Przydatność określania obecności mutacji BRAF V600E w biopsji aspiracyjnej celowanej cienkoigłowej w zmianach niezdeterminowanych

  Introduction: Fine-needle aspiration biopsy (FNAB) is regarded as the gold standard method for the diagnosis of thyroid nodules, but it has its limitations. Additional methods that would improve sensitivity and specificity in the diagnosis of thyroid cancer (TC), especially in indeterminate lesions. Molecular tests seem to be such a tool. BRAF V600E mutation (the most common in TC) can be detected in FNAB and can be potentially a very useful ancillary marker for FNAB practice. The aim of our study was to evaluate the usefulness of the detection of the BRAF V600E mutation in FNAC in the early diagnosis of TC in patients with indeterminate cytology. Material and method: 2290 FNAB were performed and 147 indeterminate results (group 3, 4, and 5 of the Bethesda system) were obtained. Material from these groups was submitted for molecular tests for the occurrence of BRAF V600E mutation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the tests were calculated. Results: Determining the presence of BRAF V600E mutation in FNAC material in groups 3 and 4 together and in group 5 is associated with sensitivity of TC diagnosis of 37.5% and 81.8%, respectively. In all cases the detection of BRAF V600E mutation was associated with histopathologically proving the presence of TC (specificity of the test — 100%). Conclusions: The presence of BRAF V600E mutation in FNAC material is always associated with the presence of TC. The usefulness of determining the presence of BRAF V600E in FNAC in cytological groups 3 and 4 is associated with low sensitivity in the diagnosis of thyroid cancer. Due to its high specificity BRAF V600E study may be useful in determining the scope of surgery in patients in cytological group 5. (Endokrynol Pol 2016; 67 (1): 41–47)    Wstęp: Biopsja aspiracyjna celowana cienkoigłowa (BACC) jest uznawana za złoty standard w diagnostyce guzków tarczycy. Ma ona jednak swoje ograniczenia. Poszukiwane są więc dodatkowe metody, które poprawiłyby czułość i specyficzność diagnozowania raka tarczycy, zwłaszcza w przypadku zmian niezdeterminowanych w BACC. Badania molekularne wydają się być takim narzędziem. Mutacja BRAF V600E (najczęstsza w raku tarczycy) może być wykrywana w materiale z biopsji i może wspomagać BACC w rozpoznawaniu raka tarczycy. Celem pracy była ocena przydatności wykrywania mutacji BRAF V600E w BACC w zmianach niezdeterminowanych we wczesnej diagnostyce pacjentów ze zmianami ogniskowymi w tarczycy. Materiał i metody: Przeprowadzono 2290 BACC, uzyskując w 147 próbkach wyniki niezdeterminowane (grupy 3, 4 i 5 wg klasyfikacji Bethesda). W grupie tej przeprowadzono badania molekularne w kierunku występowania mutacji BRAF V600E. Obliczono czułość, swoistość, wartość predykcyjną dodatnią, wartość predykcyjną ujemną i dokładność testu. Wyniki: Obecność mutacji BRAF V600E w grupach cytologicznych 3 i 4 łącznie oraz w grupie 5 wiązała się z czułością w rozpoznawaniu raka tarczycy odpowiednio 37,5% i 81,8%. W każdym przypadku wykrycia mutacji BRAF V600E w badaniu pooperacyjnym rozpoznano raka tarczycy (specyficzność testu —100%). Wnioski: Obecność mutacji BRAF V600E w materiale BACC jest zawsze związana z obecnością RT. Przydatność określenia obecności BRAF V600E w BACC w grupach cytologicznych 3 i 4 jest związana z niską czułością rozpoznania RT. Ze względu na wysoką specyficzność BRAF V600E badania mogą być przydatne w określaniu zakresu operacji u pacjentów z grupy cytologicznej 5. (Endokrynol Pol 2016; 67 (1): 41–47)

The influence of the reclassification of NIFTP as an uncertain tumour on risk of malignancy for the diagnostic categories according to the Bethesda system for reporting thyroid cytopathology

Introduction: The noninvasive encapsulated, follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The exclusion of NIFTP from the group of malignant tumours decreases the risk of malignancy (RoM) as defined by the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of the present study was to evaluate the RoM for each category in TBSRTC with and without exclusion of NIFTP from the tally of malignancies. Material and methods: The present study included 998 thyroid nodules cases. All patients underwent diagnostic tests, including fine-needle aspiration cytology, and received surgical treatment. Slides for all resection specimens with a diagnosis of cancer were reviewed to identify NIFTP. The RoM for each of the categories in TBSRTC with and without exclusion of NIFTP from the malignant tumours was evaluated. Results: The RoM decreased with the exclusion of NIFTP from malignant categorisation with the following values for the different TBSRTC categories: non-diagnostic (ND): 0%; benign: 0%; atypia/follicular lesion of undetermined significance (AUS/FLUS): 1.6%; follicular neoplasm/suspicious for follicular neoplasm (FN/SFN): 0.7%; suspicious for malignancy (SUS): 6.9%; and malignant: 2.5%. The difference of 2.5% in the malignant category was statistically significant (p = 0.0253). Conclusions: The RoM for specific TBSRTC categories needs to be defined for each treatment centre because it is important for the selection of the appropriate surgical treatment for thyroid tumours

A critical look at the new possibilities of therapeutic use of statins – a summary of the current state of knowledge

Hypercholesterolemia is a condition characterized by total cholesterol levels exceeding 200 mg/dl. A breakthrough in its treatment was the introduction of the first representative of the status - lovastatin. The mechanism of their action relies on inhibition of the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme responsible for converting HMG-CoA to mevalonic acid, the main substrate in the synthesis of endogenous cholesterol. The progress of experimental and clinical studies on action statins indicates a number of other biological properties of this group of compounds, and thus their pharmacological potential. The possibility of their use in the pharmacotherapy of cardiovascular diseases, hyperandrogenism in women with polycystic ovary syndrome (PCOS), osteoporosis, type 2 diabetes, neurodegenerative diseases, or cancer has been so far highlighted. The aim of this paper was to systematize the knowledge of statin drugs in terms of the progress of studies on their biological activity indicating the possibility of their potential use in the treatment of diseases other than those related to the cardiovascular system, along with verification of their safety profile and demonstrated adverse effects (DN) as a result of their intake. The literature review was conducted by a screening of the following scientific databases - PubMed and Google Scholar (the analysis lasted from March 2022 to February 2023). The keywords used for searching were disease-related and DN-related. Statins have shown potential to alleviate symptoms of androgen excess in women suffering from polycystic ovary syndrome (PCOS). Studies relating to their effect on the treatment of Alzheimer's disease and dementia indicate a reduction in progressive neurodegenerative changes, and thus suggest their potential use in the prevention and treatment of comorbid cardiovascular disease. Moreover, statins tend to reduce morbidity, increase survival, and alleviate the progression of cancer. The results of studies of the effects of these drugs on the possibility or development of Parkinson's disease, osteoporosis and the etiology of muscle symptoms appear to be inconsistent in the relationship of their benefits to DN. Unfortunately, it seems that they have also led to disturbances in carbohydrate metabolism and increased the risk of type II diabetes mellitus (NODM). Studies on the effect of the nocebo effect during statin therapy on the frequency with which patients experience DN have confirmed the presence of this effect. Analysis of the collected studies shows considerable potential for expanding the current therapeutic indications of the drugs in question. However, further randomized controlled trials are required to determine the precise effective dose, duration of therapy for a specific statin

Crystal structure of 2-bromobenzoic acid at 120 K: a redetermination

The crystal structure of the title compound, C7H5BrO2, was originally studied using photographic data at room temperature with Cu Kα radiation [Ferguson & Sim (1962). Acta Cryst. 15, 346–350]. The present study was undertaken at 120 K with a CCD diffractometer using Cu Kα radiation, and resulted in improved geometrical parameters. In the molecule, the carboxy group is inclined to the benzene ring by 18.7 (2)° and there is a close intramolecular Br...O contact of 3.009 (3) Å. In the crystal, molecules are linked by pairs of O—H...O hydrogen bonds, forming inversion dimers with the classical R22(8) ring motif for carboxylic acids. Neighbouring dimers are linked by weak C—H...O hydrogen bonds, forming tapes propagating in [1-10]. Adjacent tapes interact by slipped parallel π–π interactions [inter-centroid distance = 3.991 (2), interplanar distance = 3.509 (2) Å, slippage = 1.900 Å] to form columns approximately along the b-axis direction. Neighbouring columns interact dispersively, forming a three-dimensional framework structure

Physical Activity and Its Determinants among Senior Residents of Podlasie, a Green Region of Poland, Based on the National PolSenior Study

Physical activity is essential at all stages of life, and particularly so in the later years. The main objectives of the present work was to evaluate the physical activity of seniors, aged 65 years and older, living in the area of the Podlaskie voivodeship (Podlasie), Poland, based on the results of the nationwide PolSenior project, and to formulate recommendations for health policies implemented by both national and local government units. The study was performed as part of the national PolSenior project, whose aim was to evaluate various aspects of aging in Poland. The physical activity of a group of 186 randomly-selected people aged 65 years and above, 94 men and 92 women, was evaluated by questionnaire. The analysis included participants who took part in physical activity at least several times a week. Although all participants reported a decline in physical activity with age, the men remained physically active for longer. Among the respondents, 68.3% of women and 62.7% of men took short walks around the house as the main form of exercise, with working on the allotment or garden being another frequent activity; however, this was more common among men (53.9%) than women (34.7%). In addition, men were nearly twice as likely to take part in cycling (31.5%) than women (13.1%). The greatest motivation for physical activity given by the respondents was health, as noted by 73.8% of the men and 77.7% of the women. The physical activity of seniors in Podlasie is unsatisfactory and does not fulfil the WHO recommendations regarding the prophylaxis and prevention of chronic illness. This level does not, however, significantly differ from that reported in the nationwide PolSenior study or in other European countries in the Eurobarometer study. The decline in physical activity with age highlights the need for its greater promotion among seniors by local authorities. Such initiatives will help maintain the physical fitness and independence of this age group and contribute to a greater quality of life

Relationship between the Expression of CHK2 and p53 in Tumor Tissue and the Course of Papillary Thyroid Cancer in Patients with <i>CHEK2</i> Germline Mutations

The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2