination, if any. A questionnaire was distributed to 1012 male and female athletes, 15+ years old, within the region of Athens. Vaccination coverage with at least one dose was 93.5%, whereas 53.9% were fully vaccinated. More than half of the participants were infected with SARS-CoV-2 at the time of the study. More than 90% of the participants, considered the vaccines as safe, effective and important for public health. Concern about potential side-effects was raised especially by women athletes (59.1% of women compared to 42.2% of men, p < 0.001). The main reasons for avoiding vaccination were fear of vaccine safety, concern about the short time period for vaccine development and testing and doubt of risk of being exposed to SARS-CoV-2 infection. The main reported side-effects were pain at the injection site, fatigue, fever and headache. Approximately two thirds of the participants reported that vaccination did not affect their training, and none reported missing participation in scheduled athletic events. Participants reported high compliance to preventive measures by themselves and fellow athletes, but low satisfaction regarding the implementation of public protocols and the flow of information provided by the authorities. Athletes of older age and those less concerned about potential side-effects were more likely to get fully vaccinated. Nevertheless, the vast majority of the athletes in our study were vaccinated for COVID-19 despite any hesitation regarding effectiveness, safety, or potential side-effects from the vaccines.

Vaccination Against SARS-CoV-2 Protects from COVID-19-induced Endothelial Dysfunction.

BACKGROUND: Coronavirus Disease-19 (COVID-19) is implicated in endotheliitis, which adversely affects cardiovascular events. The impact of vaccination with COVID-19 on the clinical outcome of patients is documented. OBJECTIVE: To evaluate the impact of vaccination with COVID-19 on the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection-related endothelial impairment. METHODS: We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical and laboratory data were collected, and brachial artery flow-mediated dilation (FMD) was evaluated. Subjects without COVID-19 were used as the control group. RESULTS: There was no difference in age (64.7 ± 7.5 years vs. 61.2 ± 11.1 years vs. 62.4 ± 9.5, p = 0.28), male sex (49% vs. 60% vs. 52%, p = 0.71), control subjects, vaccinated, and unvaccinated subjects with COVID-19, respectively. Of the patients with COVID-19, 44% were vaccinated against SARS-CoV-2. Unvaccinated COVID-19 patients had significantly impaired FMD compared to vaccinated COVID-19 patients and Control subjects (2.05 ± 2.41 % vs. 7.24 ± 2.52% vs. 7.36 ± 2.94 %, p <0.001). Importantly, post hoc tests revealed that unvaccinated COVID-19 patients had significantly impaired FMD from both Vaccinated COVID-19 subjects (p <0.001) and from Control subjects (p <0.001). There was no difference in FMD between the control group and the vaccinated COVID-19 group (p = 0.99). CONCLUSION: Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well compared to vaccinated patients with COVID-19. Vaccinated hospitalized subjects with COVID-19 do not show endothelial dysfunction, strengthening the protective role of vaccination against SARS-CoV-2.

Increased Influenza Vaccination Coverage among Members of the Athens Medical Association Amidst COVID-19 Pandemic.

Healthcare workers are at high risk of influenza virus infection as well as of transmitting the infection to vulnerable patients who may be at high risk of severe illness. The aim of this cross-sectional study was to investigate the prevalence and related factors of influenza vaccination coverage (2020-2021flu season), among members of the Athens Medical Association in Greece. This survey employed secondary analysis data from a questionnaire-based dataset on COVID-19 vaccination coverage and associated factors from surveyed doctors, registered within the largest medical association in Greece. All members were invited to participate in the anonymous online questionnaire-based survey over the period of 25 February to 13 March 2021. Finally, 1993 physicians (60% males; 40% females) participated in the study. Influenza vaccination coverage was estimated at 76%. Logistic regression analysis demonstrated that older age (OR = 1.02; 95% C.I. = 1.01-1.03), history of COVID-19 vaccination (OR = 2.71; 95% C.I. = 2.07-3.56) and perception that vaccines in general are safe (OR = 16.49; 95% C.I. = 4.51-60.25) were found to be independently associated factors with the likelihood of influenza vaccination coverage. Public health authorities should maximize efforts and undertake additional actions in order to increase the percentage of physicians/health care workers (HCWs) being immunized against influenza. The current COVID-19 pandemic offers an opportunity to focus on tailored initiatives and interventions aiming to improve the influenza vaccination coverage of HCWs in a spirit of synergy and cooperation.

Evaluation of Knowledge, Attitudes and Practices Related to Self-Testing Procedure against COVID-19 among Greek Students: A Pilot Study.

The COVID-19 pandemic has had a major impact on health, economy, society and education. In the effort to return to normalcy, according to the instructions of the Greek Government for the resumption of the operation of schools, a screening Rapid Antigen Detection Test with the method of self-testing is required for students twice per week, for the early identification and isolation of positive cases. We aimed to pivotally investigate the knowledge, attitudes and practices related to self-testing procedures against COVID-19 among Greek students. A questionnaire was distributed to a convenient sample of students in the region of Athens. Information about the vaccination coverage against SARS-CoV-2 was also obtained. Our study included 1000 students, with 70% of them having an average grade at school. Most of the participants were aware of coronavirus (98.6%) and the self-test (95.5%). The vast majority of students (97%) performed self-testing twice per week, with the 70% them being assisted by someone else. Nearly one sixth of the participants had been infected by COVID-19 (14%) while 36% of them have already been vaccinated against SARS-CoV-2. In conclusion, we report high compliance with the COVID-19 self-testing procedure among students in Attica, Greece. Older age adolescents are more likely to not comply with the regulations of self-testing. Consequently, tailored interventions targeted at older age adolescents are warranted in order to increase the acceptability of self-testing.

The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity. METHODS: We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWFAg), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported. RESULTS: A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05). CONCLUSION: Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress.

Reported COVID-19 Vaccination Coverage and Associated Factors among Members of Athens Medical Association: Results from a Cross-Sectional Study.

There are limited data on the prevalence and determinants of COVID-19 vaccination coverage among physicians. A cross-sectional, questionnaire-based, online study was conducted among the members of the Athens Medical Association (I.S.A.) over the period 25 February to 13 March 2021. All members of I.S.A. were invited to participate in the anonymous online survey. A structured, anonymous questionnaire was used. Overall, 1993 physicians participated in the survey. The reported vaccination coverage was 85.3%. The main reasons of no vaccination were pending vaccination appointment followed by safety concerns. Participants being informed about the COVID-19 vaccines by social media resulted in lower COVID-19 vaccination coverage than health workers being informed by other sources. Logistic regression analysis demonstrated that no fear over COVID-19 vaccination-related side effects, history of influenza vaccination for flu season 2020-2021, and the perception that the information on COVID-19 vaccination from the national public health authorities is reliable, were independent factors of reported COVID-19 vaccination coverage. Our results demonstrate a considerable improvement of the COVID-19 vaccination uptake among Greek physicians. The finding that participants reported high reliability of the information related to COVID-19 vaccination provided by the Greek public health authorities is an opportunity which should be broadly exploited by policymakers in order to combat vaccination hesitancy, and further improve COVID-19 vaccination uptake and coverage among physicians/HCWs, and the general population.

Medical education challenges and innovations during COVID-19 pandemic.

COVID-19 pandemic has undoubtedly disrupted the well-established, traditional structure of medical education. Τhe new limitations of physical presence have accelerated the development of an online learning environment, comprising both of asynchronous and synchronous distance education, and the introduction of novel ways of student assessment. At the same time, this prolonged crisis had serious implications on the lives of medical students including their psychological well-being and the impact on their academic trajectories. The new reality has, on many occasions, triggered the 'acting up' of medical students as frontline healthcare staff, which has been perceived by many of them as a positive learning and contributing experience, and has led to a variety of responses from the educational institutions. All things considered, the urgency for rapid and novel adaptations to the new circumstances has functioned as a springboard for remarkable innovations in medical education,including the promotion of a more "evidence-based" approach.

The Impact of Peripheral Eosinophil Counts and Eosinophil to Lymphocyte Ratio (ELR) in the Clinical Course of COVID-19 Patients: A Retrospective Study.

BACKGROUND/AIM: Eosinophils are blood cells responsible for response against parasites and allergens. Eosinophil to lymphocyte ratio (ELR) is a biomarker for inflammatory conditions. Our aim was to evaluate the role of eosinophils and ELR in COVID-19 patients. PATIENTS AND METHODS: The study included 96 patients hospitalized with COVID-19. They were classified into moderate to severe cases and critical cases. Eosinophils and ELR were determined in both groups, in patients that died or survived and were correlated to duration of hospitalization. RESULTS: There was a statistically significant decrease in eosinophils and ELR between patients that died and patients that survived (p<0.05), and in mean values of the two biomarkers (p<0.05 for eosinophils and p<0.05 for ELR) between patients hospitalized for more or less than 15 days among those with moderate to severe disease. CONCLUSION: Lower eosinophil counts and ERL could probably predict worse outcome in COVID-19 patients.

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.