Wartość powtórnego badania stanu mutacji genu BRAF V600E w diagnostyce raka brodawkowatego tarczycy

  Introduction: Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. Material and methods: All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. Results: Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. Conclusions: Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics. (Endokrynol Pol 2016; 67 (1): 35–40)    Wstęp: Choroba guzkowa tarczycy to jedna z najczęściej wykrywanych patologii w populacji osób dorosłych w regionach z deficytem jodu. Około 30% aspiratów tarczycy jest klasyfikowanych jako nie do zdiagnozowania/niesatysfakcjonujące lub nieokreślone. Jednakże, pacjenci z nieokreślonym wynikiem cytologii nadal poddawani są operacjom. Celem niniejszego badania było ustalenie wartości diagnostycznej powtórnego badania mutacji genu BRAF V600E wśród pacjentów z rakiem brodawkowatym tarczycy. Materiał i metody: Wszystkich pacjentów poddano biopsji aspiracyjnej cienkoigłowej guzka tarczycy pod kontrolą USG. Przydzielono ich do jednej z czterech grup (nieokreślona lub dodatnia dla komórek złośliwych) klasyfikacji Bethesda do klasy obrazów cytologicznych. Badanie genetyczne mutacji genu BRAF V600E przeprowadzono dla wszystkich próbek uzyskanych z aspiracyjnej cytologii cienkoigłowej. Wszystkich pacjentów zoperowano. Jednocześnie przeprowadzono badanie histologiczne usuniętych tkanek. Dodatkowa analiza mutacji BRAF V600E z próbki histologicznej została przeprowadzona dla przypadków początkowo BRAF ujemnych. Wyniki: Dwustu czternastu pacjentów poddano badaniu. U 106 pacjentów (49,53%) zdiagnozowano raka tarczycy. Z tychże pacjentów, u 95 (89,62%) zdiagnozowano raka brodawkowatego tarczycy. U 62 pacjentów (65,26%) mutacja BRAF V600E była dodatnia, u 33 (34,74%) histologicznie potwierdzonych przypadków raka brodawkowatego tarczycy była ona ujemna. Po badaniu genetycznym stwierdzono 74 (77,89%) przypadki raka brodawkowatego tarczycy dodatnich dla mutacji BRAF V600E i 21 (22,11%) ujemnych. Wnioski: Powtórne badanie mutacji genu BRAF V600E za pomocą aspiracji cienkoigłowej może potencjalnie przyczynić się do zwiększenia czujności w wykrywaniu raka brodawkowatego tarczycy. (Endokrynol Pol 2016; 67 (1): 35–40)

Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers

Monitoring of T-cell acute lymphoblastic leukemia by flow cytometry

Minimal residual disease (MRD) predicts the outcome of acute lymphoblastic leukemia (ALL). Flow cytometry (FC) is one of the most sensitive and most applicable methods for MRD diagnostics, but there is still no agreement on the “gold standard” of the method. We tried to optimize flow cytometric MRD detection in T-ALL. Fourteen adults and 11 children with T-ALL and 12 normal bone marrow (BM) donors were enrolled in the study. We found that the most common phenotypic aberrations in T-ALL were TdT and CD99 coexpression on T-cells in BM. Therefore for MRD detection we developed a limited four-color marker panel (TdT/CD7/cCD3/CD19 and CD99/CD7/cCD3/CD2) and a standard analysis strategy. This assay was evaluated on BM of healthy controls. Less than 0.01% TdT+ or CD99 bright T-cells were found in normal BM. MRD was detected in 9 adult patients and 1 child at different time-points of treatment. The average TdT and CD99 mean fluorescence intensity (MFI) value of residual blasts fluctuated during therapy, but it still remained higher than MFI of normal T-cells. Our established MRD detection method differentiated leukemic lymphoblasts with sensitivity in the range of 0.01% and did not give any false positive results in normal BM

The COVID-19 pandemic reveals the wide-ranging role of biobanks

The pandemic of COVID-19 reached an unprecedented scale in terms of spread and deaths, its mitigation required a joint effort of governments, hospitals, private companies and other organizations. One type of organization that could undertake a major role in the process is biobank – a mediator between clinical practice and research. Naturally, biobanks are well equipped to alleviate the burden of a pandemic with their expertise in biospecimen and health information collection, sample preparation and storage, bioethics and project management. Here, we present the participation of Vilnius Santaros Klinikos Biobank (BB VSK), Lithuania in the overall management of the pandemics on the national level. We further discuss the role of biobanks in preparation and management of future pandemics

Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis

The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients—during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed

Gilteritinib maintenance after allogeneic stem cell transplantation for FLT3 mutated acute myeloid leukemia

A proportion of FLT3m AML patients remain in prolonged CRs on Gilteritinib maintenance after alloSCT despite prior exposure to Midostaurin, Gilteritinib and Venetoclax. Conversion from positive MRD to negative MRD was confirmed in several cases. Relapses post-Gilteritinib maintenance were enriched with RAS pathway mutations and clinically relevant clonal evolution such as loss of FLT3m or gain of BCR-ABL1. The toxicity of Gilteritinib was manageabl

Therapeutic plasma exchange in multiple sclerosis patients with abolished interferon-beta bioavailability

BACKGROUND Neutralizing antibodies (NAb) to interferon-beta (IFN-β) are associated with reduced bioactivity and efficacy of IFN-β in multiple sclerosis (MS). The myxovirus resistance protein A (MxA) gene expression is one of the most appropriate markers of biological activity of exogenous IFN-β. We hypothesized that therapeutic plasma exchange (TPE) can restore the ability of IFN-β to induce the MxA mRNA expression and that maintenance plasmapheresis can sustain the bioavailability of IFN-β. MATERIAL AND METHODS Eligible patients underwent 4 primary separate plasma exchange sessions. After the induction TPE sessions, they were transferred to maintenance plasmapheresis. Bioactivity of IFN-β was expressed as in vivo MxA mRNA induction in whole blood using RT-qPCR. RESULTS Six patients with low IFN-β bioavailability detected by the MxA mRNA response were included. Four patients became biological responders after induction plasmapheresis. In 2 patients an increase of MxA mRNA expression was found, but the values persisted below the cut-off and the patients remained as "poor biological responders". The effect of maintenance plasmapheresis was transient: MxA mRNA expression values reverted to the baseline levels after 1-2 months. CONCLUSIONS Therapeutic plasma exchange is able to restore the bioavailability of IFN-β in the majority of studied patients, but the effect of TPE on the IFN-β bioavailability was transient