Organ Pathology Research Articles

Efficacy of the Whole Plant Ethanol Extract of Phyllanthus Amarus on Trypanosoma Brucei-Induced Pathology in Wistar Rat

African animal trypanosomiasis is one of the most important protozoal diseases affecting animal health and production. This study was conducted to assess the phytochemical composition of Phyllanthus amarus ethanol extract and to assess its safety and efficacy on Trypanosoma brucei-induced pathology in Wistar rats. The plant sample was obtained from around the residential area in Ahmadu Bello University, main campus, Zaria, Nigeria, and subjected to phytochemical screening following standard procedures. Sixteen Wistar rats were divided into five groups, each rat in the groups receiving 0.1 mL of 10⁶ T. brucei trypomastigotes. After three days of patency, rats in groups III to V were given different plant extract treatments for four days, while rats in groups I and II served as negative and positive controls. Following treatment, clinical parameters, parasitaemia, gross pathology and biochemical analysis were observed and recorded. The results showed that the ethanol extract contained primary constituents such as alkaloids, phenols, cardiac glycosides, saponins, carbohydrates, triterpenes, anthraquinones, tannins, and steroids. The extract was found to be non-toxic and orally safe for Wistar rats. It showed moderate suppressive ability against parasitaemia, ameliorating fever, weight loss, and anaemia in Trypanosoma brucei-infected rats. It also demonstrated significant modulatory activity in reducing internal organ pathologies, liver enzyme pathology, and oxidative stress in the heart, kidney, and spleen. The study highlights the safety and efficacy of Phyllanthus amarus ethanol extract in managing African animal trypanosomiasis.

Abstract 16713: Pre-Clinical 30-day Survival Results of the BiVACOR TAH

Introduction: The BiVACOR Total Artificial Heart (TAH) replaces the failing heart with a durable and physiologically adaptive pump, which combines magnetic levitation and rotary blood pump technology. The pump has large clearances to minimize shear stress, generates pulse pressure via cyclic changes in pump speed, and modulates total outflow based on physiological conditions. A single rotor design enables a small pump size. Aim: Primary endpoint was survival at 30 days with normal end-organ function and absence of device related thromboembolism at necropsy. Methods: Five calves (82 - 108 kg) were implanted with the BiVACOR TAH and underwent continuous hemodynamic monitoring for 30 days. The pumps ability to generate a pulse pressure, balance outflow to the systemic and pulmonary circulations and to increase outflow in response to increased physical activity was assessed. Hemocompatibility and end-organ function were routinely monitored. Necropsy was performed on day 30 to evaluate for evidence of thromboembolism and end organ damage. Explanted pumps were examined. Results: All five calves survived to 30 days with normal end-organ function. Stable hemodynamics were achieved with normal pressures in the aorta and left and right atrium (MAP 111 ± 6 mmHg, CVP 12 ± 5 mmHg, LAP of 20 +/- 5 mmHg). Average estimated pump output was 12 ± 2 L/min with average pulse pressure of 30 mmHg. Pump output increased during changes in daily physiological condition (10 to 14 L/min). No device-related thromboembolism or other end organ pathologies were detected at necropsy. All explanted pumps were free of internal pump thrombus. Hemocompatibility was demonstrated (pfHb 4.34 ± 0.74 mg/dL). Bypass time decreased by 34 minutes over the entire study cohort. Conclusion: The BiVACOR TAH demonstrates normal hemodynamics including left/right balance. Pump design allows for a normal pulse pressure, increased pump output in response to exercise, and excellent hemocompatibility without device-related thromboembolism. Operative time markedly improves with surgeon experience. The small pump size may expand the use of TAH to smaller patients. This device may address the need for select patients with advanced heart failure who require biventricular support.

Novel biomarker discovery through comprehensive proteomic analysis of lupus mouse serum

ObjectivesThe difficulty of monitoring organ-specific pathology in systemic lupus erythematosus (SLE) often complicates disease prognostication and treatment. Improved non-invasive biomarkers of active organ pathology, particularly lupus nephritis, would improve patient care. We sought to validate and apply a novel strategy to generate the first comprehensive serum proteome of a lupus mouse model and identify mechanism-linked lupus biomarker candidates for subsequent clinical investigation. MethodsSerum levels of 1308 diverse proteins were measured in eight adult female MRL/lpr lupus mice and eight control MRL/mpj mice. ELISA validation confirmed fold increases. Protein enrichment analysis provided biological relevance to findings. Individual protein levels were correlated with measures of lymphoproliferative, humoral, and renal disease. ResultsFour hundred and six proteins were increased in MRL/lpr serum, including proteins increased in human SLE such as VCAM-1, L-selectin, TNFRI/II, TWEAK, CXCL13, MCP-1, IP-10, IL-10, and TARC. Newly validated proteins included IL-6, IL-17, and MDC. Results of pathway enrichment analysis, which revealed enhancement of cytokine signaling and immune cell migration, reinforced the similarity of the MRL/lpr disease to human pathology. Fifty-two proteins positively correlated with at least one measure of lupus-like disease. TECK, TSLP, PDGFR-alpha, and MDC were identified as novel candidate biomarkers of renal disease. ConclusionsWe successfully validated a novel serum proteomic screening strategy in a spontaneous murine lupus model that highlighted potential new biomarkers. Importantly, we generated a comprehensive snapshot of the serum proteome which will enable identification of other candidates and serve as a reference for future mechanistic and therapeutic studies in lupus.

Features of the fatty acid profile of erythrocyte membranes in patients with fatty liver disease of alcoholic genesis

Introduction. Alcoholic steatosis, which is a reversible condition, is currently considered a significant risk factor for the progression of diffuse liver pathology, therefore understanding of its mechanisms at the molecular level is essential.Aim. To study the features of the fatty acid profile of erythrocyte membranes in patients with fatty liver disease of alcoholic origin for possible use of fatty acids (FAs) as biomarkers and potential therapeutic targets.Materials and methods. A total of 31 men with alcoholic fatty liver disease (AFLD) (average age of 45.1 ± 17.1 years) and 28 men of comparable age without AFLD and symptomatic pathology of internal organs were examined. The FA composition and levels of erythrocyte membranes (ER) were studied using Agilent 7000B (USA) triple quadrupole gas chromatography/mass spectrometry.Results and discussion. A higher level of a range of saturated FAs (lauric, margaric, pentadecane), monounsaturated FAs (MUFAs), which are additional factors for the progression of AFLD (palmitoleic, total monounsaturated acids), n-6/n-3 polyun-saturated FAs ratio (PUFAs), alpha-linolenic FA was detected in patients with AFL vs the control group (p = 0.00002–0.05). In contrast, the levels of arachidic and docosahexaenoic acids, total eicosapentaenoic and docosahexaenoic n-3 PUFAs, and total n-3 PUFAs were lower in patients with AFLD than in healthy men (p = 0.003–0.01), which is associated with increased ethanol induced adipose tissue lipolysis via PDE3B-AMPK axis. The use of FAs panel (C16:1;9, sum MUFA, n-6/n-3 PUFA, C22:6n3, C20:0) to distinguish patients with AFLD from healthy ones ensured high levels of sensitivity (79%), and specificity (81%) (AUC 0.808). Multidirectional associations of FA levels in erythrocyte membranes with each other and liver tests and lipid profile results were revealed.Conclusion. Thus, the features of erythrocytes membrane FAs in patients with AFLD and the potential to use them as biomarkers for differentiation of people with AFLD from healthy individuals have been identified.

Clinical and genetic characteristics of type 7 distal arthrogryposis caused by a pathogenic variant in the <i>MYH8</i> gene

Distal arthrogryposis is a group of genetically heterogeneous congenital diseases characterized by non-progressive contractures predominantly distal joints of the upper and lower extremities. 11 genes have been identified as pathogenic variants causing the occurrence of autosomal dominant and autosomal recessive types of distal arthrogryposis. Almost all products of these genes are expressed in the structures of the neuromuscular system, which makes it possible to classify distal arthrogryposis as a neuromuscular disease. Type 7 distal arthrogryposis is a rare autosomal dominant disease characterized by two main symptoms: mandibular trismus and pseudocamptodactyly, a specific symptom of limited mobility of the interphalangeal joints during hand dorsiflexion with no restriction during palmar flexion. In all patients described in the literature from different populations with type 7 distal arthrogryposis, the same pathogenic variant c.2021G>A(p.Arg674Gln) was found in the MYH8 gene, the protein product of which is one of the myosin isoforms functioning in the embryonic period and providing the formation of muscle fiber structures.The aim of the work is to describe the clinical and genetic characteristics of the first family case of type 7 distal arthrogryposis in Russian patients. The patients underwent clinical examination and electromyography. Exome sequencing after DNA isolation from the proband’s blood according to the standard method was carried out on the NextSeq 500 platform (Illumina, USA) using the pairedend reading method (2 × 75 bp). Confirmation of the pathogenicity of the identified variants was carried out using automatic Sanger sequencing.As a result of molecular genetic analysis in a father and son with clinical manifestations of type 7 distal arthrogryposis, a heterozygous c.2021G>A variant in exon 18 of the MYH8 gene, which was previously described in all patients published in the literature, was detected, leading to the replacement of p.Arg674Gln(NM_002472.2) in a protein molecule. The examined patients did not reveal focal neurological symptoms, as well as minor developmental abnomalities, pathology of internal organs, ulnar deviations, equinovarus feet deformities, vertical orientation of the talus, contractures of the hip joints, which were found with varying frequency in previously described patients with variants in the MYH8 gene. Specific clinical signs of type 7 distal arthrogryposis, combined with the presence of a major nucleotide variant, make it possible to optimize the process of molecular genetic diagnosis of this type of hereditary arthrogryposis.

Випадок ранньої інтерферонопатії у дитини в розрізі використання сучасних рекомендацій із ведення цієї патології

The article presents data from the scientific literature about the etiology, pathogenesis, and clinical manifestations of a recently discovered disease - childhood-onset STING-associated vasculopathy (SAVI), which is a genetically determined type I interferonopathy, and it clinically manifestes by a symptom complex of acral ischemia (lupus-like chilblain), interstitial lesions of the lungs and other pathologies of internal organs. SAVI more often manifests itself in the first months of a child’s life and passes under the guise of various autoimmune and infectious diseases. The article provides data on the differential diagnosis of SAVI, and emphasizes the importance of genetic testing for diagnosis. Considering the rarity of the pathology, the article includes a translation of the ACR recommendations (2021) regarding the treatment and observation of patients with interferonopathy. The article is illustrated by a description of a child with SAVI, whose diagnosis was carried out according to the principles proposed in these recommendations. The principles of follow-up of the child are described, the need for multidisciplinary management of patients with SAVI is emphasized. Current data on the prognosis and further course of the disease are provided. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

An Overview of SARS-CoV-2 Etiopathogenesis and Recent Developments in COVID-19 Vaccines.

The Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has significantly impacted the health and socioeconomic status of humans worldwide. Pulmonary infection of SARS-CoV-2 results in exorbitant viral replication and associated onset of inflammatory cytokine storm and disease pathology in various internal organs. However, the etiopathogenesis of SARS-CoV-2 infection is not fully understood. Currently, there are no targeted therapies available to cure COVID-19, and most patients are treated empirically with anti-inflammatory and/or anti-viral drugs, based on the disease symptoms. Although several types of vaccines are currently implemented to control COVID-19 and prevent viral dissemination, the emergence of new variants of SARS-CoV-2 that can evade the vaccine-induced protective immunity poses challenges to current vaccination strategies and highlights the necessity to develop better and improved vaccines. In this review, we summarize the etiopathogenesis of SARS-CoV-2 and elaborately discuss various types of vaccines and vaccination strategies, focusing on those vaccines that are currently in use worldwide to combat COVID-19 or in various stages of clinical development to use in humans.

Diagnostic Significance of Proinflammatory Cytokines in Planning Dental Implantation in Patients with General Somatic Pathologies

INTRODUCTION: The current stage of development of dental implantology permits to perform a complete dental rehabilitation even in complicated clinical situations. However, there are some difficulties which prevent achievement of a high success of implantological treatment in certain somatic pathologies that manifest in the form of systemic inflammation, and present relative contraindications for implantation. Important general somatic pathologies include chronic obstructive pulmonary disease, atherosclerosis, non-insulin-dependent diabetes mellitus, osteoporosis, etc., they are associated with the risk of acute inflammatory response of an organism to surgical implantological intervention. The risk of unpredictable complications also increases because of insufficiently wide laboratory diagnostic spectrum for planning dental implantation that includes a biochemical blood test, coagulogram, reaction to the presence of specific infections and viral diseases. This list of diagnostic data is not always sufficient for a complete prognosis of success of planned treatment in patients with a complicated general somatic or dental status. Besides, the interrelation between dental chronic diseases and general somatic pathologies which in some cases have common etiopathogenetic factors, is often not taken into account, but without the adequate diagnostic range they often remain unnoticed and lead to persistent complications in different periods after completion of treatment. Development of technologies of surgical and orthopedic dentistry permits to provide full dental care to patients even with different pathologies of organs and systems. But in this case, of importance is extended laboratory diagnostics aimed at identification of factors of chronic systemic inflammation, vascular risk, bacterial threats, for example, evaluation of some interleukins, tumor necrosis factor, C-reactive protein.
 CONCLUSION: A complex of clinical, laboratory and instrumental diagnostic methods will permit to adequately evaluate risk for treatment failure and construct a prognostic tactics of complex therapy, thereby reducing the probability for unpredictable complications in dental implantation in patients with different somatic pathologies.

Laboratory markers of multiple organ pathology in severe cases and adverse outcomes of SARS-CoV-2 infection (systematic review)

The aim of the review: to present up-to-date scientifically based information about the laboratory parameters of patients associated with severe SARS-CoV-2 infection and internal organ damage. Materials and methods: full-text publications of clinical, randomized and cohort studies, systematic reviews and meta-analyses from scientific databases PubMed, Elsevier, Scopus, Google Scholar, E-library for the period from 2019 to 2022 were analyzed. Results. Specific biomarkers were identified, including inflammatory and immunological parameters (C-reactive protein, procalcitonin, IL6), hematological (number of lymphocytes and neutrophils, NLR, D-dimer, ferritin, RDW), myocardial (troponin, creatinekinase-MB, myoglobin), hepatic (AST, ALT, total bilirubin, albumin) and characterizing lung injury (KL-6), which can be used for risk stratification, as prognostic biomarkers of adverse clinical consequences, including death in patients with COVID-19. The studies demonstrated new biomarkers of inflammatory and systemic manifestations of COVID19: procalcitonin, calprotectin and presepsin.

К ВОПРОСУ ОБ ОЦЕНКЕ КУЛЬТУРОМА БИОПТАТА ШЕЙКИ МАТКИ У ПАЦИЕНТКИ С ЦЕРВИКАЛЬНОЙ ИНТРАЭПИТЕЛИАЛЬНОЙ ДИСПЛАЗИЕЙ УМЕРЕННОЙ СТЕПЕНИ

In recent years, the role of microcenosis in the occurrence and progression of the pathology of various organs, including cervical cancer, has been actively discussed. Purpose: to study the cervical microflo-ra in a patient with moderate cervical dysplasia. Material and research methods. An extended micro-biological study of cervical mucosal cultures and cervical biopsy was performed in a patient with moderate cervical dysplasia. Cervical biopsy microcenosis was studied using a MALDI-ToF mass spectrometer (Bruker). The biocenosis of the cervical canal was studied on the basis of the polymerase chain reaction method, the Digene HPV test system test and bacteriological examination. Research results. In the biopsy specimen of the cervix, a microflora not typical for the cervical biotope was found. In particular, microorganisms were found in the tissue of the cervix, which can cause the de-velopment of pathology of the oral cavity (Streptococcus oralis, Streptococcus mitis, Streptococcus anginosus, Streptococcus sanguinis) or intestinal dysbiosis (Alloscardovia omnicolens). At the same time, these bacteria were not found in the mucous membrane of the cervical canal. Conclusion. Fur-ther research is needed to understand the causes and consequences of biocenosis differences in the altered tissue of the cervix and cervical canal.

The course of the postpartum period in cows in the presence of concomitant pathology

The decrease in productivity in cows is directly related to the pathologies of the organs of the reproductive system that occur at the end of the transit period, therefore it is important to improve the methods of diagnosis and preventive therapy of cows in this period. The purpose of the work was to establish the forms of pathologies that occur in the transit period in cows, their interrelationship and the causes that cause them in terms of seasonal dynamics. When conducting research, morphological, clinical (examination, palpation), laboratory (bacteriological studies of the uterus), and statistical (statistical reliability) methods were used. The research was conducted in the limited liability company “Milk of the Fatherland” in 2 departments where unattached housing is used. The occurrence of subinvolution of the uterus against the background of litter retention and persistent corpus luteum was established by 9.5% more in the 1st department. A 43.5% correlation of the prevalence of delayed involution with endometritis was revealed. An increase, 12.8% in January and up to 14.1 in February, of cases of subinvolution of the uterus was established, while in May the similar indicator was 5.0%. The prevalence of persistent corpus luteum was established up to 16.8%, luteal cyst – up to 1.7%, ovarian follicular cyst – 2.1%. The presence of microflora in the uterine cavity (E. coli, Ps. aeruginosa and S. aureus – 49.8% S. aureus and E. coli – 33.5%, Pr. vulgaris and E. coli – 16.7%) provoked the occurrence inflammatory processes: chronic endometritis – 10.4%, vulvovaginitis – 18.1%, cervicitis – 21.4%. Research results can be used to develop new and improve existing methods of treatment of cows with pathology of genital organs in the transit period in farms of different forms of ownership

Effects of Oyster Mushroom (Pleurotus ostreatus) on Body Weight and Pathology of Vital Organs in Pathogenic Staph Infection

Aims: Oyster mushroom is rich in secondary metabolites of pharmacological importance. This study evaluates the effect of ethanolic extract of Oyster mushroom on the vital organs of Staphylococcus aureus infected Wistar rats after seven days of administration.
 Study Design: Completely randomized design was used in the study.
 Place and Duration of Study: This study was carried out at the Microbiology, Parasitology and Ethnoveterinary medicine Unit of the Department of Animal Production and Health, Federal University of Technology, Akure, Nigeria, between March and December 2022.
 Methodology: The mushroom was processed using a cold extraction technique. A bacterial suspension of Staphylococcus aureus was inoculated via oral route into the experimental animals, which were randomly distributed into six groups of five. Group 1: normal control; group 2: positive control; group 3: negative control, inoculated but received no antimicrobial; and group 4 to 6 were inoculated, and administered with 625, 1250 and 2500 mg dose of the extract respectively. The treatment was administered for seven days, after which blood samples were cultured for the bacterial count and vital organs were analysed for pathological changes.
 Results: The colony count was significantly raised at 625 mg dose while the dose ranging from 1250 to 2500 mg yielded insignificant bacterial growth (P<0.01). The percentage weight gain was significantly lower (P<0.01) in 1250 mg extract in comparison with the negative control after 7 days complete treatment but there was no statistical variation in the 7 days post-treatment percentage weight gain and the relative organ weight (P<0.01).The histological sections showed no variation from normal controls except 625 mg liver that showed some vacuolations within the hepatocytes.
 Conclusion: The organ-body mean weight was proportionate, and the histological sections of the liver, kidney, skin, lungs, heart and spleen were indicative of no anatomical variations as compared with the normal control tissues. The beneficial effect of P. ostreatus on the vital organs was further established by the active clearing of S. aureus infection at 1250 to 2500 mg dose with no observable pathological change in the tissues. The bioactive agents inherent in P. ostreatus were effective against S. aureus infection. The vacuolations observed in the low dose liver sections unveiled the ill effect of under-dose treatment and its consequence on the liver cells. The histopathological investigations were suggestive of the safety and tolerance of P. ostreatus to the body system. Nevertheless, further studies should be carried out on its toxicological profiles.

Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.

The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.

К функциональной морфологии органов пищеварения новорожденных телят и патогенезу эшерихиоза

Despite numerous studies, the problem of escherichiosis in newborn calves remains one of the most urgent due to the extensive spread of the disease and high mortality of young animals. This paper presents results of experimental studies carried out at the FSBSI “All-Russian Veterinary Research Institute of Pathology, Pharmacology and Therapy”. The aim of the work was to conduct complex morphological studies using modern methods for a deeper understanding of escherichiosis etiology and pathogenesis. For that, pathological samples were collected from 28 1–10 day-old calves diagnosed with colibacteriosis at the initial disease stage, demonstrating pronounced clinical signs and having the terminal stage of the disease. Samples from 6 clinically healthy calves of a similar age were used as control. It was found that newborn calves at the initial stage of escherichiosis demonstrated early structural changes in the ultrastructure of mucosa cells of the rennet and small intestine, as well as in the liver parenchyma, and mild changes – in the exocrine part of the pancreas. The most profound morphofunctional changes were observed in digestive organs with apparent clinical signs of the disease. As the condition developed, the range of pathological processes expanded and involved the structural organization of the rennet, small and large intestines, liver and pancreas. At the terminal stage of escherichiosis, deep inflammatory processes occurred not only in digestive organs, but also in other systems of diseased calves. Structural changes in digestive organs had an alterative nature at the initial disease stage, whereas in case of clinically pronounced disease signs there were manifestations of catarrhal-necrotic inflammation with multiple hemorrhages in the gastrointestinal tract and parenchymal organs. Digestive organ pathology plays the leading role in formation of the clinical and morphological picture at the initial stage of escherichiosis in calves. As the disease developed, the calves demonstrated changes at molecular and subcellular levels that were detected using histochemical and ultrastructural tests.

PECULIARITIES OF THE COURSE OF THE DISEASE IN WOMEN WITH COVID-19

One of the most crucial topics at the moment is the viral infection caused by the SARS-CoV-2 coronavirus, which has acquired not only medical, but also, of course, social significance. The COVID-19 pandemic has challenged healthcare systems around the world.Pregnant women are the most vulnerable category of people, along with the elderly. Due to low immune reactivity, they are more susceptible to severe complications than others, which makes the problem of pregnancy in patients with COVID-19 a pressing issue.A successful pregnancy requires changes in the immune system of the pregnant woman to tolerate a genetically foreign fetus. These changes in the immune system, as well as in the cardiac, pulmonary, and other systems, can lead to increased susceptibility or increased morbidity and mortality due to infection during pregnancy. Considering the physiological adaptations associated with pregnancy, we found that the high metabolic demand to maintain normal intrauterine development increases the burden of oxidative stress during pregnancy. Intracellular redox changes associated with acute phase reactions at the maternal-fetal interface may be enhanced during pregnancy. Notably, mother-to-fetal transmission of SARS-CoV-2 has not been detected in most COVID-19 pregnancies. This relative absence of vertical transmission may be due to the presence of lactoferrin in the placenta, amniotic fluid, and breast secretions. However, the cytokine storm induced during COVID-19-associated pregnancies can cause severe inflammatory damage to the fetus and, if left uncontrolled, can subsequently lead to autism spectrum disorders and brain developmental abnormalities in newborns. Given this serious health threat to a child's growth and development, preventing COVID-19 during pregnancy should be a priority.We aimed to study risk factors and assess the course of pregnancy in women with COVID-19.The study was carried out within the framework of the research work "Clinical and pathogenetic substantiation of differentiated treatment of combined pathology of internal organs" (№0122U002209).

Breast Carcinoma and Tuberculosis in Axillary Lymph Nodes: A Case Report

The coexistence of tuberculosis with axillary lymph node metastases in breast carcinoma is rare. Axillary lymph node metastasis is the most important factor in the staging of breast carcinoma, this can mimic or complicate the staging of a malignant disease. Dual organ pathology can lead to interpretation difficulties and inappropriate treatment of tuberculosis as well as breast carcinoma. We report an observation of infiltrating carcinoma of the non-specific type of the breast in woman aged 39, where tuberculosis was found in the axillary lymph nodes in addition to metastases. The possible and simultaneous occurrence of breast carcinoma and tuberculosis should be mentioned in order to avoid difficulties of interpretation and allow adequate management of axillary tuberculous lymphadenitis and breast carcinoma.

Сердечные тропонины: современное представление о клиническом и прогностическом значении в многопрофильном стационаре

The increase of patients with elevated cardiac troponins in blood without signs of acute coronary syndrome in recent years, associated, among other reasons with the pandemic of coronavirus infection, has made differential diagnosis difficult for physicians of multidisciplinary hospitals. Aim of the study: to investigate the clinical and prognostic significance of elevated cardiac troponins associated with non-coronarogenic causes, including in the COVID-19 pandemic conditions. Materials and methods: a search of 57 literature sources from eLIBRARY, PubMed, Web of Science, Scopus, Google Scholar, and freely available Yandex and Google databases was performed. The results of the literature review showed that the use of highly sensitive cardiac troponins is relevant for clinical evaluation of the course and differential diagnosis of heart diseases (coronary and non-coronary) and other internal organs pathology, but the accuracy of the troponin test, combined with its nonspecificity, requires a cautious approach to the interpretation of the results. Also isolated elevation of cardiac troponins does not indicate the mechanism of myocardial damage and is not an indication for patients transfer to intensive care units or vascular centers. Routine use of troponin tests makes it difficult to make true diagnosis for patients in a multidisciplinary hospital. Many studies have shown that elevated troponin levels not associated with acute coronary syndrome have a negative prognostic value, but when the coronary event is excluded, elevated troponin levels should not be ignored; it is necessary to look for the cause of such changes. The integration of cardiac troponins in predicting the risk of occurrence, progression, and complications of various diseases is a promising area for further research.

Role of Defibrotide in the Prevention of Murine Model Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vascular endothelial cells are entirely exposed and damaged during the pathogenesis of acute GVHD. Defibrotide is a mixture of single-stranded oligonucleotides that has several pharmacological effects that contribute to its endothelial protective properties. B10.BR mice were conditioned followed by the infusion of donor C57BL/6J T-cell depleted (TCD) bone marrow cells with or without splenocytes. Animals were either treated with defibrotide or appropriate controls daily for the first week and then three times per week thereafter. Allogeneic defibrotide-treated recipients demonstrated significantly better survival with reduced clinical GVHD. Significantly reduced organ pathology in the gut was associated with significantly decreased T-cell infiltration in the ileum and colon on day +28. Serum cytokine analysis revealed significantly reduced level of TNF and IL-6 at day +7 and TNF at day +28 in allogeneic defibrotide treated recipients. Significantly reduced levels of ICAM-1, Angiopoietin-2 in serum and reduced VCAM-1 and HCAM in the ileum and colon of allogeneic defibrotide-treated recipients were observed. Improved survival was seen in the GVL model (C3H.SW into C57BL/6J mice with C1498-luc). Defibrotide treatment through its anti-inflammatory and endothelial-protective effects reduces the severity of acute GVHD, while not impairing GVL activity.

Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse.

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.

Simultaneous interventions in surgical gastroenterology and herniology: prediction and prevention of complications

The aim of the study - to improve the results of simultaneous surgical treatment of patients with large ventral hernias and incisional hernias W3 and concomitant surgical pathology of the abdominal organs. Material and methods. The article analyzes the results of surgical treatment of 450 patients with primary and postoperative hernias of the abdominal wall. 95 (21.1%) patients were urgently operated on. In 76 (16.9%) patients with large ventral and incisional W3 hernias, posterior separation hernioplasty was performed using TAP technology. In the presence of concomitant surgical pathology of the abdominal organs, simultaneous surgical interventions were performed. Results. In sublay and IPOM groups, 14 (3.7%) patients underwent laparoscopic sleeve resection of the stomach, 16 (4.3%) patients - laparoscopic cholecystectomy, and 4 (1.1%) patients -TAPP hernioplasty. In TAR group, 9 (11.8%) patients underwent open cholecystectomy, 12 (15.8%) - transverse abdominoplasty, 3 (3.9%) - open sleeve resection of the stomach, 2 (2.6%) - closure of the colostomy. The average duration of pain in the postoperative period was 4.5±0.9 days. The average duration of hospitalization was 9.7±1.1 days. In the postoperative period, 2 patients developed surgical site infection. There was no mortality. Conclusions. Modern simultaneous interventions in surgical gastroenterology and herniology with risk stratification of specific and nonspecific complications are an actuale social, medical and economic problem. An individual and differentiated approach to choice of simultaneous surgical intervention method taking into surgical and anesthetic risks and patients comorbidity, can reduce the percentage of postoperative complications and improve patient’s life quality.