scholarly journals Phenotypic heterogeneity and diagnostic features of transthyretin amyloidosis with polyneuropathy

2021 ◽  
Vol 11 (3) ◽  
pp. 12-36
Author(s):  
S. S. Nikitin ◽  
S. N. Bardakov ◽  
N. A. Suponeva ◽  
I. V. Zhirov ◽  
T. A. Adyan ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Diagnostic Algorithm ◽  
Diagnostic Features ◽  
International Consensus ◽  
Transthyretin Amyloidosis ◽  
Genetic Characteristics ◽  
Attr Amyloidosis ◽  
Initial Symptoms ◽  
The Russian Federation

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic progressive fatal disease, for which a modifying therapy has recently been proposed that delays the progression of the disease and improves the patient’s quality of life. The delay in the diagnosis of ATTR-amyloidosis is associated with the heterogeneity of the manifestations of the disease, as well as insufficient awareness of doctors of different specialties about the disease. A review of recent studies on the symptomatology, diagnosis, molecular genetic characteristics of ATTR-amyloidosis and the most common forms of the disease with the predominant involvement of peripheral nerves and the heart, as well as the kidneys, gastrointestinal tract, and eyes is presented. The international consensus recommendations for the diagnosis of suspected ATTR-amyloidosis using modern methods that facilitate early and accurate diagnosis are discussed. The reasons and the most frequent misdiagnoses of ATTR-amyloidosis, which also lead to a delay in the timely appointment of therapy, are considered. Molecular genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy and cardiomyopathy. A diagnostic algorithm based on the initial symptoms and manifestations of the cardiovascular and nervous systems facilitates the identification of a patient with clinical suspicion of ATTR-amyloidosis by the general practitioner. Early diagnosis is critically important for patients with ATTR polyneuropathy, since the early prescription of Vindakel (tafamidis), registered in the Russian Federation in 2017, allows a significant clinical effect to be obtained. Timely administration of Vindakel significantly slows down the progression of the disease, improves the prognosis and quali  ty of life in patients with ATTR polyneuropathy.

scholarly journals Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Morie Gertz ◽  
David Adams ◽  
Yukio Ando ◽  
João Melo Beirão ◽  
Sabahat Bokhari ◽  
...  
Keyword(s):  
General Practitioner ◽  
Working Group ◽  
Medical Center ◽  
Diagnostic Algorithm ◽  
Accurate Diagnosis ◽  
Consensus Recommendation ◽  
Transthyretin Amyloidosis ◽  
Attr Amyloidosis ◽  
Consensus Recommendations ◽  
Initial Symptoms

Abstract Background Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. Methods These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. Results The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. Conclusions A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.

scholarly journals Monogenic auto-inflammatory diseases in children and adults: what a rheumatologist should know

2019 ◽  
Vol 57 (2) ◽  
pp. 125-132 ◽  
Author(s):  
S. O. Salugina ◽  
E. S. Fedorov ◽  
E. M. Agafonova
Keyword(s):  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Molecular Genetic ◽  
Disease Onset ◽  
Organ Damage ◽  
Genetic Characteristics ◽  
Current State ◽  
Principles Of Treatment ◽  
Satisfactory Quality

The article presents information on the current state of the problem of autoinflammatory diseases (AID) in rheumatology, reflects the clinical and demographic, laboratory and molecular genetic characteristics of the main monogenic AID (mAID), the most common in real clinical practice. Approaches to the diagnosis and differential diagnosis of these conditions are presented. The variants of classification and diagnostic criteria of the most studied mAID are discussed. The principles of treatment with an emphasis on the use of targeted therapy with interleukin 1 (IL1) inhibitors are shown. The clinical examples demonstrate the variants of late diagnosis of the mAID in adult patients with the disease onset in childhood. Different variants of multi-organ damage are considered. Effectiveness of therapy with IL1β inhibitor kanakinumab is demonstrated. Even in such cases it provided the possibility of significant symptoms regression and restoration of a satisfactory quality of life.

scholarly journals Clinical and molecular genetic characteristics of MODY1—3 cases in the Russian Federation as shown by NGS

2018 ◽  
Vol 63 (6) ◽  
pp. 369-378
Author(s):  
Natalya A. Zubkova ◽  
Olesya A. Gioeva ◽  
Yulia V. Tikhonovich ◽  
Vasily M. Petrov ◽  
Evgeny V. Vasilyev ◽  
...  
Keyword(s):  
Russian Federation ◽  
Clinical Presentation ◽  
Molecular Genetic ◽  
Inclusion Criteria ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Synonymous Mutations ◽  
Endogenous Insulin ◽  
Hnf1a Gene ◽  
The Russian Federation

Objective — the research was aimed at studying clinical and molecular genetic characteristics of the most common subtypes of MODY (1—3) detected by NGS. Material and methods. The study included 312 patients (162 boys and 150 girls) aged 3 months to 25 years with suspected MODY. Inclusion criteria were as follows: carbohydrate metabolism disorders of varying severity, negative titer of ICA, IA2, and GAD autoantibodies, preserved secretion of endogenous insulin. NGS technique was used for molecular genetic studies. Custom DNA Panel was used for the multiplex PCR and sequencing using the Ion Ampliseq technique. Custom Diabetes Panel included 28 genes (13 MODY candidates genes and other diabetes-associated genes). Non-synonymous mutations that were not previously described were rated as «probably pathogenic» if they had minor allele frequency of <0.1% and «pathogenic» when assessed against the ANNOVAR database. Results. Mutations in MODY candidate genes were detected in 178 (57.1%) probands. Of these, 99 mutations in GCK99 gene were found in 129 (41.4%) probands and 77 relatives, 20 mutations in HNF1A gene were found in 19 (6.1%) probands and 14 relatives, 8 mutations in HNF4A gene — in 9 (2.9%) probands and 3 relatives. All detected mutations were heterozygous. MODY1 subtype was not previously described in the Russian Federation. Conclusions. The Russian population is dominated by MODY2 subtype. Only MODY2 is characterized by typical clinical presentation. NGS is a highly effective method in the diagnosis of MODY.

Iatrogenic hepatic damage as a problem of modern surgery (literature review)

2021 ◽  
Vol 22 (3) ◽  
pp. 94-101
Author(s):  
Ya. A. Chakhchakhov ◽  
◽  
B. K. Gibert ◽  
◽  
Keyword(s):  
Quality Of Life ◽  
Surgical Treatment ◽  
Bile Ducts ◽  
Diagnostic Algorithm ◽  
Controversial Issues ◽  
Surgical Interventions ◽  
Iatrogenic Damage ◽  
Extrahepatic Bile Ducts ◽  
The Russian Federation

Iatrogenic damage to the extrahepatic bile ducts occurs in a fairly large number of observations, despite constant work aimed at improving surgical interventions. The most optimal chosen therapeutic tactics, as well as the timing of the revealed damage to the bile ducts, determine the effectiveness and quality of care provided to this category of patients. We also have to state that, to date, in the Russian Federation there is no unambiguously generally accepted and approved therapeutic and diagnostic algorithm for iatrogenic damage to the extrahepatic bile ducts. One of the main aspects of the effectiveness of the applied treatment tactics is the level of quality of life of patients who underwent surgical treatment. Treatment and management of patients with iatrogenic damage to the extrahepatic bile ducts still have a fairly large number of controversial issues, the solution of which should improve the immediate results of surgical treatment of this category of patients.

scholarly journals Molecular, biological and diagnostic features of Ewing sarcoma and undifferentiated small round cell sarcomas of bone and soft tissue

2021 ◽  
Vol 13 (1) ◽  
pp. 24-31
Author(s):  
K. Y. Sinichenkova ◽  
V. Y. Roschin ◽  
A. E. Druy
Keyword(s):  
Soft Tissue ◽  
Gene Rearrangement ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Molecular Genetic ◽  
Round Cell ◽  
Diagnostic Features ◽  
Genetic Characteristics ◽  
Small Round Cell ◽  
Ets Family

Ewing’s sarcoma is a highly malignant small round cell tumor with a unique rearrangement of the EWSR1 (FUS) gene with partners genes of ETS family. Tumors with Ewing's sarcoma morphological features lacking without specific EWSR1 rear-rangement called undifferentiated small round cell sarcomas of bone and soft tissue. This group includes: sarcomas with СIC gene rearrangement, sarcomas with BCOR gene rearrangement and sarcomas with EWSR1 (FUS) gene rearrangement with non-ETS gene-partner. Clinical, morphological and molecular genetic characteristics of these groups of tumors will be described below

Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

Risks and economic security of the life support system of citizens in the field of housing and communal services

2020 ◽  
Vol 19 (3) ◽  
pp. 175-191
Author(s):  
Vladimir M. Yakovlev
Keyword(s):  
Quality Of Life ◽  
Russian Federation ◽  
Support System ◽  
Internal Control ◽  
Life Support ◽  
Economic Security ◽  
Security System ◽  
Life Support System ◽  
The Russian Federation

The article analyzes the problems of the manifestation of risks of shadow and criminal activity in the life support system of citizens of the Russian Federation, the dissemination of which requires the development of effective measures to prevent and eliminate them. The most important issue is the formation of an effective economic security system with an emphasis on the new quality of life support for citizens of the Russian Federation in an adequate combination with the high growth rate of NTP in the Russian economy. The new technological structure emerging from the new achievements of scientific and technological progress involves the harmonization of the pace of scientific and technological development, combined with an adequate improvement in the quality of life support for citizens performing such achievements. Owing to this fact formation of new quality of the housing and communal services (HCS) as bases of life support of citizens becomes a prerequisite of increase in performance and intellectualization of human work. With this in mind, early recognition, prevention and elimination of risks of shadow and criminal activities in the housing and communal services system (housing and communal services) is considered as a significant mechanism to increase the effectiveness of the system of comfortable life support for citizens of the Russian Federation. The existing lag in the development of a high-quality and comfortable system for providing citizens of Russia on the basis of housing and communal services, the subject of which is the provision of quality and comfortable services, influenced by numerous risks of shadow and criminal influence, becomes a condition for intensifying economic development and increasing labor productivity on this basis. The need to develop and use modern scientific and technical achievements, especially in the field of digitalization, is emphasized in order to increase the efficiency of the economic security system of housing and communal services organizations based on innovative control mechanisms - internal control, audit, compliance control, taking into account financial investigations in order to prevent and eliminate the risks of shadow and criminal activities in the housing and communal services system.

Assessing the quality of public health in the Russian Federation and Israel: Main problems and solutions

2020 ◽  
Vol 19 (4) ◽  
pp. 618-632
Author(s):  
A.S. Panchenko
Keyword(s):  
Public Health ◽  
Russian Federation ◽  
Population Based ◽  
The Public ◽  
Disability Adjusted Life ◽  
Problems And Solutions ◽  
The Russian Federation ◽  
Disability Adjusted Life Year ◽  
Practical Recommendations

Subject. The article addresses the public health in the Russian Federation and Israel. Objectives. The focus is on researching the state of public health in Russia and Israel, using the Global Burden of Disease (GBD) project methodology, identifying problem areas and searching for possible ways to improve the quality of health of the Russian population based on the experience of Israel. Methods. The study draws on the ideology of the GBD project, which is based on the Disability-Adjusted Life-Year (DALY) metric. Results. The paper reveals the main causes of DALY losses and important risk factors for cancer for Russia and Israel. The findings show that the total DALY losses for Russia exceed Israeli values. The same is true for cancer diseases. Conclusions. Activities in Israel aimed at improving the quality of public health, the effectiveness of which has been proven, can serve as practical recommendations for Russia. The method of analysis, using the ideology of the GBD project, can be used as a tool for quantitative and comparative assessment of the public health.

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