Tocilizumab administration for the treatment of hospitalized patients with COVID-19: A systematic review and meta-analysis.

Tocilizumab has been repurposed against the 'cytokine storm' in the setting of coronavirus disease 2019 (COVID-19). Our aim was to evaluate the efficacy of tocilizumab in the management of hospitalized COVID-19 patients. We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalized COVID-19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalization and differences in mortality in subgroups (ICU and non-ICU patients and patients receiving or not receiving concomitant corticosteroids). We included 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio [RR] 0.89, 95% CI 0.82 to 0.96) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while no significant reduction was observed in observational studies. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while that was not the case in the RCTs. Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalized patients with moderate-to-critical COVID-19.

Reduction in Hospitalizations for Respiratory Diseases during the First COVID-19 Wave in Greece.

INTRODUCTION: During the first COVID-19 wave, a considerable decline in hospital admissions was observed worldwide. AIM: This retrospective cohort study aimed to assess if there were any changes in the number of patients hospitalized for respiratory diseases in Greece during the first CO-VID-19 wave. METHODS: In the present study, we evaluated respiratory disease hospitalization rates across 9 tertiary hospitals in Greece during the study period (March-April 2020) and the corresponding period of the 2 previous years (2018-2019) that served as the control periods. Demographic data and discharge diagnosis were documented for every patient. RESULTS: Of the 1,307 patients who were hospitalized during the study period, 444 (35.5%) were males with a mean (±SD) age of 66.1 ± 16.6 years. There was a 47 and 46% reduction in all-cause respiratory morbidity compared to the corresponding periods of 2018 and 2019, respectively. The mean incidence rate for respiratory diseases during the study period was 21.4 admissions per day, and this rate was significantly lower than the rate during the same period in 2018 (40.8 admissions per day; incidence rate ratio [IRR], 0.525; 95% confidence interval [CI], 0.491-0.562; p < 0.001) or the rate during 2019 (39.9 admissions per day; IRR, 0.537; 95% CI, 0.502-0.574; p < 0.001). The greatest reductions (%) in the number of daily admissions in 2020 were observed for sleep apnoea (87% vs. 2018 and 84% vs. 2019) followed by admissions for asthma (76% vs. 2018 and 79% vs. 2019) and chronic obstructive pulmonary disease (60% vs. 2018 and 51% vs. 2019), while the lowest reductions were detected in hospitalizations for pulmonary embolism (6% vs. 2018 and 23% vs. 2019) followed by tuberculosis (25% vs. both 2018 and 2019). DISCUSSION/CONCLUSION: The significant reduction in respiratory admissions in 2020 raises the reasonable question of whether some patients may have avoided seeking medical attention during the COVID-19 pandemic and suggests an urgent need for transformation of healthcare systems during the pandemic to offer appropriate management of respiratory diseases other than COVID-19.

The effectiveness of photodynamic therapy and cryotherapy on patients with basal cell carcinoma: A systematic review and meta-analysis.

Basal cell carcinoma (BCC) is known as the most common type of nonmelanoma skin cancer worldwide. The aim of this study is to show the effectiveness of photodynamic therapy and cryotherapy in patients with BCCs with the use of meta-analyses in order to see if there is a possible superiority of one treatment over the other. We searched the databases PubMed, MEDLINE, CINAHL, Scopus, OVID, Embase, Science Direct, JAMA Dermatology, and Research Gate in April 2020. The search combined related terms for cryotherapy, BCC, cryosurgery, cryoablation, laser and photodynamic therapy. The comparison of photodynamic therapy (PDT) vs cryotherapy on recurrence rate yielded no statistically significant results (Figure 2; N = 3 randomized control trials [RCTs]; Summary Random Effects OR = 4.99; P = .212). We observed large heterogeneity (I2 = 87.3%), but no indication for small study effects (Egger's test, P = .02). Regarding the comparison of PDT vs cryotherapy on complete response, again no statistically significant results were observed (Figure 3; N = 2 RCTs; Summary Fixed Effects OR = 0.83; P = .538) and no indication of heterogeneity (I2 = 0%). Our meta-analyses indicated that the comparison of PDT vs cryotherapy has no statistically significant results. Therefore, these therapies seem to have similar therapeutic effects.

Rare coding variants pinpoint genes that control human hematological traits.

The identification of rare coding or splice site variants remains the most straightforward strategy to link genes with human phenotypes. Here, we analyzed the association between 137,086 rare (minor allele frequency (MAF) <1%) coding or splice site variants and 15 hematological traits in up to 308,572 participants. We found 56 such rare coding or splice site variants at P<5x10-8, including 31 that are associated with a blood-cell phenotype for the first time. All but one of these 31 new independent variants map to loci previously implicated in hematopoiesis by genome-wide association studies (GWAS). This includes a rare splice acceptor variant (rs146597587, MAF = 0.5%) in interleukin 33 (IL33) associated with reduced eosinophil count (P = 2.4x10-23), and lower risk of asthma (P = 2.6x10-7, odds ratio [95% confidence interval] = 0.56 [0.45-0.70]) and allergic rhinitis (P = 4.2x10-4, odds ratio = 0.55 [0.39-0.76]). The single new locus identified in our study is defined by a rare p.Arg172Gly missense variant (rs145535174, MAF = 0.05%) in plasminogen (PLG) associated with increased platelet count (P = 6.8x10-9), and decreased D-dimer concentration (P = 0.018) and platelet reactivity (P<0.03). Finally, our results indicate that searching for rare coding or splice site variants in very large sample sizes can help prioritize causal genes at many GWAS loci associated with complex human diseases and traits.

Improving the Accuracy of Low-Cost Sensor Measurements for Freezer Automation.

In this work, a regression method is implemented on a low-cost digital temperature sensor to improve the sensor's accuracy; thus, following the EN12830 European standard. This standard defines that the maximum acceptable error regarding temperature monitoring devices should not exceed 1 °C for the refrigeration and freezer areas. The purpose of the proposed method is to improve the accuracy of a low-cost digital temperature sensor by correcting its nonlinear response using simple linear regression (SLR). In the experimental part of this study, the proposed method's outcome (in a custom created dataset containing values taken from a refrigerator) is compared against the values taken from a sensor complying with the EN12830 standard. The experimental results confirmed that the proposed method reduced the mean absolute error (MAE) by 82% for the refrigeration area and 69% for the freezer area-resulting in the accuracy improvement of the low-cost digital temperature sensor. Moreover, it managed to achieve a lower generalization error on the test set when compared to three other machine learning algorithms (SVM, B-ELM, and OS-ELM).

Robotic assisted and exoskeleton gait training effect in mental health and fatigue of multiple sclerosis patients. A systematic review and a meta-analysis.

PURPOSE: Robotic and Exoskeleton Assisted Gait Training (REAGT) has become the mainstream gait training module. Studies are investigating the psychosocial effects of REAGT mostly as secondary outcomes. Our systematic review and meta-analysis aims to investigate the effects of REAGT in MS patients' mental health and fatigue. MATERIALS AND METHODS: We searched the electronic databases (Scopus, PubMed, Pedro, Cochrane Trials, Dare) for RCT studies fulfilling our inclusion criteria. A meta-analysis of available assessment tools was conducted calculating the summary mean differences in two different timepoints, before and after the intervention using random-effects models. RESULTS: The systematic search of the electronic databases identified 302 studies. Seven RCT studies were considered eligible for data extraction and meta-analysis, according to our eligibility criteria. We were able to obtain adequate data to proceed with a quantitative synthesis for QoL SF36-MC (Mental Component), QoL SF-36 mental and psychosocial subscales, Multiple Sclerosis Quality of Life-54-Mental Health Composite (MSQoL-54-MHC), Patient's Health Questionnaire (PHQ-9) and Fatigue Severity Scale (FSS). CONCLUSIONS: Overall, REAGT seems to have a positive effect to Quality of Life, especially in MS patients' perspective of General and Mental Health and a slight positive effect in depression as measured by PHQ-9.Implications for rehabilitationMultiple Sclerosis (MS) decreases physical and non-physical aspects of patients' quality of life perspective.Rehabilitation strategy must take into consideration the non-physical effects of a training intervention.Robotic and Exoskeleton Gait Training has a positive effect in MS patients' non-physical quality of life and a slight positive effect in depression.

Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

Deep Learning for Lung Cancer Diagnosis, Prognosis and Prediction Using Histological and Cytological Images: A Systematic Review.

Lung cancer is one of the deadliest cancers worldwide, with a high incidence rate, especially in tobacco smokers. Lung cancer accurate diagnosis is based on distinct histological patterns combined with molecular data for personalized treatment. Precise lung cancer classification from a single H&E slide can be challenging for a pathologist, requiring most of the time additional histochemical and special immunohistochemical stains for the final pathology report. According to WHO, small biopsy and cytology specimens are the available materials for about 70% of lung cancer patients with advanced-stage unresectable disease. Thus, the limited available diagnostic material necessitates its optimal management and processing for the completion of diagnosis and predictive testing according to the published guidelines. During the new era of Digital Pathology, Deep Learning offers the potential for lung cancer interpretation to assist pathologists' routine practice. Herein, we systematically review the current Artificial Intelligence-based approaches using histological and cytological images of lung cancer. Most of the published literature centered on the distinction between lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung carcinoma, reflecting the realistic pathologist's routine. Furthermore, several studies developed algorithms for lung adenocarcinoma predominant architectural pattern determination, prognosis prediction, mutational status characterization, and PD-L1 expression status estimation.

Rotationplasty outcomes assessed by gait analysis following resection of lower extremity bone neoplasms.

Aims: The standard of surgical treatment for lower limb neoplasms had been characterized by highly interventional techniques, leading to severe kinetic impairment of the patients and incidences of phantom pain. Rotationplasty had arisen as a potent limb salvage treatment option for young cancer patients with lower limb bone tumours, but its impact on the gait through comparative studies still remains unclear several years after the introduction of the procedure. The aim of this study is to assess the effect of rotationplasty on gait parameters measured by gait analysis compared to healthy individuals. Methods: The MEDLINE, Scopus, and Cochrane databases were systematically searched without time restriction until 10 January 2022 for eligible studies. Gait parameters measured by gait analysis were the outcomes of interest. Results: Three studies were eligible for analyses. Compared to healthy individuals, rotationplasty significantly decreased gait velocity (-1.45 cm/sec; 95% confidence interval (CI) -1.98 to -0.93; p < 0.001), stride length (-1.20 cm; 95% CI -2.31 to -0.09; p < 0.001), cadence (-0.83 stride/min; 95% (CI -1.29 to -0.36; p < 0.001), and non-significantly increased cycle time (0.54 sec; 95% CI -0.42 to 1.51; p = 0.184). Conclusion: Rotationplasty is a valid option for the management of lower limb bone tumours in young cancer patients. Larger studies, with high patient accrual, refined surgical techniques, and well planned rehabilitation strategies, are required to further improve the reported outcomes of this procedure.

Modelling the COVID-19 pandemic: Focusing on the case of Greece.

The SARS-CoV-2 infection (COVID-19) pandemic created an unprecedented chain of events at a global scale, with European counties initially following individual pathways on the confrontation of the global healthcare crisis, before organizing coordinated public vaccination campaigns, when proper vaccines became available. In the meantime, the viral infection outbreaks were determined by the inability of the immune system to retain a long-lasting protection as well as the appearance of SARS-CoV-2 variants with differential transmissibility and virulence. How do these different parameters regulate the domestic impact of the viral epidemic outbreak? We developed two versions of a mathematical model, an original and a revised one, able to capture multiple factors affecting the epidemic dynamics. We tested the original one on five European countries with different characteristics, and the revised one in one of them, Greece. For the development of the model, we used a modified version of the classical SEIR model, introducing various parameters related to the estimated epidemiology of the pathogen, governmental and societal responses, and the concept of quarantine. We estimated the temporal trajectories of the identified and overall active cases for Cyprus, Germany, Greece, Italy and Sweden, for the first 250 days. Finally, using the revised model, we estimated the temporal trajectories of the identified and overall active cases for Greece, for the duration of the 1230 days (until June 2023). As shown by the model, small initial numbers of exposed individuals are enough to threaten a large percentage of the population. This created an important political dilemma in most countries. Force the virus to extinction with extremely long and restrictive measures or merely delay its spread and aim for herd immunity. Most countries chose the former, which enabled the healthcare systems to absorb the societal pressure, caused by the increased numbers of patients, requiring hospitalization and intensive care.

Variant-Related Differences in Laboratory Biomarkers among Patients Affected with Alpha, Delta and Omicron: A Retrospective Whole Viral Genome Sequencing and Hospital-Setting Cohort Study.

During the COVID-19 pandemic, different SARS-CoV-2 variants of concern (VOC) with specific characteristics have emerged and spread worldwide. At the same time, clinicians routinely evaluate the results of certain blood tests upon patient admission as well as during hospitalization to assess disease severity and the overall patient status. In the present study, we searched for significant cell blood count and biomarker differences among patients affected with the Alpha, Delta and Omicron VOCs at admission. Data from 330 patients were retrieved regarding age, gender, VOC, cell blood count results (WBC, Neut%, Lymph%, Ig%, PLT), common biomarkers (D-dimers, urea, creatinine, SGOT, SGPT, CRP, IL-6, suPAR), ICU admission and death. Statistical analyses were performed using ANOVA, the Kruskal-Wallis test, two-way ANOVA, Chi-square, T-test, the Mann-Whitney test and logistic regression was performed where appropriate using SPSS v.28 and STATA 14. Age and VOC were significantly associated with hospitalization, whereas significant differences among VOC groups were found for WBC, PLT, Neut%, IL-6, creatinine, CRP, D-dimers and suPAR. Our analyses showed that throughout the current pandemic, not only the SARS-CoV-2 VOCs but also the laboratory parameters that are used to evaluate the patient's status at admission are subject to changes.

The Gifted Rating Scales - School Form in Greek elementary and middle school learners: a closer insight into their psychometric characteristics.

The Gifted Rating Scales - School Form (GRS-S), an evaluation tool for the identification of gifted elementary and middle school children, was the subject of the current study, which focused on its psychometric features (internal consistency reliability and structural validity). Four hundred and eighty-nine teachers (342 women, 139 men, and 8 without gender declaration) used the GRS-S to estimate the dimensions of giftedness in their students for the current study. Particularly, 489 children (253 girls and 236 boys) were evaluated by their teachers. Eight elementary and middle school classes and sixteen 6-month age bands were used to stratify the student population. The scales' outstanding internal consistency and good factorial validity were revealed by statistical analyses (EFA, CFA, and Cronbach's coefficients). According to the current research findings, the GRS-S as a reliable and valid assessment tool for identifying gifted students (by their teachers) within the Greek cultural environment.

Deep Learning on Histopathological Images for Colorectal Cancer Diagnosis: A Systematic Review.

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men, with an increasing incidence. Pathology diagnosis complemented with prognostic and predictive biomarker information is the first step for personalized treatment. The increased diagnostic load in the pathology laboratory, combined with the reported intra- and inter-variability in the assessment of biomarkers, has prompted the quest for reliable machine-based methods to be incorporated into the routine practice. Recently, Artificial Intelligence (AI) has made significant progress in the medical field, showing potential for clinical applications. Herein, we aim to systematically review the current research on AI in CRC image analysis. In histopathology, algorithms based on Deep Learning (DL) have the potential to assist in diagnosis, predict clinically relevant molecular phenotypes and microsatellite instability, identify histological features related to prognosis and correlated to metastasis, and assess the specific components of the tumor microenvironment.

The Role of Digital Tools in the Timely Diagnosis and Prevention of Acute Exacerbations of COPD: A Comprehensive Review of the Literature.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways and lung parenchyma with multiple systemic manifestations. Exacerbations of COPD are important events during the course of the disease, as they are associated with increased mortality, severe impairment of health-related quality of life, accelerated decline in lung function, significant reduction in physical activity, and substantial economic burden. Telemedicine is the use of communication technologies to transmit medical data over short or long distances and to deliver healthcare services. The need to limit in-person appointments during the COVID-19 pandemic has caused a rapid increase in telemedicine services. In the present review of the literature covering published randomized controlled trials reporting results regarding the use of digital tools in acute exacerbations of COPD, we attempt to clarify the effectiveness of telemedicine for identifying, preventing, and reducing COPD exacerbations and improving other clinically relevant outcomes, while describing in detail the specific telemedicine interventions used.

Prosthetic reconstruction following resection of lower extremity bone neoplasms: A systematic review and meta-analysis.

Prosthetic reconstructive procedures have become the mainstay in contemporary surgical treatment following resection of extremity bone neoplasms. Given that these patients are of young age most of the time, achievement of robust functional outcomes is of paramount importance. The aim of this study is to assess the impact of this procedure on the gait parameters of cancer patients compared to healthy individuals. The Medline, Scopus and Cochrane databases were systematically searched until January 2022 for eligible studies. Gait parameters measured by gait analysis after prosthetic reconstruction were the outcomes of interest. Eight cohort studies were included in our analysis. From these, seven studied prosthetic reconstruction of the knee (distal femur or proximal tibia) and only one exclusively studied prostetic reconstructions of the proximal femur. Compared to healthy individuals a significant decrease was evident in gait velocity (-0.16 m/sec, 95 %CI: -0.23 to -0.09, p-value < 0.001), in stride length (-6.07 %height, 95 %CI: -9,36 to -2.78, p-value < 0.001), in cadence (-3.96 stride/min, 95 %CI: -5.41 to -2.51, p-value < 0.001) and significant increase in cycle time (0.10 s, 95 %CI: 0.03 to 0.17, p-value = 0.005). Prosthetic reconstruction following lower limb tumor resection significantly affects the gait of patients. This knowledge can be utilized for further refinement of surgical techniques, rehabilitation strategies and follow-up programming.

The Role and Effectiveness of Photodynamic Therapy on Patients With Actinic Keratosis: A Systematic Review and Meta-Analysis.

Actinic keratoses (AKs) are the most common neoplastic lesions and are recognized as a precursor to squamous cell skin cancer. Photodynamic therapy (PDT) is a therapeutic option for multiple AKs in line with field cancerization. The aim of this study was to assess the effectiveness of PDT on patients with AKs using a meta-analysis, in order to evaluate the possible superiority of one treatment over the others. For this purpose, the PubMed, MEDLINE, Scopus, OVID, Science Direct, British Journal of Dermatology, Research Gate, and Embase databases were searched in March 2022. The search terms used were 'photodynamic therapy' and 'actinic keratosis'. We utilized the random-effects meta-analysis model to compare methyl aminolevulinate PDT (MAL-PDT) and the combination of a nanoscale-lipid vesicle formulation with the prodrug 5-aminolevulinic acid (BF-200 ALA) on a complete response (CR) of the lesions. Our meta-analysis indicated that the comparison of BF-200 ALA versus MAL-PDT showed marginally higher CRs than MAL-PDT.

The Gifted Rating Scales-Preschool/Kindergarten Form (GRS-P): A Preliminary Examination of Their Psychometric Properties in Two Greek Samples.

The present paper is based on data of two samples concerning the Gifted Rating Scales-Preschool/Kindergarten Form (GRS-P) that aimed to gain insight into the psychometric properties (internal consistency reliability, structural and convergent validity) of the Greek version of the GRS-P. In both studies, teachers estimated their students' giftedness with the GRS-P and executive functions with the Childhood Executive Functioning Inventory (Study 1). In Study 2, kindergarteners were examined in cognitive measurements which included the colored progressive matrices, the children category test, the Athena test, and the mini-mental state examination. Statistical analyses (EFA, CFA, Cronbach's α, and Pearson's r coefficients) revealed the excellent internal consistency of the scales as well as their good factorial and convergent/discriminant validity. In relation to the children's cognitive ability measures, it emphasized the fact that the GRS-P is a reliable and valid tool for teachers to assess their gifted students in a Greek cultural context.

Cigarette Smoking, Coffee Consumption, Alcohol Intake, and Risk of Crohn's Disease and Ulcerative Colitis: A Mendelian Randomization Study.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are widely associated with smoking in epidemiological studies, whereas there are conflicting results for the association between CD and UC for both coffee and alcohol consumption. Herein, we aimed to investigate whether cigarette smoking and alcohol and coffee consumption are causally associated with either CD or UC. METHODS: We utilized 540 genome-wide significant single-nucleotide polymorphisms for 3 potentially addictive substances-nicotine, alcohol, and caffeine-to assess the association of smoking, coffee, and alcohol consumption with CD and UC (12,194 CD cases, 12,366 UC cases, and 25,042 controls of European ancestry), using Mendelian randomization analysis. Mendelian randomization estimates were used to evaluate the effect of the exposure factors on CD and UC risk. Sensitivity analysis was employed to test for any directional pleiotropy. RESULTS: We found evidence for a positive causal association between the age of smoking initiation and UC risk and between alcohol consumption and CD risk, which disappeared after sensitivity analysis for both associations (P > 0.05). No evidence for a causal association between cigarettes per day, smoking initiation, smoking cessation, and coffee consumption variables and UC or CD was found. CONCLUSIONS: We found no clear evidence that either genetically predicted smoking, coffee consumption, or alcohol consumption are causally associated with the risk for CD or UC, although our findings indicate a potential positive association between the age of smoking and UC and between alcohol consumption and CD.

The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study.

AIMS: Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. METHODS AND RESULTS: Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P < 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P < 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded. CONCLUSIONS: The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population.