Background Of Immunodeficiency Research Articles

IMMUNOLOGICAL STATUS OF THE CALVES BORN FROM THE COWS WITH CHRONIC SYSTEMIC INFLAMMATION SYNDROME

This article presents the results of a study of the effect of chronic systemic inflammation syndrome in pregnant cows on the immunological status of newborn calves. It has been established that the calves obtained from the cows with this syndrome have intense colostral immunity against the background of congenital immunodeficiency, which is characterized by a decrease in the number of T- and B-lymphocytes, the activity of phagocytes, lysozyme and the complement system. The identified abnormalities in this group of animals increase the risk of early neonatal infection and comorbid pathology.

Evaluation of the effectiveness of the proposed therapy on energy metabolism parameters in patients with chronic liver lesions on the background of secondary immunodeficiency state

Objective: to study the effect of a combination of azoximer bromide (AB) and human placenta hydrolysate (HPН) on metabolic processes in patients with chronic liver lesions on the background of secondary immunodeficiency. Materials and methods: 95 patients with chronic liver pathology on the background of secondary immunodeficiency (VIDS) aged 35 to 56 years were examined. The main group is 45 people, and the comparison group is 50 people. After a general clinical and bacteriological examination, all patients were subjected to the study of metabоlic processes. The assessment of metabolic disorders was carried out by the level of macroergic compounds in the hemolysate of the washed suspension of erythrocytes of patients by thin-layer chromatography. In addition to treatment with conventional methods, patients who were under observation were additionally prescribed a combination of drugs — bromine azoximer and human placenta hydrolysate. Patients of the comparison group received milk thistle preparations as a hepatoprotector and did not use any immunoactive drugs. Results: when studying the state of indicators of metabolic disorders after the completion of treatment, it was found that patients in the main group who received AB and HPН had almost complete normalization on the part of the studied indicators, which cannot be said about patients from the comparison group who received only conventional drugs in average therapeutic doses in the treatment complex. Conclusions: from the data obtained, it is possible to judge the positive effect of AB and HPН on the indicators of the state of energy homeostasis and consider it pathogenetically justified and clinically promising to include their combination in the complex of treatment of patients with CLP against the background of VIDS.

Сравнительная оценка эффективности кормовых добавок на основе торфосапропелевого концентрата при выращивании бройлеров

Abstract. Modern conditions for the development of poultry farming increase the impact of technological stress on the poultry body, which contributes to the development of immunodeficiency conditions in them. Against the background of immunodeficiency, diseases of various etiologies develop, which reduces the efficiency of the industry. To offset the negative result of technological and other types of stress, the search for effective means of domestic production is carried out, which is especially important in the conditions of priority use of alternative import-substituting means. The search for effective means that meet all the requirements of prevention remains to this day an urgent issue of practical veterinary medicine. Feed additives with a wide spectrum of action act as such agents. Often such feed additives act as adaptogens. In this regard, the purpose of this study was to compare the effectiveness of feed additives prepared on the basis of peat sapropel concentrate mixed with known mineral and probiotic components. The objectives of the study were: to evaluate the effectiveness of disease prevention; causes of morbidity and mortality; livestock safety and improving the quality of fattening. Methods. To assess the effectiveness of the tested domestic feed additives, clinical, pathomorphological, histological studies were carried out in accordance with the zoohygenic conditions of poultry keeping and statistical methods for evaluating the results obtained. As a result of the conducted studies on the preventive feeding of feed additives based on peat sapropel concentrate of domestic production, their immuno- and organoprotective effect was revealed. Scientific novelty. For the first time, a comparative assessment of various feed additives based on peat-sapropel concentrate for the prevention of stress, various diseases, livestock safety and live weight gain of broilers at macro- and microscopic levels was carried out.

Arabidopsis translation initiation factor binding protein CBE1 negatively regulates accumulation of the NADPH oxidase respiratory burst oxidase homolog D

Cell surface pattern recognition receptors sense invading pathogens by binding microbial or endogenous elicitors to activate plant immunity. These responses are under tight control to avoid excessive or untimely activation of cellular responses, which may otherwise be detrimental to host cells. How this fine-tuning is accomplished is an area of active study. We previously described a suppressor screen that identified Arabidopsis thaliana mutants with regained immune signaling in the immunodeficient genetic background bak1-5, which we named modifier of bak1-5 (mob) mutants. Here, we report that bak1-5 mob7 mutant restores elicitor-induced signaling. Using a combination of map-based cloning and whole-genome resequencing, we identified MOB7 as conserved binding of eIF4E1 (CBE1), a plant-specific protein that interacts with the highly conserved eukaryotic translation initiation factor eIF4E1. Our data demonstrate that CBE1 regulates the accumulation of respiratory burst oxidase homolog D, the NADPH oxidase responsible for elicitor-induced apoplastic reactive oxygen species production. Furthermore, several mRNA decapping and translation initiation factors colocalize with CBE1 and similarly regulate immune signaling. This study thus identifies a novel regulator of immune signaling and provides new insights into reactive oxygen species regulation, potentially through translational control, during plant stress responses.

Determination of aspergillosis of the female genital organs in women with immunodeficiency

Background. Morphological diagnosis of aspergillosis sometimes poses great difficulties due to the fact that molds of the genus Aspergillus are very sensitive to the use of antimicrobial therapy and change under its influence. In this regard, we provide information about aspergillosis of the female genital organs, discovered accidentally during an autopsy. The purpose of the study is to conduct a complex pathomorphological analysis of biopsy, operative and sectional gynecological material of women with secondary immunodeficiency conditions, for early diagnosis of aspergillosis (which is the key to a favorable outcome of the disease), differential diagnosis and detection of invasive forms of aspergillosis. Materials & Methods. We analyzed the autopsies of 4,796 women who died in Odesa region from 2009 to 2022. Autopsies revealed 7 cases of aspergillosis with damage to the female reproductive system. All of them were found in women who had confirmed HIV infection. In 5 cases, women additionally suffered from chronic alcoholism. Results. Based on the results of these cases, it can be stated that the detection of characteristic mycelium in the preparations is a reliable sign of aspergillosis, but their absence does not deny this disease. Aspergillus hyphae change as the process develops: they can be weakly stained, and with dystrophic phenomena and the presence of necrotic fragments of mycelium, it can be almost colorless when using hematoxylin and eosin. While necrosis, tissue detritus is observed in the center of the granuloma, fibrous structures, fungal hyphae are formed perifocally. To confirm the diagnosis, it is important to detect granulomatous productive inflammation, conidial heads, inflammatory infiltration, microabscesses, foci of calcifications. However, against the background of immunodeficiency, it is not always possible to see the "classic morphological picture" of aspergillosis. In addition, detection of characteristic mycelium is possible only in a proportion of patients. Conclusions. When examining the autopsy material of deceased women with immunodeficiency states, attention should be paid to the specific etiology of inflammatory processes of the reproductive system and the nature of the inflammatory process, the presence of Aspergillus hyphae and mycelia. The presence of morphological changes characteristic of aspergillosis allows to conduct a diagnostic search in the right direction. Detection of an invasive form of aspergillosis may indicate the presence of an immunodeficient state. Keywords: aspergillosis, female reproductive system, immunodeficiency state, HIV infection, uterus, mammary gland, drug addiction.

CO-INFECTION WITH HERPESVIRUSES AS A NEW ASPECT OF TUBERCULOSIS IN CHILDREN

The increase in the incidence of tuberculosis in adults in recent years leads to negative changes in the epidemiological situation among children. Tuberculosis infection is often found against the background of various chronic pathologies. It has been established that the activation of opportunistic, especially herpetic, infections increases the risk of infection with MBT. Tuberculosis, in turn, has a clinically more severe course against the background of secondary immunodeficiency. In childhood, the immaturity of the immune system is added, which in turn can also serve as a prerequisite for the progression of the tuberculosis process. A so-called vicious circle is formed - a persistent, latent herpes infection leads to the appearance of an immunodeficiency state, in turn, mycobacterium tuberculosis – contributes to the further deepening of immunological dysfunction, which leads to the development of the syndrome of violation of anti-infective protection and creates the basis for the progression of the tuberculosis process. Currently, the actual goal of scientific research is to establish the specific weight of herpesvirus infections among tuberculosis patients, their impact on the occurrence, spread and course of various forms of tuberculosis, the study of virological, immunological and clinical-epidemiological aspects of the problem of co-infection of tuberculosis and herpesviruses. The resolution of the issue of combined infection as a new aspect of tuberculosis can play a decisive role in the effective diagnosis and prediction of the severity of the course of tuberculosis in childhood at the current stage and will improve the epidemiological situation with tuberculosis in general.

Microbiological properties of opportunistic saccharomycetes of the genus <i>Candida</i> in chronic, recurrent infectious inflammatory processes (literature review)

Literature review involves a problem analysis of current scientific publications on yeast-like fungi of the genus Candida of the family Saccharomycetaceae. In 90% of cases, the etiological factor of chronic, recurrent infectious and inflammatory processes is represented by residents of oral, intestinal, urogenital and skin microbiome, opportunistic Candida albicans fungi. The paper considers the relevant medical and social problem of endogenous opportunistic infections on the example of candidiasis (candidamycosis). The review presents a conceptual analysis of changes in the microbiological properties of clinically significant candida species with ubiquitous distribution: Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, Candida parapsilosis, Candida dubliniensis, Candida auris. The authors provide a current perspective on the risk of superficial and invasive candidomycosis as an opportunistic, non-cyclic infection. Signs of the same type of pathological process develop with the participation of different species of opportunistic fungi in monoculture and associations against the background of immunodeficiency.

Generation and characterization of an immunodeficient mouse model of mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an inherited X-linked recessive disease caused by deficiency of iduronate-2-sulfatase (IDS), resulting in the accumulation of the glycosaminoglycans (GAG) heparan and dermatan sulfates. Mouse models of MPS II have been used in several reports to study disease pathology and to conduct preclinical studies for current and next generation therapies. Here, we report the generation and characterization of an immunodeficient mouse model of MPS II, where CRISPR/Cas9 was employed to knock out a portion of the murine IDS gene on the NOD/SCID/Il2rγ (NSG) immunodeficient background. IDS-/- NSG mice lacked detectable IDS activity in plasma and all analyzed tissues and exhibited elevated levels of GAGs in those same tissues and in the urine. Histopathology revealed vacuolized cells in both the periphery and CNS of NSG-MPS II mice. This model recapitulates skeletal disease manifestations, such as increased zygomatic arch diameter and decreased femur length. Neurocognitive deficits in spatial memory and learning were also observed in the NSG-MPS II model. We anticipate that this new immunodeficient model will be appropriate for preclinical studies involving xenotransplantation of human cell products intended for the treatment of MPS II.

Clinical guidelines in the pathology of some pet lizard species

Keeping different species of lizards as pets means the development of artificial environments, terrariums or aquateraria, which offer conditions as close as possible to those in the natural environment, as well as the development of appropriate feeding systems. In the category of pet lizards we include: chameleons, agamids, iguanas, skinks, anoles, lizards or geckos. There are extremely different categories of lizards in terms of environmental and feeding requirements and with a special ecobiology, sometimes characteristic of a single species or of several species within a genus. Maintenance deficiencies are most frequently translated by metabolic disorders, frequently associated with infections or parasites that are not diagnosed in individuals of the same species living in the natural environment. In general, a series of viruses or bacterioses overlaped on an immunodeficient background that appears as a result of improper feeding or defective environmental parameters.

Проявления ВИЧ-инфекции в полости рта у пациентов в зависимости от содержания CD4+ Т-лимфоцитов в крови

Objective - analysis and generalization of the available data on the manifestations of human immunodeficiency virus in the oral cavity depending on the number of CD4+ T-lymphocytes in the blood. Materials and methods. A search of clinical studies, systematic reviews, and online meta-analyses was conducted from 2004-2023 in the PubMed, Elsiever, Scopus, Cochrane, and Elibrary databases, which described oral manifestations of HIV infection as a function of CD4+ T-lymphocyte count. Results. Pseudomembranous candidiasis, hairy leukoplakia, Kaposi's sarcoma, and non-Hodgkin's lymphoma develop against a background of severe immunodeficiency when the CD4+ T-lymphocyte count is <200 cells/μL blood. Kaposi's sarcoma also develops in people with a high CD8+ T-lymphocyte count (>1000 cells/μL of blood) or with a low CD4+ to CD8+ ratio (CD4+:CD8+ ≤0.5). Non-Hodgkin's lymphoma develops not only with CD4+ T-cells <200/μL, but also with a high number of CD8+ T-cells (≥2000 cells/μL of blood). Specific periodontal disease develops with moderate to severe immunodeficiency (CD4+ T-cells 200-500 cells/μL of blood). Necrotic ulcerative gingivitis is more often seen in severe immunodeficiency (CD4+ T-lymphocytes <200 cells/μL). Conclusion. The development of pseudomembranous candidiasis (p<0,05), "hairy" leukoplakia (p<0,01), Kaposi sarcoma (p<0,0001) statistically significantly correlates with CD4+ T-lymphocyte count <200 cells/μl blood. In addition, the development of Kaposi's sarcoma, in addition to the low number of CD4+ T-cells, is affected by a high number of CD8+ cytotoxic lymphocytes >1000 cells/μL (p=0.0003) and a low CD4+:CD8+ ratio ≤0.5 (p<0.0003), which is statistically significant.

Cardiac Involvement in Children Affected by COVID-19: Clinical Features and Diagnosis

COVID-19 (Coronavirus disease 2019) in children is usually mild. However, multiple organ disorders associated with SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) have been detected with poor respiratory symptoms. Cardiac changes are noted in 17% to 75% of cases, which are associated with diagnostic difficulties in high-risk groups for the development of complications that are associated with myocardial damage by the SARS-CoV-2 virus. The objective of this review is to identify the most significant symptoms of cardiac involvement affected by COVID-19, which require in-depth examination. The authors analyzed publications from December 2019 to the October 2022, which were published in accessible local and international databases. According to the analysis data, the main sign of myocardial involvement was increasing as cardiomarkers in the patient's blood, in particular troponin I or troponin T. Many authors noted that the increased level of CRP (C-reactive protein) and NT-proBNP, which are accompanied by changes in the ECG (electrocardiogram) and EchoCG (echocardiography), as a rule, were nonspecific. However, the identified cardiac functional dysfunctions affected by SARS-CoV-2, required an cardiac MRI. The lack of timely diagnosis of myocardial involvements, especially in children at high risk for the development of complications associated with SARS-CoV-2 myocardial injury, can lead to death. The direct damage of the structural elements of myocardial blood vessels in patients with severe hypoxic changes resulted from respiratory failure caused by SARS-CoV-2 lung damage, with the development of severe acute diffuse alveolar damage and cell-mediated immune response and myocardial involvement affected by SARS-CoV-2 damage. In this article, the authors introduce a clinical case of a child who dead from inflammatory myocardities with COVID-19 in a background of congenital heart disease and T-cell immunodeficiency.

Trends and morphologic variants of Kaposi Sarcoma as seen in Nnewi, Anambra State, Nigeria

Kaposi sarcoma (KS) is a human herpes virus type 8 (HHV-8) driven neoplasm with varying morphologic features and attendant diagnostic dilemma. This study presents the trend of KS in our environment and the different morphologic variants, with a view to arousing awareness and reducing missed and delayed diagnosis. KS accounted for 18.34% and 59.66% of vascular neoplasms and malignant vascular neoplasms, respectively with most KS occurring in the background of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The frequency peaked in 2013 and began to decline with a fairly even sex distribution. There are diverse variants of KS that can pose diagnostic challenges. Hence, there is need for this awareness to enhance prompt and accurate diagnosis.

New coronavirus infection in a child at the age of 2 years 4 months with acute lymphoblastic leukemia (fatal case)

Children get sick less often than adults with a new coronavirus infection (in the Russian Federation, they account for 7.6% of registered cases of COVID-19), with less severe clinical symptoms, they require hospitalization less often, their disease is milder. The frequency of severe and extremely severe cases of COVID-19 in children does not exceed 1%. A clinical case of the course of COVID-19 in a child aged 2 years 4 months is presented. with acute lymphoblastic leukemia. A feature of the presented case is the development of an extremely severe new coronavirus infection in a child with secondary immunodeficiency caused by a long-term course of malignant, treatment-resistant of acute lymphoblastic leukemia. Slow, within 3 months, the development of the infectious process with long-term preservation of normal indicators of the function of the respiratory system led to the formation of viral-bacterial pneumonia with the development of respiratory distress syndrome. Despite the modern complex of therapeutic measures, severe comorbidity led to the development of DIC and multiple organ failure, which was the direct cause of the childs death. A possible therapy strategy is discussed in a patient with severe comorbidity against the background of secondary immunodeficiency and long-term persistence of SARS-CoV-2 in the presence of IgG antibodies to SARS-CoV-2 in the blood. For the first time, data on morphological changes in the lungs with a long course of COVID-19 (more than 100 days) in a young child are presented.

Triple-negative transformation of the endometrium, cervix and mammary gland on the background of immunodeficiency

Precancerous processes of the female reproductive system continue to be an issue that is being actively studied, despite the successes of recent years. One of the key prognostic factors is the characterization of the receptor set, primarily the mammary gland and endometrium, namely estrogen (ER), progesterone (PR), epidermal growth factor-2 (HER2) receptors. Purpose – to identify the features of the distribution of estrogen, progesterone and epidermal growth factor receptors in the tissues of the endometrium, cervix and mammary gland with a combination of HIV infection and alcohol abuse. Fifty women of reproductive age from 20 to 40 years were studied. After routine conduction and immunohistochemical staining, ER and PR expression were determined by a modified D.Allred scale. HER2 expression was determined by a semi-quantitative method. The obtained digital data were statistically processed. A morphometric study indicates that the combination of HIV infection and alcohol abuse significantly affects the distribution of receptors in the female reproductive system. To a greater extent, the overall score is reduced by reducing the number of cellular elements with the expression of ER and PR. HER2 receptor expression is significantly reduced in the endometrium and mammary gland. These changes may be facilitated by atrophic changes in these organs, which occurs in immunodeficiency. According to the D.Allred scale, the mean score decreases from 5.45±0.63 to 3.10±0.88 in the endometrium, from 4.68±0.65 to 2.47±0.58 in the cervix, from 6.57±0.67 to 3.57±0.77 in the mammary gland (p<0.05). HER2 expression decreased from 3.24±0.47 to 2.21±0.23 in the endometrium, from 3.43±0.66 to 2.36±0.32 in the mammary gland (p<0.05). The development of immunodeficiency is characterized by the restructuring of female reproductive organs with a change in the receptor set of the endometrium, cervix and mammary gland and a decrease in both the qualitative and quantitative composition of the receptors, which may serve as a prerequisite for the development of a triple-negative phenomenon in tumors of these organs.

Abstract 5599: A novel orally available anti-cancer drug candidate, SB17170, represses myeloid-derived suppressor cells by targeting HMGB1

Abstract Introduction: High Mobility Group Box1 (HMGB1) is a kind of DAMP to modulate immune responses in various conditions, including the tumor microenvironment. In various cancers, it has been reported that cytoplasmic localization of HMGB1 is correlated with poor prognosis. Here, we present a novel small-molecule drug candidate, SB17170, which inhibits immune-suppressive cells in tumor microenvironments by specific binding to HMGB1. Methods: SB17170 is a pro-drug of active metabolite SB1703 which was identified in cell-based phenotypic screening. SB1703 modulates immune responses by inhibiting the secretion of various cytokines from activated macrophages. HMGB1 was revealed as the target protein of SB1703 using Fluorescence difference In Two-dimensional Gel-Electrophoresis (FITGE). The antitumor activity of SB1703 was analyzed in B16F10 murine syngeneic model. Results: SB17170 is orally available drug candidate at the clinical development stage for solid tumors. The active metabolite SB1703, bound to HMGB1, was observed in activated MDSC, but not in immature MDSC, and inhibited the activity and cytokine release of MDSC at the submicromolar range. The antitumor activity of SB17170 was observed in B16F10 murine syngeneic model, but not in immunodeficient NOG model, suggesting that SB17170 requires the adaptive immune system for its antitumor activity. The oral treatment of SB17170 in tumor-bearing mice induced intratumor T cell infiltration, but reduced the number of MDSC from day 3. SB17170 also repressed HMGB1 levels as well as MDSC in the blood. In combination with immune checkpoint inhibitors against PD1, PD-L1, and CTLA4, SB17170 enhanced the antitumor responses. Conclusions: We presented here orally available small-molecule drug candidate, SB17170, which selectively binds to HMGB1 and represses MDSC in tumor microenvironment. SB17170 showed the antitumor activity in B16F10 murine syngeneic models, but not in immunodeficient background, suggesting that its mechanism of action is based on antitumor immune responses. Citation Format: Young Il Choi, Sungoh Ahn, Hyo Young Kim, Na Jin Jung, Jae Jin Lee, Seung Bum Park. A novel orally available anti-cancer drug candidate, SB17170, represses myeloid-derived suppressor cells by targeting HMGB1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5599.

Mogamulizumab induces long-term immune restoration and reshapes tumour heterogeneity in Sézary syndrome.

Mogamulizumab, an anti-CCR4 monoclonal antibody, has been shown to increase progression-free survival in cutaneous T-cell lymphoma. We hypothesized that besides the targeted depletion of Sézary cells (SCs), mogamulizumab may reshape the immune tumour microenvironment. Both malignant and benign compartments from 26 patients with B2 stage Sézary syndrome before mogamulizumab initiation were prospectively analysed using KIR3DL2 and TCRVβ markers, serological markers and molecular assessments of clonality. Prior to mogamulizumab, the benign subset of CD4+ T cells displayed exhausted phenotypes, with an increased gradient in programmed death-1, TIGIT, DNAM-1, CD27, CD28 and CD70 expression from age-matched controls to patients' benign CD4+ T cells and to SCs. All patients presented SCs with heterogeneous phenotypes, and differential expression of individual markers was found within distinct malignant subsets. Early complete blood response was observed in 17 of 26 patients and was associated with higher baseline CCR4 expression. A drastic decrease in benign T cells and activated regulatory T-cell counts was observed during the first 4 weeks. Long-term follow-up revealed the emergence of an immune restoration involving CD8+ and naive and stem memory CD4+ T cells, with almost complete disappearance of exhausted lymphocytes. Development of resistance or tumour escape to mogamulizumab was associated with the emergence of CCR4- SCs in blood and skin, displaying significant changes in their heterogeneity patterns, and not explained only by mutations within CCR4 coding regions. Mogamulizumab likely contributes to the restoration of efficient immunity and reshapes not only the malignant lymphocyte subset but also the benign subset. These results have potential implications for optimal therapeutic sequences and/or combinations. What is already known about this topic? Management of Sézary syndrome (SS) involves successive therapies that participate as cause and consequence in the emergence of resistant clones, on a background of immunodeficiency. We and others have reported the complex and dynamic heterogeneity of Sézary cells (SCs) during disease progression. Mogamulizumab therapy, by targeting the skin-homing receptor CCR4, mainly expressed by SCs, has been shown to increase progression-free survival in patients with SS. What does this study add? Using multicolour flow cytometry, we provide quantification of CCR4 and immune checkpoint molecules on malignant SCs and benign CD4+ T cells from patients with SS, separated using KIR3DL2 and TCRVβ expression. Mogamulizumab is not only aimed at eradicating malignant SCs but potentially contributes to the restoration of efficient immunity. Tumour escape is associated with the emergence of CCR4- SCs, not explained only by mutations within CCR4 coding regions.

Clinical Profile and Outcomes of Primary Immunodeficiency and Malignancy in Childhood at a Tertiary Oncology Center in Developing Country

Primary immune deficiencies are a group of heterogenous genetic disorders characterized by frequent infections, autoimmunity and malignancy. In this study, we aimed to evaluate clinical characteristics, outcomes of children with malignancy developed on background of primary immunodeficiency and compare survival rates of patients between malignant lymphoma with primary immunodeficiency and without immunodeficiency from tertiary oncology center in a developing country. A total 23 patients with primary immunodeficiency and malignancy were evaluated retrospectively. A total of 26 malignancies (first or second) in 23 patients were determined. The median age at the time of the first malignancy was 8 years (ranges 2–18 years) with increased male ratio (M/F:14/9). Non-Hodgkin lymphoma (n = 17; 65%) was the most common malignancy, followed by Hodgkin lymphoma (n = 5), anaplastic ependymoma (n = 1), spinal glioblastoma multiforme (n = 1), retinoblastoma (n = 1) and intracranial hemangiopericytoma (n = 1). The median follow-up time of patients was 25 months (ranges between 1 and 189 months). The 5-year overall survival rate of patients with malignant lymphoma associated with primary immunodeficiency (41%) were lower than immunocompetent patients with malignant lymphoma (80%) (p = 0.000). The 5-year overall survival of patients was diagnosed between 2021 and 2013 years (62%) was higher than previous years (22%) (p = 0.03). In conclusion, non-Hodgkin lymphomas were the most common histopathologic type in patients with malignancy associated with primary immunodeficiency in the present study. The survival of patients with malignant lymphoma associated with primary immunodeficiency has improved in recent years, yet it is still lower than immunocompetent patients with lymphoma and new targeted drugs are required for better survival rates.

Problems of metastasis (literature review)

Despite significant successes in the development of medical sciences, the study of oncopathology issues still occupies a leading place due to the identification of a large number of advanced cases of the disease. Firstly, this may be due to the rapid growth of a malignant tumor, for example, against the background of immunodeficiency. Secondly, with late treatment of patients, when they already have distant metastases. The success of treatment of any oncological process primarily depends on the timing of the diagnosis: the earlier the tumor is diagnosed, the greater the chance of a positive outcome and an increase in the life expectancy of the cancer patient. The most formidable complication of oncopathology and the main cause of death from it is metastasis, which often reduces to zero all the effects of therapy. Metastasis remains a mystery today. So, despite the large number of various theories, the question of the spread of the tumor throughout the body has not yet been resolved. There is no definite answer to the question: do metastases metastasize? The mechanisms of the influence of hormones on the processes of metastasis have not been fully studied. Difficulties in diagnosis are associated with the lack of clinical manifestations before the appearance of metastases, the inability to track and compare changes in tissues and organs in vivo, the non-specificity of the results of available research methods, and the lack of control of the spread of metastases throughout the body. Experimental studies on laboratory animals can provide answers to these and many other questions. In a review of the literature, a study of the main issues of metastasis is conducted.

Mouse model of voluntary movement deficits induced by needlestick injuries to the primary motor cortex

BackgroundMotor handicap is prevalent in patients with traumatic brain injury, but currently. there is a challenging task to prevent the degeneration of motor neurons and to fully recover the. voluntary movement after injury. New methodFor the first time, we propose to apply needlestick injuries to the primary motor cortex to create mouse model of voluntary movement deficits. Rotarod test, cylinder test and forepaw grip strength test were used to assay motor coordination of both C57BL/6 J and the triple immunodeficient NCG mice. Immunofluorescence staining of PKC-gamma, UCHL1, GFAP, Iba1 and Fluoro-Jade C was performed to analyze the numbers of motor neurons, microglia, astrocytes and degenerating neurons. ResultsMice on either C57BL/6 J or immunodeficient background with the unilateral primary motor cortex injury exhibit motor neuron death, activation of glial cells and deficits in voluntary movement. ConclusionsThe main finding of this study was that the unilateral primary motor cortex injured by needlesticks leads to reactive gliosis, motor neuron death and voluntary movement deficits in mice. This needlestick injury model of primary motor cortex might be useful for future exploration of underlying mechanisms of motor neuron degeneration and of promising treatment modalities such as cell transplantation to improve locomotor deficiency following neurotrauma.

Инфузионная терапия при пневмонии: что нового?

В связи с увеличением заболеваемости пневмонией, ее тяжелым течением и развитием осложнений, смешанной вирусно-бактериальной этиологией, а также объявлением Всемирной организацией здравоохранения COVID-19 пандемией были разработаны современные гайдлайны по клинике, течению, лечению, применению респираторной поддержки и реабилитации больных COVID-19. Особенностью течения тяжелых пневмоний является быстрое развитие острого респираторного ди­стресс-синдрома на фоне иммунодефицита. Представлены данные обзора литературы по лечению больных пневмонией: взгляды на потребность в инфузионной терапии и ее осложнения, применение вазопрессоров. Приведены сведения о лечении больных с синдромом эндогенной интоксикации и четкие показания к применению симпатомиметиков при септическом шоке. Представлены исследования, которые показали, что применение Реосорбилакта в комплексной терапии позволяет уменьшить частоту развития острого респираторного дистресс-синдрома, объем инфузии, необходимый для стабилизации гемодинамики, способствует перемещению жидкости из интерстиция в кровяное русло, выведению избытка жидкости, позволяет уменьшить уровень основных маркеров интоксикации. Такие свойства Реосорбилакта свидетельствуют о положительном эффекте его использования в комплексной терапии пневмоний и при септическом шоке.