Early Diagnostics Research Articles

Early diagnostics of motor disorders in children: an interdisciplinary approach

Assessment of motor development is an important part of the study of the neuropsychic development of children, which is carried out by a pediatrician during preventive examinations. To identify the causes of motor disorders, in addition to studying the anamnesis, it is necessary to conduct a physical examination of the child with the appointment of additional research methods. It is important to remember that developmental delay does not always indicate the presence of any disease but requires dynamic monitoring. However, if they progress, then these patients are more likely to be diagnosed with specific neuromuscular disorders. In this case, the pediatrician should pay attention to the neurological status of the child, assess visual acuity and hearing. At the same time, one should not forget that motor disorders are often combined with a general developmental delay (mental retardation) of the child. Fasciculation of the tongue, loss of motor skills, organomegaly, coarsening of facial features, increased levels of creatine phosphokinase (more than 3 times higher than normal), respiratory failure, in the presence of general weakness, a sharp deterioration in the child’s condition, accompanied by lethargy, vomiting, development of convulsive syndrome, disorders detected on MRI of the brain, are alarming symptoms that require urgent intervention by specialists (neurologist, genetics). Also, some hereditary (chromosomal and monogenic) diseases are often combined with the development of motor disorders. The best results are achieved if the early diagnosis of diseases accompanied by movement disorders is carried out using an interdisciplinary approach.

Hybrid CNN and XGBoost Model Tuned by Modified Arithmetic Optimization Algorithm for COVID-19 Early Diagnostics from X-ray Images

Developing countries have had numerous obstacles in diagnosing the COVID-19 worldwide pandemic since its emergence. One of the most important ways to control the spread of this disease begins with early detection, which allows that isolation and treatment could perhaps be started. According to recent results, chest X-ray scans provide important information about the onset of the infection, and this information may be evaluated so that diagnosis and treatment can begin sooner. This is where artificial intelligence collides with skilled clinicians’ diagnostic abilities. The suggested study’s goal is to make a contribution to battling the worldwide epidemic by using a simple convolutional neural network (CNN) model to construct an automated image analysis framework for recognizing COVID-19 afflicted chest X-ray data. To improve classification accuracy, fully connected layers of simple CNN were replaced by the efficient extreme gradient boosting (XGBoost) classifier, which is used to categorize extracted features by the convolutional layers. Additionally, a hybrid version of the arithmetic optimization algorithm (AOA), which is also developed to facilitate proposed research, is used to tune XGBoost hyperparameters for COVID-19 chest X-ray images. Reported experimental data showed that this approach outperforms other state-of-the-art methods, including other cutting-edge metaheuristics algorithms, that were tested in the same framework. For validation purposes, a balanced X-ray images dataset with 12,000 observations, belonging to normal, COVID-19 and viral pneumonia classes, was used. The proposed method, where XGBoost was tuned by introduced hybrid AOA, showed superior performance, achieving a classification accuracy of approximately 99.39% and weighted average precision, recall and F1-score of 0.993889, 0.993887 and 0.993887, respectively.

Early diagnosis and surgical treatment of craniosynostoses

Craniosynostosis is a craniofacial anomaly, characterized by premature fusion of one or more of the cranial sutures. Each suture and their combination correspond to a special type of deformation.Purpose. The study aimed at indicating the difficulties of early diagnostics of various forms of the craniosynostosis and evaluating the quality of treatment of patients with this disease depending on their age.Material and methods. A survey of parents with craniosynostosis who were treated at the Almazov National Medical Research Centre in 2018–2019 was conducted. The parents of 107 patients were surveyed. The main objectives of our research were: to evaluate the timeliness of diagnosis of craniosynostosis at primary health care at patient’s place of residence; to compare the methods of diagnosis verification and to present the results of the parents’ subjective assessment of the results of surgical treatment at the early and long-term postoperative period.Results. The median age of children when they were diagnosed with craniosystosis was 5 months, the median age of patients when they underwent a surgical treatment was 16 months. The median duration of the catamnesis was 6 months. We revealed that the preliminary diagnosis was established by a neurologist and pediatrician only in 21% of cases. Only at 28% of cases, children were directed to neurosurgeon, who confirm the diagnosis. In 38 (35.3%) cases, patient’s parents independently sought medical advice. The diagnosis was verified by the results of the computer tomography in 55% of patients. on because primary care specialists due to the lack of primary care specialists’ awareness about the diagnosis of craniosynostoses and attempts at long-term monitoring and conservative treatment. The timeliness of detection of craniosynostosis in the newborn period and in the|first month of life can significantly improve the cosmetic and functional outcomes of the disease.

Physicochemical and antigenic properties of the urea-extracted surface structures of <i>Yersinia pseudotuberculosis</i> O:1b

Immuno-serological diagnostic tools particularly identifying pathogen antigens are the most important methods of pseudotuberculosis studies. The main immunodominant and species-specific antigens located in the surface structures of the bacterial cell are of practical interest. Thereby the aim of the work was to isolate and characterize biologically active surface structures of the pseudotuberculosis microbe. Here, the living cells of Y. pseudotuberculosis 3704 (O:1b) were lysed by using 9 M urea solution to extract antigens localized in the microbial surface structures. The subcellular fractions obtained such as outer membranes (OM), urea extract (UE) and isolated protein-lipopolysaccharide complex (PLPSC) are characterized by physical and chemical parameters. The protein content in the preparations ranged from 42% to 53%. The polypeptide band of the OM preparation, UE polypeptide and PLPSC for pseudotuberculosis microbe was presented by 14, 16 and 9 major polypeptides with molecular weight ranging from 13.9 kDa to 131.5 kDa, 13.5 kDa to 101.6 kDa, and 20.7 kDa to 66.6 kDa, respectively. Proteolytically active proteins and polypeptides were detected in isolated subcellular fractions (OM and UE) by using the radial enzyme diffusion test and substrate-gel electrophoresis found to be presented by 4 and 7 polypeptides with molecular weight ranging from 28.0 kDa to 118.0 kDa and 29.2 kDa to 97.7 kDa in the OM and UE preparation, respectively. The subcellular fractions obtained are capable to exhibit immunogenic activity after inoculation to experimental animals and antigenic activity while interacting with specific antibodies in the radial immunodiffusion (RID) assay and antibodies labeled with colloidal silver nanoparticles in dot immunoassay (DIA). OM and PLPSC preparations in DIA with immunoglobulins isolated from experimental antisera and labeled with colloidal silver nanoparticles were detected at a concentration of 0.12 g/ml (dry weight), cells of strain Y. pseudotuberculosis 3704 at a concentration of 3, 9 106 m.c./ml, which is similar to the results of DIA with immunoglobulins isolated from commercial pseudotuberculosis antiserum (St. Petersburg) and labeled with nanoparticles of colloidal silver. Thus, the subcellular fractions of pseudotuberculosis microbe isolated by using urea as a lysing and decontaminating agent retain their antigenic and immunogenic properties and enzymatic activity suggesting about their potential benefits for use to improve early diagnostics of pseudotuberculosis.

Features of the cytokine profile in adolescents with microvascular complications of type 1 diabetes mellitus

Despite advances of modern medical science, the consequences associated with management of complications in type 1 diabetes mellitus (DM1) in children and adolescents represent a serious problem. Common development of microvascular diabetic complications (retinopathy, neuropathy, kidney damage) still remains a sufficient obstacle for achieving high quality of life and social adaptation in the young patients, thus promoting studies of immune mechanisms involved in genesis of microvasculature damage under the conditions of dysmetabolic abnormalities associated with DM1. Our goal was to assess the role of altered cytokine balance in blood serum in development of microangiopathies in adolescents with DM1.140 adolescent patients with type 1 diabetes aged 14-18 years were examined being divided in 2 groups: group I included the patients with glycated hemoglobin (HbA1c) level of > 9.0% (n = 65), and group II which included adolescents with HbA1C level of ≤ 9.0% (n = 75). Each group was divided into subgroups: Ia (n = 50) and IIa (n = 38) included adolescents with diabetic retinopathy, nephropathy or neuropathy, whereas groups Ib (n = 15) and IIb (n = 37) were without microvascular complications. The control group consisted of 36 adolescents with normal body weight, without carbohydrate metabolic disorders, and family history of diabetes mellitus. Determination of TNFα, IL-1β, VCAM-1, fractalkine levels in blood serum was performed by enzyme immunoassay using test systems “RayBiotech” (USA), “BIOSCIENCE” (USA).Development of microangiopathies in adolescents with different glycemic control is associated with increased serum concentration of the factors involved in neoangiogenesis and vascular wall remodeling, i.e., TNFα, IL-1β, VCAM-1, compared with control group (p < 0.05), and a statistically significant decrease in fractalkine level in adolescent patients with either complicated, or uncomplicated DM1. The study allowed us to suggest that occurrence of microvascular complications in adolescents with DM1 is associated with impaired immune response tending for altered cytokine balance towards Th1 type, enhanced intercellular interactions, imbalance of bioregulatory molecules, contributing to development of inflammatory immunoregulatory state. The revealed patterns of laboratory markers, along with assessment of metabolic indices, will enable personalized approaches to early diagnostics of microvascular complications in adolescents with DM1 and prevent their further progression.

Prediagnostic biomarkers for early detection of glioma-using case-control studies from cohorts as study approach.

Understanding the trajectory and development of disease is important and the knowledge can be used to find novel targets for therapy and new diagnostic tools for early diagnosis. Large cohorts from different parts of the world are unique assets for research as they have systematically collected plasma and DNA over long-time periods in healthy individuals, sometimes even with repeated samples. Over time, the population in the cohort are diagnosed with many different diseases, including brain tumors. Recent studies have detected genetic variants that are associated with increased risk of glioblastoma and lower grade gliomas specifically. The impact for genetic markers to predict disease in a healthy population has been deemed low, and a relevant question is if the genetic variants for glioma are associated with risk of disease or partly consist of genes associated to survival. Both metabolite and protein spectra are currently being explored for early detection of cancer. We here present a focused review of studies of genetic variants, metabolomics, and proteomics studied in prediagnostic glioma samples and discuss their potential in early diagnostics.

Chronic lymphoproliferative diseases and cardiovascular risk (a literature review)

Heart dysfunction that occurred after using of anticancer drugs and monoclonal antibodies may be a limit factor in treatment of chronic lymphoproliferative diseases (CLPD). Cancer therapy-related cardiovascular toxicity include hypotension, hypertension, arrhythmias, conduction disturbances, pericarditis, thromboembolic events, heart failure, death. The risk of cardiotoxicity may be increased by some factors that include drug exposure, age, history of heart diseases, arterial hypertension, drug combination, previous radiotherapy or chemotherapy. The aim of the work is to assess the impact of anticancer treatment on the occurrence of cardiovascular events in patients with CLPD according to the world scientific literature data. It is important to detect the cardiovascular toxicity before the development of clinical manifestations of damage to the myocardium and blood vessels. The role of markers in identifying the risk group of adverse cardiovascular events remains unclear. Early diagnostics and determination of prognostic factors of cardiovascular toxicity, which develop after anticancer therapy of CLPD, are important and not solved problems. Conclusions. The prognosis for the development of cardiovascular events after antitumor treatment of CLPD remains unfavorable. Clinical monitoring, imaging methods, determination of the biomarker levels (natriuretic peptides, troponins) for cardiotoxicity risk stratification are recommended during antitumor treatment to identify early signs and risk of cardiotoxicity. The use of the latest biomarkers and their combinations may be a way to improve the assessment of the cardiotoxicity risk in CLPD. To date, there is no sufficient evidence on the feasibility of routine determining these biomarkers, which indicates the need to plan new studies.

Experimental investigation of supercontinuum generation in a birefringence tellurite microstructured optical fiber.

A four-hole birefringence tellurite microstructured optical fiber (BTMOF) was designed and fabricated based on 76.5T e O 2-6Z n O-11.5L i 2 O-6B i 2 O 3 glass, and its core (slow and fast axes were) measured to be approximately 4.74µm and 4.29µm, respectively. The experimentally measured results demonstrated that the maximum supercontinuum (SC) spectra extended from ∼914.1n m to ∼1885.1n m when the polarization state of the pump pulse was parallel to the fast axis at 1400nm with an average power of 460mW. We performed numerical simulations based on the nonlinear Schrödinger equation, which support the experimentally measured results. The SC generation in birefringent silica microstructured fiber with the same geometric parameters was simulated, and the results showed that the enhanced nonlinear refractive index of the BTMOF yielded a spectrum with a significantly larger bandwidth. Furthermore, the two polarization states along the fast axis and slow axis exhibit different dispersion characteristics, which provide a convenient way of tuning the properties of the generated SC. This work highlights BTMOF as a promising platform for the development of a SC light source, which can be widely used in food quality inspection, early cancer diagnostics, gas sensing, and high-spatial-resolution imaging.

Prognostic value of von Willebrand factor in clinical practice

The von Willebrand factor (vWF) is a multimeric plasma glycoprotein, which quantification has important prognostic value. The current literature review demonstrates a relationship between the disease severity and vWF level. For example, von Willebrand disease is characterized by a quantitative/qualitative genetic vWF deficiency resulting in potentially developed massive bleeding, which knowledge can prevent development of formidable complications. We should also not forget about an opportunity of developing acquired Willebrand syndrome most often occurring in response to autoimmune diseases. A marked vWF increase during pregnancy may evidence about developing preeclampsia, whereas in newborns exposed to additional risk factors, it can lead to thrombosis. In cancer patients, a substantially elevated vWF level correlates with low survival, especially in those with ovarian cancer, glioblastomas, esophageal and lung cancer. The emergence of a novel coronavirus infection COVID-19 allowed us to take a fresh look at prognostic value of vWF, because numerous studies show that increased blood plasma vWF:Ag is associated with more adverse outcome in patients with COVID-19. Here, we demonstrate an importance of determining vWF level, because early diagnostics and treatment can improve the outcomes of all such patients.

Accuracy of automated intracerebral hemorrhage volume measurement on non-contrast computed tomography: a Swedish Stroke Register cohort study

PurposeHematoma volume is the strongest predictor of patient outcome after intracerebral hemorrhage (ICH). The aim of this study was to validate novel fully automated software for quantification of ICH volume on non-contrast computed tomography (CT).MethodsThe population was defined from the Swedish Stroke Register (RS) and included all patients with an ICH diagnosis during 2016–2019 in Region Skåne. Hemorrhage volume on their initial head CT was measured using ABC/2 and manual segmentation (Sectra IDS7 volume measurement tool) and the automated volume quantification tool (qER–NCCT) by Qure.ai. The first 500 were examined by two independent readers.ResultsA total of 1649 ICH patients were included. The qER–NCCT had 97% sensitivity in identifying ICH. In total, there was excellent agreement between volumetric measurements of ICH volumes by qER–NCCT and manual segmentation by interclass correlation (ICC = 0.96), and good agreement (ICC = 0.86) between qER–NCCT and ABC/2 method. The qER–NCCT showed volume underestimation, mainly in large (> 30 ml) heterogenous hemorrhages. Interrater agreement by (ICC) was 0.996 (95% CI: 0.99–1.00) for manual segmentation.ConclusionOur study showed excellent agreement in volume quantification between the fully automated software qER–NCCT and manual segmentation of ICH on NCCT. The qER–NCCT would be an important additive tool by aiding in early diagnostics and prognostication for patients with ICH and in provide volumetry on a population-wide level. Further refinement of the software should address the underestimation of ICH volume seen in a portion of large, heterogenous, irregularly shaped ICHs.

Angiogenic factors (sFlt-1, PlGF) in twin pregnancy with placentaassociated complications

Aim : to determine reference values of angiogenic factors dynamics in pregnancy for female patients with twins and different types of placentation for early diagnostics and assessment of preeclampsia (PE) severity. Materials and Methods . There was conducted 2020–2021 prospective study enrolling 93 females with twin pregnancy to examine 68 with dichorionic diamniotic (DCDA) twins and 25 with monochorionic diamniotic (MCDA) twins. All patients were divided into 2 groups: group I consisted of 65 women with twin pregnancy without PE, group II included 28 women with twin pregnancy complicated by PE. In blood serum of pregnant women the level of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio were studied for diagnosing and predicting PE severity at 4 time points of gestation (20.0–23.6 weeks, 24.0–28.6 weeks, 29.0–33.6 weeks, 34.0–36.6 weeks). Results . No significant difference was found in angiogenic factors level and their ratio in pregnant women with uncomplicated DCDA and MCDA twins. Regardless of placentation type, sFlt-1/PlGF ratio in women with twin pregnancy and PE at 24 weeks of gestation was 103.3, by 20-fold exceeding this level than in uncomplicated twin pregnancy. Cut-off values for sFlt-1/PlGF ratio were determined allowing highly reliable to rule out diagnosis PE (sFlt-1/PlGF < 21.85; sensitivity 100 %, specificity 85 %) and to diagnose PE (sFlt-1/PlGF > 49.4; sensitivity 71.1 %, specificity 100 %). The sFlt-1/PlGF ratio was higher in pregnant women with severe PE compared with the moderate degree of the disease throughout pregnancy (р < 0.05). In pregnant women with early PE, the angiogenic factors ratio exceeded the upper threshold value from 24 weeks of gestation, with late PE – from 34.0–36.6 weeks. Significantly higher sFlt-1 level (18359 ± 8656 pg/ml vs. 5526 ± 2808 pg/ml; р < 0.001) and the sFlt-1/PlGF ratio (118,0 ± 65,2 vs. 32,8 ± 18,6; р < 0.03) as well as severe degree of PE were noted in patients with induced twin pregnancy from 24.0–28.6 weeks of gestation compared with spontaneous multiple pregnancy (42,2 and 22,2 % respectively; p < 0,05). Conclusion . The developed reference values of the sFlt-1/PlGF ratio in pregnant women with twins and different types of placentation can be used not only to diagnose PE, but also to assess the severity and timing of the disease manifestation.

Epidemiology of inherited epidermolysis bullosa in Germany.

Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity. Epidemiological data from different countries have been published, but none are available from Germany. In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization. Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries. Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.

Special Section Guest Editorial: Advances in High-Dimensional Medical Image Processing.

Guest Editors Ivana Išgum, Bennett A. Landman, and Tomaž Vrtovec introduce the JMI Special Section on Advances in High-Dimensional Medical Image Processing.

Platelet-Derived Biomarkers: Potential Role in Early Pediatric Serious Bacterial Infection and Sepsis Diagnostics.

Fever is the most common complaint of children who are attending a pediatric emergency department (PED). Most of the fever cases are of viral origin; however, the most common markers, such as leucocyte, neutrophil count, or C-reactive protein, are not sensitive or specific enough to distinguish the etiology of fever, especially if children present at the early phase of infection. Currently, platelets have been attributed a role as important sentinels in viral and bacterial infection pathogenesis. Thus, our aim was to analyze different platelet indices, such as PNLR (platelet-to-neutrophil/lymphocyte ratio), PNR (platelet-to-neutrophil ratio) as well as specific secreted proteins, such as sP-selectin, CXCL4, CXCL7, and serotonin. We included 68 children who were referred to PED with the early onset of fever (<12 h). All children with comorbidities, older than five years, and psychiatric diseases, who refused to participate were excluded. All the participants were divided into viral, bacterial, or serious bacterial infection (SBI) groups. All the children underwent blood sampling, and an additional sample was collected for protein analysis. Our analysis revealed statistically significant differences between leucocyte, neutrophil, and CRP levels between SBI and other groups. However, leucocyte and neutrophil counts were within the age norms. A higher PNLR value was observed in a bacterial group, PNR-in viral. As we tested CXCL7 and sP-selectin, alone and together those markers were statistically significant to discriminate SBI and sepsis from other causes of infection. Together with tachypnoe and SpO2 < 94%, it improved the prediction value of sepsis as well as SBI. CXCL4 and serotonin did not differ between the groups. Concluding, CXCL7 and sP-selectin showed promising results in early SBI and sepsis diagnosis.

An integrated lab-on-a-chip platform for pre-concentration and detection of colorectal cancer exosomes using anti-CD63 aptamer as a recognition element

Colorectal cancer (CC) is one of the common causes of cancer-related deaths around the globe. Identification of a novel biomarker for CC is of paramount importance for early diagnostics and reducing its mortality. Among the most promising biomarker candidates, exosomes hold great potential for cancer diagnosis, management, and treatment. Exosomes are extracellular vesicles secreted from cells and they contribute to the intercellular communication, immune response and the pathogenesis of many diseases including cardiovascular diseases, neurodegenerative diseases, and cancer. Several methods have been developed/utilized for exosome isolation and purification. However, these methods are time-consuming and have low purification efficiency. In this work, we developed the “apta-magnetic biosensor” platform for isolation, purification and detection of exosomes from cell culture. Anti-CD63 aptamer, which is conjugated to the surface of magnetic nanobeads, was used as a recognition element. A dynamic separation system was used which employs a transverse magnetic field along a microfluidic channel. The channel was exposed to an alternate magnetic field which imposes alternate magnetic force onto the magnetic bead-exosome complex. The combination of the fluid flow and magnetic force generates several “alternate trapping and releasing” events under continuous-flow conditions with each event representing a washing cycle. The graphene coated onto the surface of the magnetic nanobeads was used as a quencher for the fluorescently labeled aptamer (OFF state) in the absence of the target. Upon the addition of CD63 target protein, the aptamer dissociates from the graphene and binds to the target hence increasing the fluorescence intensity (ON state). A calibration plot of variable concentrations of exosomes vs fluorescence intensity was obtained and the detection limit was calculated as 1457 particles/mL. The specificity of the sensor was tested using closely associated proteins. The results showed that the aptamagnetic isolation, pre-concentration of exosomes and quantification demonstrate great potential for various clinical applications.

Mucormycosis - A Rare, yet Lethal Infection: A Review

Mucormycosis is an angio invasive infection caused by Mucorales fungi, which is mostly observed in diabetic and immunocompromised patients. The infection can be classified into cutaneous, rhino-orbito cerebral, gastrointestinal, disseminated and other rare pulmonary types. The overall mortality rate due to this infection has increased, even with aggressive treatment. Moreover, there has been a major mucormycosis outbreak in India following the deadly second wave of COVID-19 cases in the country. The epidemiology of mucormycosis is evolving due to advances in therapeutics and early diagnostics tools. The aim of this review is to provide an overview of the epidemiology, pathogenesis and types of mucormycosis along with an update on the recent advanced diagnostics tools and therapeutics to combat the rare, yet lethal infection.

Luminal and Tumor-Associated Gut Microbiome Features Linked to Precancerous Lesions Malignancy Risk: A Compositional Approach.

Colorectal cancer is the third most commonly diagnosed cancer worldwide. Human gut microbiome plays important roles in protecting against it, as well as contributing to its onset and progression. Identification of specific bacterial taxa associated with early stages of colorectal cancer may help develop effective microbiome-based diagnostics. For precancerous lesions, links of their characteristics to luminal and tumor-associated microbiome composition are to be elucidated. Paired stool and tumor brush biopsy samples were collected from 50 patients with precancerous lesions and early forms of colon cancer; their microbial communities were profiled using high-throughput 16S rRNA sequencing. We showed that the microbiome differences between stool and biopsy samples can be to a high extent computationally corrected. Compositionality-aware statistical analysis of microbiome composition revealed its associations with the number of lesions, lesion type, location and malignization pathway. A major determinant of precancerous lesions malignancy risk-the number of lesions-was positively associated with the abundance of H2S-producing taxa. Our results contribute to the basis for developing early non-invasive colorectal cancer diagnostics via identifying microorganisms likely participating in early stages of cancer pathogenesis.

Noninvasive Diagnostics of Renal Amyloidosis: Current State and Perspectives.

Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses, the disease is related to increased levels and/or abnormal synthesis of certain proteins in the organism due to pathological processes, e.g., monoclonal gammopathy and chronic inflammation in rheumatic arthritis. Treatment of amyloidoses is focused on reducing amyloidogenic protein production and inhibition of its aggregation. Therapeutic approaches critically depend on the type of amyloidosis, which underlines the importance of early differential diagnostics. In fact, the most accurate diagnostics of amyloidosis and its type requires analysis of a biopsy specimen from the disease-affected organ. However, absence of specific symptoms of amyloidosis and the invasive nature of biomaterial sampling causes the late diagnostics of these diseases, which leads to a delayed treatment, and significantly reduces its efficacy and patient survival. The establishment of noninvasive diagnostic methods and discovery of specific amyloidosis markers are essential for disease detection and identification of its type at earlier stages, which enables timely and targeted treatment. This review focuses on current approaches to the diagnostics of amyloidoses, primarily with renal involvement, and research perspectives in order to design new specific tests for early diagnosis.

КРИТЕРИИ ПРОГНОЗИРОВАНИЯ РИСКА РАЗВИТИЯ ЗАБОЛЕВАНИЙ С ЛИМФОПРОЛИФЕРАТИВНЫМ СИНДРОМОМ У ДЕТЕЙ

336 children with lymphoproliferative syndrome were examined to determine and develop criteria for predicting the risk of developing the primary form of Epstein-Barr viral infection, recurrent respiratory diseases, adenovirus infection.
 On the basis of the obtained results, criteria were developed for predicting individual risk of developing diseases with lymphoproliferative syndrome, the main parameters of which were significant risk factors revealed during the study. The method of prediction of risk and early diagnostics of diseases with lymphoproliferative syndrome convenient in use to pediatricians, infectologists and specialists of medical institutions, which allows to isolate children with high risk of developing lymphoproliferative syndrome and to diagnose in a timely manner the primary form of Epstein-Barr viral infection, recurrent respiratory diseases, adenovirus infection tonsillary form.

Comment on Kesić et al. Early Diagnostics of Vulvar Intraepithelial Neoplasia. Cancers 2022, 14, 1822.

We have read with great interest the paper by Kesić, V. et al. entitled "Early Diagnostics of Vulvar Intraepithelial Neoplasia" [...].