In this study, we examined the relationship between coexisting BRAF V600E and TERT promoter mutations in papillary thyroid cancer (PTC) and response to therapy. PTC cases (n = 568) with known BRAF and TERT status, diagnosed from 2000 to 2012 and actively monitored at one institution, were reviewed retrospectively. Associations between BRAF V600E and TERT promoter mutations and clinicopathological features, Tumor-Node-Metastasis stage, initial risk, response to therapy, follow-up, and final disease outcome were assessed according to American Thyroid Association 2015 criteria and the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system. Median follow-up was 120 months. TERT promoter mutations (any type) were detected in 13.5% (77/568) of PTC cases with known BRAF status. The C228T and C250T TERT hotspot mutations were found in 54 (9.5%) and 23 (4%) patients, respectively, and 22 other TERT promoter alterations were identified. Coexisting BRAF V600E and TERT hotspot promoter mutations were detected in 9.5% (54/568) of patients, and significantly associated with older patient age (P = 0.001), gross extrathyroidal extension (P = 0.003), tumor stage pT3-4 (P = 0.005), stage II to IV (P = 0.019), intermediate or high initial risk (P = 0.003), worse than excellent response to primary therapy (P = 0.045), recurrence (P = 0.015), and final outcome of no remission (P = 0.014). We conclude that coexisting BRAF V600E and TERT mutations in patients with PTC are associated with poor initial prognostic factors and clinical course and may be useful for predicting a worse response to therapy, recurrence, and poorer outcome than in patients without the above mutations.

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.

Background: Thyroid cancer (TC) has one of the fastest increasing incidences worldwide and primarily involves papillary thyroid cancer (PTC). The BRAF^V600E mutation is the most common genetic alteration identified in PTC. There are few data concerning an association between the rising incidence of PTC and the increasing prevalence of BRAF-positive cases. Environmental factors such as iodine intake may be responsible for the changing molecular features of PTC. The aim of this study was to evaluate probable variations in the frequency of the BRAF^V600E mutation in PTC that were diagnosed at a single institution over 14 years in Poland, a country with a demonstrated improvement in iodine supplementation in the early 21st century. Methods: Time-dependent trends in the prevalence of the BRAF^V600E mutation during three time periods (2000–2004, 2005–2009, and 2010–2013) were analyzed. The BRAF mutation was genotyped using direct sequencing, allele-specific polymerase chain reaction (PCR), and real-time PCR in 723 unselected cases of PTC that were diagnosed in 2000–2013. Trends in the clinicopathologic characteristics of all PTCs and BRAF^V600E-positive PTCs were also analyzed. Results: The proportion of PTCs with mutations significantly increased over the study period (54.8% vs. 70.6%; p = 0.001). The median tumor size of all and BRAF-positive tumors decreased (p = 0.008 and p = 0.001, respectively) and correlated with an increase in the proportion of all and mutated microcarcinomas (p = 0.003 and p = 0.003, respectively). A decrease in all and mutated tumors between 2 and 4 cm was also observed (p = 0.002 and p = 0.006, respectively). A significant decrease in tumors ≥4 cm in size was only observed in BRAF-positive cases (p = 0.017). The proportion of classic PTC with BRAF^V600E mutation was observed to increase (57.6% vs. 74.4%; p = 0.001) and was stable for the follicular variant of PTC (p = 0.336). Conclusions: The prevalence of the BRAF^V600Emutation increased significantly in PTCs diagnosed in the authors' institution. Improved detection and several causative factors, most likely environmental and changes in iodine intake, may contribute to the increasing occurrence of TC.

GSTM1, GSTT1, and GSTP1 polymorphisms and colorectal cancer risk in Polish nonsmokers GSTM1, GSTT1, and GSTP1 polymorphisms and colorectal cancer risk in Polish nonsmokers

Immunohistochemistry cannot replace DNA analysis for evaluation of BRAF V600E mutations in papillary thyroid carcinoma Immunohistochemistry cannot replace DNA analysis for evaluation of BRAF V600E mutations in papillary thyroid carcinoma

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. We studied 62 AF patients 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 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. Patients were followed for a mean of 55 months (range, 23 to 64 months). In the thrombocytopenia group bleeding risk was higher (mean HASBLED 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 non-major 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, respectively). The risk of bleeding and stroke was unaffected by the type of the NOAC used in both groups. Major bleedings and CRNMB in thrombocytopenic patients on NOACs were predicted only by age (HR 1.1, 95% CI 1.0-1.3, p=0.04). Our findings indicate that in AF patients with mild thrombocytopenia, anticoagulation with NOAC at reduced doses seems to be safe and effective.