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.

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.

Altered Fibrin Clot Properties Predict Stroke and Bleedings in Patients With Atrial Fibrillation on Rivaroxaban.

Background and Purpose- We investigated whether clot permeability can predict clinically relevant outcomes in patients with atrial fibrillation (AF) treated with rivaroxaban. Methods- In the cohort study, we enrolled 232 consecutive patients with AF on rivaroxaban 20 mg/d (76.3%) or 15 mg/d (23.7%) for at least 3 months. Plasma clot permeability (Ks), a measure of fibrin network density, was determined 24 to 30 hours since the intake of rivaroxaban at undetectable drug's levels. Ischemic cerebrovascular events and bleedings were recorded. Results- During a median follow-up of 48 months, patients with Ks below median (6.8 cm2·10-9) had higher prevalence of stroke (5.84 versus 0.88% per year; P<0.0001) and relevant bleeding (7.06 versus 0.88% per year; P<0.0001) compared with those above median. The mortality rate was 1.53% per year and was not associated with Ks. Lower Ks predicted cerebrovascular ischemic events (hazard ratio, 6.64; 95% CI, 2.2-20.1) and relevant bleedings (hazard ratio, 7.38; 95% CI, 2.58-21.10). Minor bleeds (32.8% of patients) were observed more often in patients with Ks above median (50.9 versus 14.7%; P<0.0001). Multivariate Cox regression analysis showed that in AF patients on rivaroxaban lower Ks increased the risk of stroke (hazard ratio, 6.51; 95% CI, 2.14-19.75) and relevant bleedings (hazard ratio, 9.68; 95% CI, 3.21-29.18). Conclusions- Decreased clot permeability in AF patients can predict thromboembolic and clinically relevant bleeding events during therapy with rivaroxaban, while looser clot networks predispose to minor bleeds.

Poorly differentiated thyroid cancer in the context of the revised 2015 American Thyroid Association Guidelines and the Updated American Joint Committee on Cancer/Tumor-Node-Metastasis Staging System (eighth edition).

OBJECTIVE: Poorly differentiated thyroid cancer (PDTC) is a rare, but aggressive thyroid cancer (TC) and a main cause of death from non-anaplastic follicular cell-derived TC. Assessing the risk of PDTC-related death and the risk of recurrence is important for clinicians. The recent American Thyroid Association (ATA) 2015 guidelines and the updated 8th edition of the American Joint Committee on Cancer/Tumor-Node-Metastasis (AJCC/TNM) staging system should support clinicians in the management approach to PDTC patients. PATIENTS: Forty-six consecutive PDTC patients treated in a single oncologic centre, 2000-2017. MEASUREMENTS: Retrospective analysis of TNM stage, initial risk, response-to-therapy categories, follow-up and final disease status incorporating the ATA 2015 criteria and the 8th AJCC/TNM staging system. Disease-specific survival (DSS) using the Kaplan-Meier method. RESULTS: Of the 46 PDTC 21 (45.6%) were ATA high risk (HR), 22 (47.8%), 17 (37%) and seven (15.2%) were TNM stages I, II, and III-IV, respectively. During a median follow-up of 55.5 months, two (4.3%) patients were recurrent, 18 (39.1%) died of PDTC. The 5-/10-year DSS were 65/57%, respectively. According to the AJCC/TNM, the 5-/10-year DSS of I, II, and III-IV stage were 83/83%; 77/55%, and 0/0%, respectively. According to the 2015 ATA initial risk, the 5-/10-year DSS were 91/72% for ATA intermediate risk and 38/38% for ATA HR patients. CONCLUSIONS: In PDTC patients, the updated AJCC/TNM staging system accurately predicts a high risk of death in stage III-IV, whereas it seems to be inadequate for predicting a very low or low risk of death expected for differentiated TC in stage I-II. The ATA initial HR may be also used to predict a high risk of PDTC-related death.

Somatic mutations in BRCA1&2 in 201 unselected ovarian carcinoma samples - single institution study.

Ovarian cancer (OC) is the most lethal among gynecologic malignancies worldwide. Unfortunately, in around 70% of cases cancer is diagnosed in late stages (III-IV) which decreases the 5-year survival rate to 25%. The standard of care in ovarian cancer is debulking surgery followed by chemotherapy regimens based on platinum salts. Since 2014 PARP inhibitors became available for OC patients with germline or/and somatic mutations in BRCA1/2, including maintenance therapy. BRCA1/2 Next Generation Sequencing (NGS)-based analysis of formalin-fixed paraffin-embedded (FFPE) ovarian cancer samples becomes the standard of care. The aim of the present study was to evaluate the frequency of mutations in 201 unselected ovarian cancer tissues using the NGS method. In total, pathogenic mutations in both genes were detected in 24% (49/201) of the ovarian cancer cases tested. For 41 patients the results of testing of DNA isolated from blood sample revealed that 17% (35/201) mutations were germline origin, whereas 3% (6/201) mutations were somatic. In 4% (8/201) cases blood sample was inaccessible. The presence of pathogenic mutations was correlated with younger age at diagnosis and serous subtype. Close cooperation between many specialists (gynecologist, pathologist, oncologist, clinical genetics and molecular biologist) is indispensable for efficient and on-time BRCA1/2 ovarian tumor tissue testing.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Thrombocytopenia.

AIMS: Thrombocytopenia was one of the exclusion criteria in randomized trials in which non-vitamin K antagonist oral anticoagulants (NOACs) were tested. The safety of NOACs in patients with atrial fibrillation (AF) and thrombocytopenia remains unclear. METHODS: We studied 62 patients with AF aged from 53 to 85 (mean 70.5) years with platelet count from 50 to 100 × 109/L who were treated with rivaroxaban 15 mg once daily (33.9%), dabigatran 110 mg twice daily (bid) (54.8%), or apixaban 2.5 mg bid (11.3%). Age- and sex-matched AF patients with normal platelet count and similar CHA2DS2-VASc scores who were treated with the recommended doses of NOACs served as a reference group. RESULTS: Patients were followed for a mean of 55 months (range, 23-64 months). In the thrombocytopenia group bleeding risk was higher (mean HAS-BLED score 2.0, vs. 1.0, P < 0.0001). During follow-up in thrombocytopenic and normocytopenic patients, we observed similar rates of major bleeding (1.8%/year vs. 2.7%/year, P = 0.49), clinically relevant nonmajor bleeding (CRNMB) (1.5%/year vs. 1.1%/year, P = 0.74), ischemic stroke and transient ischemic attacks (1.8%/year vs. 1.5%/year, P = 0.8), and death (1.06%/year vs. 1.11%/year, P = 0.96). The risk of bleeding and stroke was unaffected by the type of the NOAC used in both groups. Major bleedings and clinically relevant nonmajor bleeding in thrombocytopenic patients on NOACs were predicted only by age (hazard ratio 1.1, 95% confidence interval 1.0-1.3, P = 0.04). CONCLUSIONS: Our findings indicate that in AF patients with mild thrombocytopenia, anticoagulation with NOAC at reduced doses seems to be safe and effective.

Novel tool in rheumatoid arthritis diagnosis-The usage of urease flap region peptidomimetics.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease. Early diagnosis can prevent joint erosion. However, available biomarkers do not always allow for clear distinction between RA and non-RA individuals. It has become known that bacteria/viruses are among the environmental triggers that initiate RA via multiple molecular mechanisms. Thus, to better understand the role of bacteria in RA, we synthetized 6 peptidomimetics of bacterial ureases' flap region. These peptides were then used to distinguish RA patients from healthy people sera by immunoblotting. Most patients' sera were bound to peptidomimetic characteristic for Enterobacter sp. and Klebsiella sp. flap urease. We also found similarities between peptidomimetic sequence and human proteins connected with RA. This pilot study suggests that bacteria may trigger RA via mechanism of molecular mimicry of urease to host proteins and ureases flap peptidomimetics may be potential candidate as a new additional diagnostic test.

Response to therapy of papillary thyroid cancer of known BRAF status.

OBJECTIVE: A dynamic risk stratification with modified initial estimated risk based on response to therapy and disease course is one of the crucial changes adopted recently by the American Thyroid Association (ATA). This approach focuses on an individualized risk-adapted approach to the management of differentiated thyroid cancer. The BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). However, the prognostic value of this mutation remains unclear. The aim of this study was to examine the relation between the BRAF V600E status in PTC and all ATA response-to-therapy categories, as well as the recurrence and persistence of both biochemical disease and structural disease. PATIENTS: Unselected PTC cases with known BRAF status diagnosed from 2000 to 2013 and actively monitored at one institution (n=723) were reviewed retrospectively. The association between the BRAF V600E mutation and clinicopathological characteristics, ATA 2015 response-to-therapy category, recurrence after a period of no evidence of disease (NED) and persistent biochemical or structural disease, was analysed. RESULTS: BRAF V600E was found in 65.7% (475/723) of PTC cases. Although BRAF mutation status correlated significantly with certain clinicopathological prognostic factors, there was no correlation with any of the response-to-therapy categories. Recurrences and persistent biochemical or structural disease were not associated with BRAF status. CONCLUSIONS: Our data are consistent with those of other studies reporting a positive relation between BRAF V600E mutation and poor prognostic factors in PTC; however, the BRAF status did not significantly correlate with a response to therapy.

A new look at the drug-resistance investigation of uropathogenic E. coli strains.

Bacterial drug resistance and uropathogenic tract infections are among the most important issues of current medicine. Uropathogenic Escherichia coli strains are the primary factor of this issue. This article is the continuation of the previous study, where we used Kohonen relations to predict the direction of drug resistance. The characterized collection of uropathogenic E. coli strains was used for microbiological (the disc diffusion method for antimicrobial susceptibility testing), chemical (ATR/FT-IR) and mathematical (artificial neural networks, Ward's hierarchical clustering method, the analysis of distributions of inhibition zone diameters for antibiotics, Cohen's kappa measure of agreement) analysis. This study presents other potential tools for the epidemiological differentiation of E. coli strains. It is noteworthy that ATR/FT-IR technique has turned out to be useful for the quick and simple identification of MDR strains. Also, diameter zones of resistance of this E. coli population were compared to the population of E. coli strains published by EUCAST. We observed the bacterial behaviors toward particular antibiotics in comparison to EUCAST bacterial collections. Additionally, we used Cohen's kappa to show which antibiotics from the same class are closely related to each other and which are not. The presented associations between antibiotics may be helpful in selecting the proper therapy directions. Here we present an adaptation of interdisciplinary studies of drug resistance of E. coli strains for epidemiological and clinical investigations. The obtained results may be some indication in deciding on antibiotic therapy.

Use of Fourier-transform infrared spectroscopy in the diagnosis of rheumatoid arthritis: a pilot study.

Rheumatoid arthritis is an autoimmune inflammatory disease leading to joint cartilage, bone degradation and limitation of mobility. Diagnosis of RA is difficult and complex. There are also no effective methods for clear discrimination between RA patients and non-RA individuals. In this work we use IR spectroscopy to differentiate RA patients and blood donors' sera. We found differences between investigated sera (RA and non-RA) in range of 3000-2800 and 1800-800 cm-1 (W1-W5 regions). Based on mathematical analysis we developed a K-NN model characterized by 85 % of sensitivity and 100 % of specificity. Also we found that, wavenumber 1424 cm-1, comprising in W3 region, was the most effective in human sera distinguishing. We conclude that IR spectroscopy may serve as a fast and easy method useful in RA serology.

Detection of ureolytic activity of bacterial strains isolated from entomopathogenic nematodes using infrared spectroscopy.

The pathogenicity of entomopathogenic nematodes (EPNs) depends directly on the presence of bacteria in the nematode digestive tracts. Based on 16S rRNA and MALDI-TOF analyses 20 isolated bacteria were assigned to 10 species with 10 isolates classified as Pseudomonas ssp. Six strains (30%) show ureolytic activity on Christensen medium. Spectroscopic analysis of the strains showed that the ureolytic activity is strongly correlated with the following wavenumbers: 935 cm(-1) in window W4, which carries information about the bacterial cell wall construction and 1158 cm(-1) in window W3 which corresponds to proteins in bacterial cell. A logistic regression model designed on the basis of the selected wavenumbers differentiates ureolytic from non-ureolytic bacterial strains with an accuracy of 100%. Spectroscopic studies and mathematical analyses made it possible to differentiate EPN-associated Pseudomonas sp. strains from clinical Pseudomonas aeruginosa PAO1. These results suggest, that infrared spectra of EPN-associated Pseudomonas sp. strains may reflect its adaptation to the host.

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.

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.

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.

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.

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.

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.

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.

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.