Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients.

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.

The Frequency of Differentiated Thyroid Cancer Recurrence in 2302 Patients With Excellent Response to Primary Therapy.

CONTEXT: Discrepant data on the recurrence rate of differentiated thyroid cancer (DTC) are reported. OBJECTIVE: To evaluate the frequency and risk factors of true recurrence in DTC patients with excellent responses (ExR) to initial therapy. METHODS: A retrospective analysis of the 2302 consecutive DTC patients with ExR to primary therapy, treated during 24 years at single center. The percentage of recurrence and cumulative recurrence rate (CRR) were analyzed. Risk factors for recurrence for patients with papillary thyroid cancer (PTC) were investigated and methods for establishing a diagnosis of recurrence were evaluated. RESULTS: Of DTC patients, 32 (1.4%) experienced recurrence. PTC patients with recurrence were more likely to have younger age (P = .0182), larger tumor size (P = .0013), lymph node metastases (P = .0013), incomplete resection (P = .0446), higher ATA risk (P = .0002), and had more frequently been treated with 131I (P = .0203). CRRs at 5, 10, 15, 20, and 24 years after surgery were 1.2%, 1.9%, 2.5%, 2.9%, and 2.9%, respectively. The CRRs according to histological type were highest for poorly differentiated thyroid cancer (PDTC), lower for oncocytic (OTC) and follicular thyroid cancer (FTC), and lowest for PTC. Most recurrences occurred within the first 5 years of observation. The most effective method for detecting local recurrence was ultrasonography with fine needle aspiration cytology, and for distant metastases, 18F-FDG PET. CONCLUSION: True recurrence is rare in DTC patients. PTC patients with ExR to primary therapy and N0/Nx can be dismissed from oncological follow-up. Despite ExR to primary therapy, DTC patients with N1, and PDTC, OTC, FTC should remain under oncological follow-up.

CD276 as a Candidate Target for Immunotherapy in Medullary Thyroid Cancer.

Medullary thyroid cancer (MTC) is a rare malignancy, and the treatment of metastatic MTC is challenging. In previous work, immune profiling (RNA-Seq) of MTC identified CD276 as a potential target for immunotherapy. CD276 expression was 3-fold higher in MTC cells than in normal tissues. Paraffin blocks from patients with MTC were analyzed by immunohistochemistry to confirm the results of RNA-Seq. Serial sections were incubated with anti-CD276 antibody, and scored according to staining intensity and the percentage of immunoreactive cells. The results showed that CD276 expression was higher in MTC tissues than in controls. A lower percentage of immunoreactive cells correlated with the absence of lateral node metastasis, lower levels of calcitonin after surgery, no additional treatments, and remission. There were statistically significant associations of intensity of immunostaining and percentage of CD276 immunoreactive cells with clinical factors and the course of the disease. These results suggest that targeting this immune checkpoint molecule CD276 could be a promising strategy for the treatment of MTC.

The Levels of Anti-SARS-CoV-2 Spike Protein IgG Antibodies Before and After the Third Dose of Vaccination Against COVID-19.

Purpose: The COVID-19 pandemic has been going on for almost three years, and so far, many preventive and therapeutic strategies have been developed. The issue of subsequent booster vaccinations is currently being discussed. We aimed to analyze how the third dose of vaccination against COVID-19 correlates with the dynamics of IgG anti-SARS-CoV-2 spike protein antibody levels in a group of healthy people. Patients and Methods: The prospective study included 93 participants before and after a second booster of COVID-19 vaccination, from whom 4 blood samples were collected at intervals. The levels of IgG anti-SARS-CoV-2 in serum were identified using the chemiluminescent immunoassay specific for the receptor-binding domain (RBD) of the S1 protein. The analysis of the results was performed using appropriate statistical methods, considering p <0.05 as a statistically significant value. Results: The IgG levels were significantly higher and less diverse after the same follow-up time from the second booster vaccination compared to the first booster. The antibody levels were positively correlated with female, healthcare workers, the elderly and participants with a negative COVID-19 history. Furthermore, the increase in IgG antibodies after the second booster vaccination correlated inversely with the baseline level of antibodies before the vaccination. The latest results showed that antibody levels dropped 1.5-fold after approx. 10 months from the second booster vaccination but still remained at a protective level. Conclusion: Booster vaccinations seem to better stimulate immune memory, and in the case of borderline IgG level induces the greatest increase in antibodies. It is worth considering the individual parameters of patients and measuring antibodies before vaccination.

Elective cardioversion of atrial fibrillation is safe without transesophageal echocardiography in patients treated with non-vitamin K antagonist oral anticoagulants: Multicenter experience.

BACKGROUND: Current guidelines recommend electrical cardioversion (ECV) in patients with atrial fibrillation (AF) after at least 3 weeks of adequate non-vitamin K antagonist oral anticoagulant (NOAC) treatment without prior transesophageal echocardiography (TEE). However, in clinical practice in some centres, TEE is performed before ECV in patients with AF. The aim of the study was to evaluate prevalence of thromboembolic and hemorrhagic complications in patients with AF treated with NOACs and undergoing ECV without prior TEE. METHODS: This observational, multicentre study included consecutive patients with AF treated with NOACs who were admitted for ECV without prior TEE. Thromboembolic events and major bleeding complications were investigated during a 30-day follow-up. RESULTS: In the study group there were 611 patients, mean age was 66.3 ± 9.2 years, 40% were women. 52 (8.5%) patients had a low thromboembolic risk, 148 (24.2%) patients had an intermediate thromboembolic risk and 411 (67.2%) patients had a high thromboembolic risk. In the study group 253 (41.4%) patients were treated with rivaroxaban, 252 (41.2%) patients were treated with dabigatran and 106 (17.3%) patients were treated with apixaban. Reduced doses of NOACs were administered to 113 (18.9%) patients. In the entire study group, there were no thromboembolic events or major bleeding complications during the in-hospital stay and the 30-day follow-up. CONCLUSIONS: In this "real-world" study of AF patients treated with NOACs, it was proved that ECV is safe without a preceding TEE, regardless of the risk of thromboembolic complications and of the type of NOAC used.

A Significance of Concomitant BRAFV600E and TERT Mutations in Polish Patients with Papillary Thyroid Microcarcinoma: A Retrospective Cohort Study Based on 430 Cases.

Background: The incidence of papillary thyroid cancer is increasing worldwide due to more frequent pathological detection of papillary thyroid microcarcinomas (PTMC), which are cancers measuring 1 cm or less in diameter. In rare cases, the course of PTMC can be aggressive, with an increased risk of recurrence/persistent disease. The aim of this study of Polish patients diagnosed with PTMC was to assess the impact of concomitant B-type Raf kinas-activating mutation in codon 600 of exon 15 (BRAFV600E) and telomerase reverse transcriptase (TERT) hotspot mutations on clinicopathological features, response to treatment, potential recurrence, and the final outcome. Methods: A retrospective analysis of the 430 PTMC cases diagnosed during 2001-2020 at a single center was performed. All PTMC cases were assessed histopathologically, and analyses of BRAFV600E and TERT promoter were performed based on DNA isolated from tumor blocks. Results: There were 29/430 (6.7% [confidence interval: 4.6-9.5]) patients in whom the TERTC228T and/or TERTC250T mutations coexisted with the BRAFV600E mutation. A statistical comparison between PTMC cases with concomitant BRAFV600E and TERT hotspot mutations and those without any of those mutations revealed no significant differences between the two groups with respect to risk stratification, response to primary treatment, clinical course, or final disease status. Conclusion: Regardless of the molecular background of PTMC, the overall response to therapy is excellent, and long-term disease-free survival rates can be achieved by most patients.

Temporal Trends in Oral Anticoagulant Prescription in Atrial Fibrillation Patients between 2004 and 2019.

BACKGROUND: In the recent years, antithrombotic prophylaxis in patients with atrial fibrillation (AF) has changed significantly. The main aim of this study is to assess the temporal trends of antithrombotic therapy and identify factors predisposing oral anticoagulant (OAC) use in stroke prevention in AF patients. METHODS: The present study is a retrospective, observational, single-center study, which includes consecutively hospitalized patients in the reference cardiology center from January 2004 to December 2019. RESULTS: A total of 9656 patients (43.7% female, mean age 71.2 years) with AF between 2004-2019 are included. Among the total study population, in most of the patients (81.1%), OAC therapy was used, antiplatelet (APT) therapy was prescribed for 13.5% patients, heparins for 2.1% patients and 3.3% of patients did not receive any stroke prevention. OAC prescription significantly increased from 61.6% in 2004 to 97.4% in 2019. The independent predictors of OAC prescription were: the period of hospitalization, non-paroxysmal AF, age, hypertension, diabetes mellitus, previous thromboembolism, hospitalization due to electrical cardioversion, ablation or AF without any procedures. CONCLUSIONS: In hospitalized patients with AF, during sixteen years of the study period, a significant increase in OAC use and a decrease in APT use were noted. Factors other than these included in the CHA2DS2-VASc score were independent predictors of OAC use.

Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals?

Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.

Immune Profiling of Medullary Thyroid Cancer-An Opportunity for Immunotherapy.

Medullary thyroid cancer (MTC) is a rare malignancy that arises from calcitonin-producing C-cells. Curative treatment for patients with metastatic MTC is challenging. Identifying the mechanisms by which cancer cells inhibit the activity of immune cells provides an opportunity to develop new therapies that restore anticancer activity. Little is known about the immunological phenomena underlying MTC. Here, we examined the expression profile of 395 genes associated with MTC. The study included 51 patients diagnosed with MTC at a single center. Bioinformatical analysis revealed that CD276 expression in MTC cells was at least three-fold higher than that in normal tissue. The expression of CD276 showed a weak but statistically significant positive correlation with tumor diameter, but we did not find a significant association between CD276 expression and other histopathological clinical factors, or the response to initial therapy. A search of published data identified the monoclonal antibody (inhibitor) enoblituzumab as a potential drug for patients diagnosed with MTC overexpressing CD276.

Genotype-specific versus pangenotypic regimens in patients infected with hepatitis C virus genotype 1b in real-world settings.

Introduction: The introduction of direct-acting antivirals (DAAs) has provided us with hope to eliminate hepatitis C virus (HCV) infection as a significant public health problem in the coming years. Objective: Our study aimed to compare the effectiveness and safety of genotype-specific and pangenotypic regimens in genotype 1b­infected patients treated in real-world settings. Patients and methods: Patients were selected from 990 HCV-infected individuals treated with DAAs in the Department of Infectious Diseases in Kielce, Poland, who had the therapy initiated between July 1, 2015 and December 31, 2020. Results: A total of 795 genotype 1b­infected patients with a median age of 51 years, female predominance (55%), and a 21.1% rate of cirrhosis were included in the analysis. A total of 69.9% of patients were treated with genotype-specific regimens. Those patients were significantly older, more often were treatment experienced, and had advanced liver fibrosis and cirrhosis compared with patients assigned to pangenotypic regimens. An overall sustained virologic response rate of 97.9% in the intention-to-treat (ITT) analysis and 99% after excluding nonvirologic nonresponders was achieved, with no significant difference between patients in the 2 treatment arms. Significantly higher proportions of men (P = 0.001) and DAA-experienced patients (P = 0.049) were documented among virologic nonresponders. Conclusions: We confirmed very high effectiveness and a good safety profile of both genotype-specific and pangenotypic regimens used in patients with genotype 1b HCV infection, and we found no differences between these 2 generations of medications. Male sex and previous treatment with DAAs were identified as negative predictors for therapy effectiveness.

Is Male Sex A Prognostic Factor in Papillary Thyroid Cancer?

Identifying risk factors is crucial for predicting papillary thyroid cancer (PTC) with severe course, which causes a clinical problem. The purpose of this study was to assess whether male sex can be such a predictive factor and to verify whether including it as a predictive factor of high initial risk of recurrence/persistence would help to enhance the value of the American Thyroid Association initial risk stratification system (ATA). We retrospectively analyzed 1547 PTC patients (1358 females and 189 males), treated from 1986 to 2018. The relationship between sex and clinicopathological features, response to therapy, and disease status was assessed. Men with PTC showed some adverse clinicopathological features more often than women, including angioinvasion, lymph node metastases, and tumor size > 40 mm. There were sex-related disparities with respect to response to initial therapy and final follow-up. Male sex is associated with some unfavorable clinicopathological features of PTC, which may affect response to initial therapy or final disease status. In our study, modification of the ATA system by including male sex as a risk factor does not enhance its value. Thus, further studies are needed to assess whether males require treatment modalities or oncological follow-up protocols that are different from those of females.

Right ventricular echocardiographic parameters associated with prothrombotic abnormalities in normotensive patients with acute pulmonary embolism.

BACKGROUND: In acute pulmonary embolism (PE) right ventricular (RV) pressure overload negatively affects prognosis. Recently we have shown that RV dilatation is associated with a prothrombotic state in PE. We investigated which RV echocardiographic parameters best indicate prothrombotic alterations in acute PE. METHODS: In 121 normotensive, noncancer PE patients, markers of RV dilatation and dysfunction were evaluated on admission using transthoracic echocardiography, along with prothrombotic state markers, i.e. increased endogenous thrombin generation (ETP), low fibrin clot permeability (Ks, a measure of clot density), and prolonged clot lysis time (CLT). RESULTS: RV parasternal long axis (RVOT PLAX) >30 mm was associated with ETP (OR 3.86; 95% CI 1.55-9.62; p = 0.004) and CLT (OR 4.08; 95% CI 1.58-10.54; p = 0.004) in the top quartiles, but not with Ks. RV short parasternal axis (RVOT PSAX) >27 mm showed similar associations with higher ETP (OR 3.54; 95% CI 1.50-8.37; p = 0.004) and prolonged CLT (OR 2.78; 95% CI 1.17-6.62; p = 0.021). RV basal diameter >41 mm solely predicted prolonged CLT (OR 2.93; 95% CI 1.23-6.99; p = 0.016). The right atrium area, pulmonary trunk diameter, and tricuspid regurgitation maximum velocity were not related to prothrombotic markers, except for tricuspid annular plane systolic excursion weakly associated with ETP. Multivariable analysis showed that RVOT PSAX is independently associated with prolonged CLT (OR 1.16; 95% CI 1.04-1.30; p = 0.007), low Ks (OR 1.21; 95% CI 1.02-1.44; p = 0.029), and higher ETP (OR 1.14; 95% CI 1.03-1.26; p = 0.009). CONCLUSIONS: Among RV echocardiographic parameters, the RVOT dilatation measured in PSAX best predicts prothrombotic alterations in PE patients.

Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma.

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.

Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation in secondary stroke and systemic embolism prevention.

BACKGROUND: Oral anticoagulants (OAC) are recommended in all patients with atrial fibrillation (AF) after thromboembolic events without contraindications. It is hypothesized herein, that the majority of patients with AF after thromboembolic events receive OAC and the presence of specific factors, predisposes the use of non-vitamin K antagonist oral anticoagulants (NOACs). METHODS: This is a retrospective study, encompassing patients with AF hospitalized in a reference cardiology center over the years 2014-2017. Thromboembolic events were defined as: ischemic stroke, transient ischemic attack and systemic embolism. Inclusion criteria were the following: diagnosis of non-valvular AF at discharge from hospital, hospitalization not resulting in death. RESULTS: Among 2834 hospitalized patients with AF, a history of thromboembolic events was identified in 347 (12.2%) patients. In the group studied, of 347 patients with AF after a thromboembolic event, 322 (92.8%) received OAC, including 133 patients on vitamin K antagonist (41.3% of patients on OAC) and 189 patients on NOACs (58.7% of patients on OAC). Among patients treated with NOACs the majority were on dabigatran (116 patients, 61.4%), followed by rivaroxaban (54 patients, 28.6%), and apixaban (19 patients, 10%). Multivariate logistic regression analysis demonstrated that the presence of arterial hypertension reduced the chance for NOACs use (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.9, p = 0.04) and left atrial size ≤ 40 mm was a factor increasing the chance for the use of NOACs (OR 2.5, 95% CI 1.1-5.8, p = 0.03). CONCLUSIONS: Nearly all hospitalized patients with AF received OAC in the secondary prevention of thromboembolic complications. NOACs were used for secondary prevention of stroke among patients with AF in patients with fewer comorbidities.

Pathogenic Factors Correlate With Antimicrobial Resistance Among Clinical Proteus mirabilis Strains.

Proteus mirabilis is the third most common etiological factor of urinary tract infection. It produces urease, which contributes to the formation of a crystalline biofilm, considered to be one of the most important virulence factors of P. mirabilis strains, along with their ability to swarm on a solid surface. The aim of this study was to analyze the pathogenic properties of two selected groups of clinical P. mirabilis isolates, antimicrobial susceptible and multidrug resistant (MDR), collected from hospitals in different regions in Poland. The strains were examined based on virulence gene profiles, urease and hemolysin production, biofilm formation, and swarming properties. Additionally, the strains were characterized based on the Dienes test and antibiotic susceptibility patterns. It turned out that the MDR strains exhibited kinship more often than the susceptible ones. The strains which were able to form a stronger biofilm had broader antimicrobial resistance profiles. It was also found that the strongest swarming motility correlated with susceptibility to most antibiotics. The correlations described in this work encourage further investigation of the mechanisms of pathogenicity of P. mirabilis.

Trends in the Prescription of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation: Results of the Polish Atrial Fibrillation (POL-AF) Registry.

BACKGROUND: Current guidelines do not suggest in which groups of patients with atrial fibrillation (AF) individual non-vitamin K antagonist oral anticoagulants (NOACs) should be used for the prevention of thromboembolic complications. The aim of this study was to evaluate the frequency of use of apixaban, dabigatran, and rivaroxaban, and attempt to identify factors predisposing their administration. METHODS: The Polish Atrial Fibrillation (POL-AF) registry is a prospective, non-interventional study, including consecutive patients with AF hospitalized in ten Polish cardiology centers during the period ranging from January to December 2019. In this study, all patients were treated with NOACs. RESULTS: Among the 2971 patients included in the analysis, 40.4% were treated with rivaroxaban, 32% with apixaban, and 27.6% with dabigatran. The mean age of the total population was 72 ± 11.5 years and 43% were female. A reduced dose of NOAC was used in 35% of patients treated with apixaban, 39.7% of patients treated with dabigatran, and 34.4% of patients treated with rivaroxaban. Independent predictors of the use of apixaban were previous bleeding (OR 2.37, CI 1.67­3.38), GFR < 60 mL/min (OR 1.38, CI 1.25­1.64), heart failure (OR 1.38, CI 1.14­1.67) and age (per 5 years) (OR 1.14, CI 1.09­1.19). GFR < 60 mL/min (OR 0.79, CI 0.66­0.95), female (OR 0.8, CI 0.67­0.96) and age (per 5 years) (OR 0.95, CI 0.91­0.99) diminished the chance of using dabigatran. Previous bleeding (OR 0.43, CI 0.28­0.64), vascular disease (OR 0.84, CI 0.70­0.99), and age (per 5 years) (OR 0.94, CI 0.90­0.97) diminished the chance of choosing rivaroxaban. CONCLUSIONS: In hospitalized patients with AF, the most frequently chosen NOAC was rivaroxaban. Apixaban was chosen more often in patients after bleeding, and in those who were advanced in years, with heart failure and impaired renal function. Impaired renal function and female gender were factors that diminished the chance of using dabigatran. Previous bleeding and vascular disease was the factor that diminished the chance of using rivaroxaban. Dabigatran and rivaroxaban have been used less frequently in elderly patients.

Left Atrial Appendage Thrombus Formation Despite Continuous Non-Vitamin K Antagonist Oral Anticoagulant Therapy in Atrial Fibrillation Patients Undergoing Electrical Cardioversion or Catheter Ablation: A Comparison of Dabigatran and Rivaroxaban.

Left atrial appendage thrombus (LAAT) may be detected by transesophageal echocardiography (TOE) in patients with atrial fibrillation (AF) despite continuous anticoagulation therapy. We examined the factors predisposing to LAAT in patients treated with the anticoagulants dabigatran and rivaroxaban. We retrospectively evaluated 1,256 AF patients from three centres who underwent TOE before electrical cardioversion (n = 611, 51.4%) or catheter ablation (n = 645, 48.6%) from January 2013 to December 2019 and had been on at least three weeks of continuous dabigatran (n = 603, 48%) or rivaroxaban (n = 653, 52%) therapy. Preprocedural TOE diagnosed LAAT in 51 patients (4.1%), including 30 patients (5%) treated with dabigatran and 21 patients (3.2%) treated with rivaroxaban (p=0.1145). In multivariate logistic regression, predictors of LAAT in patients treated with dabigatran were non-paroxysmal AF (vs. paroxysmal AF) (OR = 6.2, p=0.015), heart failure (OR = 3.22, p=0.003), and a eGFR <60 ml/min/1.73 m2 (OR = 2.65, p=0.012); the predictors in patients treated with rivaroxaban were non-paroxysmal AF (vs. paroxysmal AF) (OR = 5.73, p=0.0221) and heart failure (OR = 3.19, p=0.116). In ROC analysis of the dabigatran group, the area under the curve (AUC) for the CHA2DS2-VASc-RAF score was significantly higher (0.78) than those for the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores (0.67, 0.70, and 0.72, respectively). In the rivaroxaban group, the CHA2DS2-VASc-RAF score also performed significantly better (AUC of 0.77) than the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores (AUC of 0.66, 0.64, and 0.67, respectively). The risk of LAAT was the same for patients in both treatment groups. In all patients, non-paroxysmal AF or heart failure, and in patients treated with dabigatran an eGFR <60 ml/min/1.73 m2, were independent predictors of LAAT. The new CHA2DS2-VASc-RAF scale had the highest predictive value for LAAT in the entire study population.

Stroke prevention and guideline adherent antithrombotic treatment in elderly patients with atrial fibrillation: A real-world experience.

Patients aged ≥75 years with the diagnosis of atrial fibrillation (AF) are at a higher risk of stroke and, according to recent recommendations, should receive oral anticoagulant (OAC) therapy. This study aimed to assess the recommended prophylactic antithrombotic therapy among patients with AF aged ≥ 75 years and its compliance with current guidelines. We also aimed to identify predisposing factors associated with the administration of non-vitamin K antagonist oral anticoagulants (NOACs) in elderly patients with AF.This was a retrospective, single-center observational study. Patients with AF aged ≥75 years hospitalized at a reference cardiology center from 2014 to 2017 were included in the analysis.Among the 1236 eligible patients (43.4% male; mean age, 82 years), OACs were recommended in 90.1% of cases. Of these, 59.8% of patients used NOACs and 40.2% used vitamin K antagonists. Additionally, 3.3% of patients received antiplatelet (AP) therapy and 2.5% were administered low molecular weight heparin. Only 4.5% of patients did not receive any anticoagulant treatment. The majority (89.9%) of patients received relevant prophylactic antithrombotic therapy according to current guidelines; only 1.4% were overtreated and 8.7% were undertreated. The significant predictors of NOAC therapy among patients treated with anticoagulants were non-permanent AF (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.30-2.18, P = .0001), age-by 5 years (OR = 1.33, 95% CI = 1.16-1.52, P = .0001), and glomerular filtration rate-by 5 units (OR = 1.06, 95% CI = 1.02-1.10, P = .0066).A high percentage of AF patients aged ≥75 years receive OACs, mainly NOACs. Most patients are treated according to the current guidelines; under treatment is primarily observed in patients receiving AP therapy. Non-permanent AF, age, and preservation of renal function are significant predictors of NOAC use.

Does the CHA2DS2-VASc scale sufficiently predict the risk of left atrial appendage thrombus in patients with diagnosed atrial fibrillation treated with non-vitamin K oral anticoagulants?

The CHA2DS2-VASc scale does not include potential risk factors for left atrial appendage thrombus (LAAT) formation such as a form of atrial fibrillation (AF) and impaired kidney function. The real risk of thromboembolic complications in AF patients is still unclear as well as an optimal anticoagulant treatment in males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2.The aim of this study was to compare the predictive value of the CHA2DS2-VASc scale and other scales to estimate the risk of LAAT formation in AF patients treated with non-vitamin K oral anticoagulants (NOACs) and to assess the prevalence of thrombi in patients at intermediate risk of stroke.The observational study included consecutive patients with a diagnosis of non-valvular AF treated with NOACs, admitted to 3 high-reference institutions between 2013 and 2018. All individuals underwent transoesophageal echocardiography before cardioversion or ablation.Out of 1163 enrolled AF patients (62.1% male, mean age 62 years) the LAAT had been detected in 50 individuals (4.3%). Among patients with LAAT, 1 patient (2.0%) was classified as a low-risk category, 9 (18.0%) were at intermediate-risk, and 40 (80.0%) were at high risk of thromboembolic complications according to CHA2DS2-VASc scale. All patients were treated with NOACs: 51.0% rivaroxaban, 47.1% dabigatran, and 1.9% apixaban.Patients at intermediate stroke-risk with detected LAAT had higher R2CHADS2 score (2.1 ±â€Š1.2 vs 1.2 ±â€Š0.8, P = .007), higher CHA2DS2-VASc-RAF score (6.4 ±â€Š4.4 vs 3.7 ±â€Š2.6, P = .027) and more often had an estimated glomerular filtration rate below 56 mL/min/1.73 m (44.4% vs 13.2%, P = .026) compared to patients without LAAT. The receiver operating characteristics revealed that the CHA2DS2-VASc-RAF scale had better predictive ability to distinguish between patients with and without LAAT in the study group than CHA2DS2-VASc (P = .0006), CHADS2 (P = .0006) and R2CHADS2 scale (P = .0140).The CHA2DS2-VASc scale should be supplemented with an assessment of renal function and form of AF to improve stroke risk estimation. The application of additional scales to estimate the risk of LAAT might be especially useful among males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2.

Thrombus in the left atrial appendage in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants in clinical practice-A multicenter registry.

BACKGROUND: The prevalence and predictors of left atrial appendage thrombus (LAAT) in patients with non-valvular atrial fibrillation (AF) who have been treated with non-vitamin K antagonist oral anticoagulants (NOACs) are not well defined. We aimed to assess the occurrence and predictors of LAAT on transesophageal echocardiography (TOE) in patients with non-valvular AF treated with NOACs for at least 3 weeks. METHODS: Consecutive patients with non-valvular AF who underwent TOE before catheter ablation or electrical cardioversion in three high-reference centers between 2014 and 2018 were included. Patients on apixaban were excluded from the study due to low numbers in this category. All patients received NOACs for at least 3 weeks before TOE. RESULTS: A total of 1148 patients (female, 38.1%; mean age, 62.1 years) referred to our centers for catheter ablation of AF (52.1%) or electrical cardioversion (47.9%) were included. Patients were on rivaroxaban (51.9%) or dabigatran (48.1%). Preprocedural TOE revealed LAAT in 4.4% of all patients. Multivariable logistic regression analysis showed the CHA2DS2-VASc score ≥2 points (OR = 2.11; 95% CI, 1.15-3.88; P = .0161), non-paroxysmal AF (OR = 6.30; 95% CI, 2.22-17.91; P = .0005), and GFR <60 mL/min/1.73 m2 (OR = 2.05; 95% CI, 1.14-3.67; P = .0160) were independent predictors of LAAT in patients treated with NOACs. CONCLUSIONS: In non-valvular AF patients treated with NOACs, the prevalence of LAAT was 4.4% before electrical cardioversion or ablation. In addition to the CHA2DS2-VASc score, the type of AF and renal function should be considered in the stratification of thromboembolism risk in AF patients and qualification for a preprocedural TOE.