PREDICTIVE VALUE OF THE DYNAMIC DETERMINATION OF CIRCULATING TUMOR DNA ON PFS IN PATIENTS WITH EGFR MUTATED NSCLC, WITH OSIMERTINIB THERAPY

2020 ◽  
Vol 66 (2) ◽  
pp. 135-142
Author(s):  
Fedor Moiseenko ◽  
Mariya Stepanova ◽  
Nikita Volkov ◽  
Albina Zhabina ◽  
A. Myslik ◽  
...  
Keyword(s):  
Predictive Value ◽  
Molecular Genetic ◽  
Predictive Marker ◽  
Circulating Tumor Dna ◽  
Qualitative Assessment ◽  
Genetic Profile ◽  
T790m Mutation ◽  
Rare Mutations ◽  
Effect Of Therapy ◽  
Pcr Method

Aim: study of the predictive value of determining ctDNA during treatment with osimertinib in patients with NSCLC with EGFR mutation. Methods: The study included patients with metastatic EG-FR-associated NSCLC, in whom, with progression against the background of 1st - 2nd generation TKIs, the T790M mutation was detected. Patients received osimertinib therapy 80 mg/ day, daily, until progression. Before treatment, and then every 2 months, whole blood was taken to conduct a qualitative assessment of ctDNA in dynamics by the RT-PCR method. Results: From 2016 to 2019 in St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncology), 22 patients were identified T790M associated progression of EGFR NSCLC. 81.9% (18/22) are women, 18.1% (4/22) are men. The average age is 61.2 years (50-75). 1/22 had smoking experience for more than 30 years. The molecular genetic profile in 16 is represented by ex19del, 5 L858R, 1 -a combination of rare mutations G719S+S768I. The effect of therapy was evaluated in 20/22 patients. PR and SD were registered in 9/20 (45%) and 10/20 (50%) patients, respectively. Median PFS - 16.7 months (cI 95%, 11,4-22,0). In 12/22 patients was observed the disappearance of ctDNA T790M after 2 months of osimertinib therapy. PFS is 18,9 months (95% CI, 14,8-19,7), in patients with no mutation detected in the second month of treatment compared with the group of patients in which the ctDNA was determined (PFS 8.0 months) (CI 95%, 4,2-11,8) (p=0.015). Correlation analysis did not reveal any clinical factors associated with the disappearance of ctDNA. Conclusions: The disappearance of ctDNA in plasma after 2 months of treatment with osimertinib is associated with an increase in PFS and can be considered as a predictive marker in patients with metastatic NSCLC EGFR T790M.

scholarly journals Neopterin predicts disease severity in hospitalized patients with COVID-19

2020 ◽  
Author(s):  
Rosa Bellmann-Weiler ◽  
Lukas Lanser ◽  
Francesco Burkert ◽  
Stefanie Seiwald ◽  
Gernot Fritsche ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Retrospective Analysis ◽  
Disease Severity ◽  
Predictive Value ◽  
Clinical Management ◽  
Inflammatory Markers ◽  
Predictive Marker ◽  
Hospitalized Patients ◽  
Icu Admission ◽  
Circulating Inflammatory Markers

Abstract This study evaluates the predictive value of circulating inflammatory markers, especially neopterin, in patients with COVID-19. Within this retrospective analysis of 115 hospitalized COVID-19 patients, elevated neopterin levels upon admission were significantly associated with disease severity, risk for ICU admission, need for mechanical ventilation and death. Therefore, neopterin is a reliable predictive marker in patients with COVID-19 and may help to improve the clinical management of patients.

scholarly journals Diagnostic accuracy of droplet digital PCR for detection of EGFR T790M mutation in circulating tumor DNA

2018 ◽  
Vol Volume 10 ◽  
pp. 1209-1218 ◽  
Author(s):  
Rui Zhang ◽  
Bojiang Chen ◽  
Xiang Tong ◽  
Ye Wang ◽  
Chengdi Wang ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Droplet Digital Pcr ◽  
T790m Mutation ◽  
Tumor Dna ◽  
Egfr T790m

scholarly journals Residual Vein Thrombosis Echogenicity Is Associated to the Risk of DVT Recurrence: A Cohort Study

2017 ◽  
Vol 24 (3) ◽  
pp. 477-482 ◽  
Author(s):  
Bruna M. Mazetto ◽  
Fernanda L. A. Orsi ◽  
Sandra A. F. Silveira ◽  
Luis F. Bittar ◽  
Mariane M. C. Flores-Nascimento ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Late Complication ◽  
Predictive Marker ◽  
Predictive Markers ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer

Although deep vein thrombosis (DVT) recurrence is a common late complication of the disease, there are few predictive markers to risk-stratify patients long-term after the thrombotic event. The accuracy of residual vein thrombosis (RVT) in this context is controversial, possibly due to a lack of a standardized methodology. The objective of the study was to evaluate the accuracy of RVT echogenicity as a predictive marker of late DVT recurrence. To evaluate the accuracy of RVT echogenicity as a predictive marker of late DVT recurrence. This prospective study included patients with history of DVT in the past 33 months. Ultrasound examination was performed to detect the presence of RVT, and its echogenicity was determined by calculating the grayscale median (GSM) of the images. Blood samplings were taken for plasma D-dimer levels. Patients were followed-up for 28 months and the primary end point was DVT recurrence. Deep vein thrombosis recurrence was confirmed or excluded by ultrasound during the follow-up. Fifty-six patients were included, of which 10 presented DVT recurrence during the follow-up. D-dimer levels above 630 ng/mL conferred higher risk for recurrence with a negative predictive value of 94%. The absence of RVT was a protective marker for recurrence with a negative predictive value of 100%. Also, the presence of hypoechoic RVT, determined by GSM values below 24, positively predicted 75% of DVT recurrences. Our results suggest that the persistence of RVT and, particularly, the presence of hypoechoic thrombi (GSM < 24) are predictive markers of the risk of DVT recurrence. Residual vein thrombosis echogenicity, by GSM analysis, could represent a new strategy for the evaluation of recurrence risk in patients with DVT.

The molecular genetic profile of neuroblastoma

2014 ◽  
Vol 20 (2) ◽  
pp. 76-83 ◽  
Author(s):  
Paul Scott Thorner
Keyword(s):  
Molecular Genetic ◽  
Genetic Profile

scholarly journals ETIOTROPIC THERAPY FOR DIFFERENT FORMS OF HEPATITIS B

2021 ◽  
Vol 5 (1) ◽  
pp. 50-55
Author(s):  
E. N. Priima ◽  
◽  
A. D. Bushmanova ◽  
K. E. Novak ◽  
E. V. Esaulenko ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Clinical Laboratory ◽  
Molecular Genetic ◽  
Genetic Profile ◽  
B Virus ◽  
Hbsag Seroconversion

Background. Currently, etiotropic therapy of hepatitis B in most cases is carried out using nucleot(s)ide analogues. The ultimate goal of the therapy depends on the period of its administration – in acute or chronic hepatitis. The influence of the molecular genetic profile of the hepatitis B virus on the effectiveness of therapy in both acute and chronic forms of the disease has not yet been established, which requires further research. Objective. To assess the possibilities of modern etiotropic therapy in acute and chronic forms of hepatitis B. Material and methods. The article analyzes the indicators of clinical, laboratory and instrumental data of patients who received etiotropic therapy with nucleot(s)ide analogues. Results. Etiotropic therapy resulted in a viral load decrease to an undetectable level in all patients regardless of the course of hepatitis B and infection with either a "mutant" or "wild" virus strain. In acute hepatitis B, HBV DNA was not detected in 100% of cases after 24 weeks of therapy, in HBsAg seroconversion - after 36 weeks; in chronic hepatitis B - after 36 weeks without HBsAg seroconversion. Six months after the completion of the treatment, the patients with chronic hepatitis B developed relapse in 89.7% of cases, but the viral load was less than 2000 IU / ml, and the severity of liver fibrosis was insignificant. In the rest of the cases, resumption of therapy was required. Conclusions. It was found that mutations of the hepatitis B virus do not affect the effectiveness of etiotropic therapy. The rate of viral load decrease correlates with the form of hepatitis B and is significantly higher in acute disease.

scholarly journals Prognostic Value of Coronary Artery Calcium Score in Hospitalized COVID-19 Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Maria-Luiza Luchian ◽  
Stijn Lochy ◽  
Andreea Motoc ◽  
Dries Belsack ◽  
Julien Magne ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery ◽  
Negative Predictive Value ◽  
Coronary Artery Calcium ◽  
Predictive Value ◽  
Qualitative Assessment ◽  
Hospital Treatment ◽  
Major Adverse Cardiovascular Events ◽  
Imaging Data ◽  
Laboratory Findings

Background: The association of known cardiovascular risk factors with poor prognosis of coronavirus disease 2019 (COVID-19) has been recently emphasized. Coronary artery calcium (CAC) score is considered a risk modifier in the primary prevention of cardiovascular disease. We hypothesized that the absence of CAC might have an additional predictive value for an improved cardiovascular outcome of hospitalized COVID-19 patients.Materials and methods: We prospectively included 310 consecutive hospitalized patients with COVID-19. Thirty patients with history of coronary artery disease were excluded. Chest computed tomography (CT) was performed in all patients. Demographics, medical history, clinical characteristics, laboratory findings, imaging data, in-hospital treatment, and outcomes were retrospectively analyzed. A composite endpoint of major adverse cardiovascular events (MACE) was defined.Results: Two hundred eighty patients (63.2 ± 16.7 years old, 57.5% male) were included in the analysis. 46.7% patients had a CAC score of 0. MACE rate was 21.8% (61 patients). The absence of CAC was inversely associated with MACE (OR 0.209, 95% CI 0.052–0.833, p = 0.027), with a negative predictive value of 84.5%.Conclusion: The absence of CAC had a high negative predictive value for MACE in patients hospitalized with COVID-19, even in the presence of cardiac risk factors. A semi-qualitative assessment of CAC is a simple, reproducible, and non-invasive measure that may be useful to identify COVID-19 patients at a low risk for developing cardiovascular complications.

scholarly journals Molecular and biological characteristics of keratin intermediate filaments in intact skin under systemic inflammation

2020 ◽  
pp. 34-39
Author(s):  
Г.А. Демяшкин ◽  
Е.Ю. Шаповалова ◽  
М.Ю. Маланичев ◽  
Д.А. Погосян ◽  
М.А. Батов ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Molecular Genetic ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Critical Conditions ◽  
Genetic Profile ◽  
Intact Skin ◽  
Keratinocyte Proliferation ◽  
Expression Of Genes ◽  
And Migration

Введение. Несмотря на определенный прогресс в изучении патоморфологических механизмов сепсиса и усовершенствовании методов терапии критических состояний, летальность при сепсисе сохраняется на высоком уровне. При тяжелом системном воспалении нарушается морфофункциональное состояние кожного покрова, однако обусловливающие этот эффект механизмы описаны поверхностно. Нуждается в уточнении роль изменения экспрессии генов кератиноцитов цитоскелета, приводящая к нарушению их дифференцировки и миграции на фоне действия эндогенного фактора, индуцированного тяжелым системным воспалением. Цель работы - оценка молекулярно-генетического профиля дифференцировки и миграции кератиноцитов на фоне системного воспаления. Методика. Фрагменты интактной кожи пациентов с подтвержденным сепсисом (n=46) были изучены методом полимеразной цепной реакции в режиме реального времени для определения экспрессии генов промежуточных филаментов кератиноцитов KRT1, KRT10, KRT5, KRT14 и KRT16. Результаты. У пациентов в условии системного воспаления относительная экспрессия KRT1, KRT10, KRT5, KRT14 и KRT16 в интактной коже снижена, несмотря на сохранение уровня экспрессии генов, продукты которых поддерживают агрегацию филаментов и стабильность цитоскелета - FLG, IVL. Заключение. В интактной коже на фоне системного воспаления в отсутствие внешнего повреждающего фактора отмечается разобщение дифференцировки и пролиферации кератиноцитов, способное привести к нарушению барьерной функции кожи. Introduction. Despite some progress in studying pathomorphological mechanisms of sepsis and improvement of therapy for critical conditions, mortality in sepsis remains high. In severe systemic inflammation, the morpho-functional state of skin is compromised; however, the mechanisms responsible for this effect are not completely understood. The role of mutations in keratinocyte cytoskeletal genes leading to disorders of keratinocyte differentiation and migration under the action of an endogenous factor induced by severe systemic inflammation, needs to be clarified. The aim of this work was to assess the molecular genetic profile of keratinocyte differentiation and migration under systemic inflammation. Methods. Fragments of intact skin from patients with confirmed sepsis (n=46) were studied with real-time polymerase chain reaction to determine the expression of keratin intermediate filament KRT1, KRT10, KRT5, KRT14, and KRT16 genes. Results. In patients with systemic inflammation, the relative expression of KRT1, KRT10, KRT5, KRT14, and KRT16 in intact skin was reduced, despite the normal expression of genes whose products support filament aggregation and cytoskeletal stability (FLG and IVL). Conclusion. In the intact skin under systemic inflammation in the absence of an external damaging factor, uncoupling of the keratinocyte differentiation from the keratinocyte proliferation was observed, which may lead to dysfunction of the skin barrier.

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