BACKGROUND: Mendelian randomization (MR) offers a powerful approach to study potential causal associations between exposures and health outcomes by using genetic variants associated with an exposure as instrumental variables. In this systematic review, we aimed to summarize previous MR studies and to evaluate the evidence for causality for a broad range of exposures in relation to coronary artery disease and stroke. METHODS AND RESULTS: MR studies investigating the association of any genetically predicted exposure with coronary artery disease or stroke were identified. Studies were classified into 4 categories built on the significance of the main MR analysis results and its concordance with sensitivity analyses, namely, robust, probable, suggestive, and insufficient. Studies reporting associations that did not perform any sensitivity analysis were classified as nonevaluable. We identified 2725 associations eligible for evaluation, examining 535 distinct exposures. Of them, 141 were classified as robust, 353 as probable, 110 as suggestive, and 926 had insufficient evidence. The most robust associations were observed for anthropometric traits, lipids, and lipoproteins and type 2 diabetes with coronary artery; disease and clinical measurements with coronary artery disease and stroke; and thrombotic factors with stroke. CONCLUSIONS: Despite the large number of studies that have been conducted, only a limited number of associations were supported by robust evidence. Approximately half of the studies reporting associations presented an MR sensitivity analysis along with the main analysis that further supported the causality of associations. Future research should focus on more thorough assessments of sensitivity MR analyses and further assessments of mediation effects or nonlinearity of associations.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of death worldwide. The management of HCC is complex, with surgical treatment providing long-term survival in eligible patients. This study aims to present the experience of aggressive surgical management of HCC in Greece. Methods: This is a retrospective multicentre clinical study with 242 patients. Results: Most patients were male (79%) and had a median age of 71 yrs. According to the most recent BCLC criteria, 172 patients (71.1%) were classified as BCLC 0-A stage, 33 patients (13.6%) were classified as BCLC B, and 37 (15.3%) were classified as BCLC C. A total of 54% of the patients underwent major hepatectomy. Major postoperative morbidity was 15.6%, and the 90-day postoperative mortality rate was 4.5%. The median follow-up was 33.5 months. Three- and five-year overall survival was 65% and 48%, respectively. The median overall survival was 55 months. Significantly, five-year survival was 55% for BCLC A, and 34% and 21% for BCLC B and C, respectively. In univariate analysis, cirrhosis, type of resection (R status), and BCLC stage were associated with overall survival. Multivariate analysis indicated that R1 and R2 resections compared to R0, and BCLC C compared to BCLC 0-A, were independently associated with increased mortality. Conclusions: Aggressive surgical treatment of HCC offers satisfactory long-term survival prospects. A significant percentage (29%) of HCCs that underwent liver resection were of the intermediate and advanced BCLC stage. The management of patients with HCC should be discussed in multidisciplinary tumour board meetings on a case-by-case basis to be more effective.

Background: The underlying biological mechanisms linking blood pressure (BP) and cardiovascular diseases (CVD) are only partly understood. We aimed to identify metabolic signatures associated with systolic and diastolic BP and investigate their subsequent association with risk of CVD. Methods and Results: The study included 201 742 UK Biobank participants with measurements on 249 metabolic biomarkers. A multistep adaptive elastic net penalized regression with 10‐fold cross‐validation was employed to identify metabolic signatures for systolic BP and diastolic BP. External validation was conducted on 848 participants from the EHS (Epirus Health Study). We further assessed the associations between BP metabolic signatures and incident composite CVD (N=6742), myocardial infarction (N=4192), and stroke (N=2757) in the UK Biobank, using multivariable Cox regression models. The metabolic signatures comprised 31 and 25 metabolites, robustly correlated with systolic BP and diastolic BP, respectively, in both the UK Biobank and the EHS. Following adjustments (including BP), the metabolic signature for systolic BP was positively associated with incident myocardial infarction (hazard ratio [HR], 1.11 [95% CI, 1.07–1.15]) and CVD (HR, 1.07 [95% CI, 1.04–1.10]). Similarly, the metabolic signature for diastolic BP was associated with a higher risk of myocardial infarction (HR, 1.16 [95% CI, 1.12–1.20]) and CVD (HR, 1.09 [95% CI, 1.05–1.12]). The associations between the signatures and stroke were not significant. The metabolic signatures partly mediated the total effect of the BP traits on the risk of myocardial infarction and CVD. Conclusions: Our findings may enhance our understanding of the biological mechanisms through which BP affects CVD.

Background: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. Materials/Methods: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). Results: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. Conclusions: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials.

Introduction—Aim: Adopting a lifestyle that incorporates regular physical activity confers substantial benefits to both physical and mental health and is recommended for prediabetic individuals. The aim of this study is to investigate the impact of activity tracking apps on increasing physical activity and its effect on glycemic control in people with prediabetes. Materials and Methods: This pilot study included 37 participants, 18 in the prediabetic group and 19 in the normoglycemic group matched for age and gender (mean age 53 years, 40% males). Participants used the Google Fit app for 3 months. The number of daily steps was recorded via the app, and blood and urine tests as well as body fat measurements were conducted before and following 3 months of app use. The co-primary outcome was the change in steps, and the change in HbA1c in both groups. Secondary outcomes were the change in fasting plasma glucose (FPG) (main secondary outcome), as well as lipid parameters, body mass index, visceral fat, and kidney function indices among the two groups. Results: Both groups increased the daily step count following the app intervention, without any statistically significant difference when we compared the steps change between the two groups. We found a statistically significant difference between HbA1c levels in favor of the prediabetic compared to the normoglycemic group [mean difference (MD) 0.16, 95%CI 0.04, 0.28, p-value 0.01)], following the 3-month intervention. Additionally, there was a statistically significant difference between FPG levels in favor of the prediabetic compared to the normoglycemic group (MD 9.06, 95%CI 4.16, 13.96, p-value 0.001). Conclusions: The present study suggests that the use of activity tracking apps, combined with tailored activity goals and monthly supportive phone calls, may contribute to improved glycemic control among individuals with prediabetes.

Background: People with schizophrenia are one of the most stigmatized social groups. The purpose of this study was to assess stigma, quality of life, social anxiety and illness insight in a sample of first-episode psychosis (FEP) patients and to investigate possible correlations between these variables and psychopathology/socio-demographic factors of the study group. Methods: This observational cross-sectional study included 90 patients (55 males, 35 females) with a mean age of 31.8 ± 8.6 years (18–52) experiencing a first episode of psychosis. The mean ± SD duration of untreated psychosis was 13.4 ± 6.2 weeks. The medications used were risperidone (n = 24; 26.7%), clozapine (n = 34; 37.8%), and olanzapine (n = 32; 35.6%). The tools used for this study were the Internalized Stigma for Mental Illness Scale (ISMI), World Health Organization Quality of Life Assessment-BREF (WHOQoL-BREF), Liebowitz Social Anxiety Scale (LSAS-SR), Schedule for the Assessment of Insight—Expanded version (SAI-E), and Positive and Negative Syndrome Scale (PANSS). Results: The mean ISMI total score was 50.9 ± 7.9 (range: 29–84), with 56.6% of patients scoring greater than 50, indicative of internalized stigma. Mean PANSS total scores improved from 76.1 ± 7.2 at baseline to 44.9 ± 6.3 after six months of follow-up (p < 0.001). Patients demonstrated insight of (mean ± SD) 20.3 ± 4.5, measured by SAI-E, and moderate-to-good quality of life across WHOQOL-BREF domains. The results of this study indicated that the ISMI scale showed statistically significant linear correlations with the LSAS-SR [anxiety (r = 0.399, p < 0.001) and avoidance (r = 0.421, p < 0.001)], with positive correlations and approximately medium associations. In the multivariable analyses, ISMI was inversely associated with all WHOQoL-BREF domains (physical health: −0.72 units 95% CI: −1.09 to −0.35, p < 0.001; mental health:−1.04, 95% CI: −1.45 to −0.63, p < 0.001; social relationships: −0.79, 95% CI: −1.39 to −0.18, p = 0.012; environmental health: −0.70, 95% CI: −1.00 to −0.39, p < 0.001). Multivariable models were adjusted for age, gender, medication, marital status, having children, employment, residence, DUP, SAI-E, ISMI, and LSAS-SR. Conclusions: Stigma is positively correlated with social anxiety. Higher stigma levels were independently linearly associated with lower levels of quality of life, even after adjusting for other predictor variables. Our results also indicated an association between higher insight levels and elevated odds of high internalized stigma. Stigma in first-episode psychosis patients is negatively associated with quality of life and positively associated with social anxiety/avoidance.