Unfavorable Course Research Articles

Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.

Patients with lissencephaly typically present with severe psychomotor retardation and drug-resistant seizures. The aim of this study was to characterize the epileptic phenotype in a genotypically and radiologically well-defined patient cohort and to evaluate the response to antiseizure medication (ASM). Therefore, we retrospectively evaluated 47 patients of five genetic forms (LIS1/PAFAH1B1, DCX, DYNC1H1, TUBA1A, TUBG1) using family questionnaires, standardized neuropediatric assessments, and patients' medical reports. All but two patients were diagnosed with epilepsy. Median age at seizure onset was 6 months (range: 2.1-42.0), starting with epileptic spasms in 70%. Standard treatment protocols with hormonal therapy (ACTH or corticosteroids) and/or vigabatrin were the most effective approach for epileptic spasms, leading to seizure control in 47%. Seizures later in the disease course were most effectively treated with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, resulting in seizure freedom in 20%. Regarding psychomotor development, lissencephaly patients presenting without epileptic spasms were significantly more likely to reach various developmental milestones compared to patients with spasms. Classic lissencephaly is highly associated with drug-resistant epilepsy starting with epileptic spasms in most patients. The standard treatment protocols for infantile epileptic spasms syndrome lead to freedom from seizures in around half of the patients. Due to the association of epileptic spasms with an unfavorable course of psychomotor development, early and reliable diagnosis and treatment of spasms should be pursued. For epilepsies occurring later in childhood, ASM with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, appears to be most effective.

Dynamics of Cognitive Impairment in MCI Patients over a Three-Year Period: The Informative Role of Blood Biomarkers, Neuroimaging, and Genetic Factors.

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered.

Long-term courses of alcohol dependence

Descriptions of long-term histories of alcohol dependence provide insight into the etiology, prevention and care. Report of empirical findings about the development into and remission from alcohol dependence. Narrative literature review, analysis of findings from cohort studies in the general population. Risk factors provide the opportunity to estimate increased probabilities of developing an alcohol dependence. Adolescents disclosed symptoms of alcohol dependence within 8 years after the first alcohol consumption. Alcohol dependence is related to alife expectancy 17.6 years fewer than in the general population. Data of ageneral population sample revealed arisk of early death 2.8times higher than among people without mental disorders. The severity of alcohol dependence was shown to be a predictor of premature death. Nicotine dependence can add to the shortening of life in addition to alcohol dependence. Among the alcohol dependent residents in ageneral population sample, 90.2% did not have utilized detoxification treatment that included motivational treatment and 78.4% did not have utilized standard detoxification treatment in apsychiatric treatment facility. Remission without formal help has been proven. It is the main route of remission. To reduce unfavorable courses of alcohol dependence, prevention and treatment should be focused more on the needs in the general population. In psychiatric and other medical routine care, screening and an appropriate brief intervention should be carried out.

Metabolic Profiles of the Gut Microbiota in Patients with Different Stages of Metabolism Dysfunction-Associated Fatty Liver Disease

Aim: to study the metabolic activity of the intestinal microbiota depending on the stage of metabolic dysfunction-associated fatty liver disease (MAFLD). Materials and methods. The study included 85 patients with MAFLD (27 patients with steatosis without steatohepatitis and fibrosis, 42 patients with steatohepatitis, 16 patients with cirrhosis as an outcome of MAFLD, Child — Pugh class A–B) and 20 healthy people who formed the control group. The level and spectrum of short-chain fatty acids (SCFA) were determined by gas-liquid chromatography. Results. It was found that patients with MAFLD at the stage of steatosis and cirrhosis of the liver have unidirectional changes in the metabolic activity of the intestinal microbiota. We established a decrease in the absolute concentrations of SCFA — their total content, the level of acetate, propionate, butyrate, a decrease in the level of isoacids. The SCFA profiles showed an increase in the proportion of acetate and a decrease in propionate and butyrate. Moreover, changes in the named parameters of SCFAs are aggravated with progression to liver cirrhosis. At the stage of steatohepatitis, we identified two subgroups of patients with different levels of metabolic activity of the microbiota. Patients whose microbiota metabolism for SCFA production was high had correspondingly elevated SCFA levels. And, on the contrary, patients in whom the metabolic activity of the microbiota was reduced were characterized by a steady decrease in SCFAs and disease progression to liver cirrhosis. In the study, we showed an inverse correlation between the calculated prognostic indices of NFS and FIB-4, elastography values with the total level of SCFA, the level of acetate, propionate, butyrate. Thus, a decrease in the content of SCFA for patients with MAFLD can be considered as a prognostic marker of an unfavorable course of liver disease.

Роль субъективного возраста в системе психологических факторов течения болезни у мужчин с раком предстательной железы. Часть I. Субъективный возраст и качество жизни у мужчин с раком предстательной железы

<p><strong>Relevance.</strong> Prostate cancer remains one of the major public health problems worldwide, as it is accompanied by high rates of morbidity and mortality. Purpose. The work is devoted to the study of the role of subjective age in the system of psychological factors of the course of the disease in men with prostate cancer; in this part of the work, attention is focused on the relationship between subjective age and quality of life. <strong>Materials and methods</strong>. The study involved 127 men aged 53 to 85 years (М=68; Ме=69; SD=10,27) diagnosed with prostate cancer (stage I of the disease – 16 men; stage II – 64; stage III – 13; IV – 34; favorable course of the disease – 40 people, unfavorable - 61). In addition to socio-demographic data, subjective age was studied (B. Barak questionnaire in adaptation by E.A. Sergienko, 2011), quality of life – subjective health assessments (SF-36 questionnaire in adaptation by K.G. Gurevich, E.G. Fabrikant, 2008). This work consists of two parts describing the role of subjective age in the system of psychological factors in men with prostate cancer. Part I of the article is devoted to the analysis of the role of subjective age and quality of life assessments. Three subgroups were identified according to estimates of subjective age: those who feel younger than their passport age (80 people), adequate to their age (44 people) and older (3 people). <strong>Results and conclusions</strong>. The analysis of men with different perceptions of subjective age with a favorable and unfavorable course of the disease was carried out. It is shown that men who feel younger concentrate on the physical aspects of health and their own vitality, fearing for the level of their own activity and compliance with gender functioning, regardless of the prosperous/dysfunctional course of the disease.</p>

Clinical and economic assessment of using topical bacterial lysate Imudon® for the treatment and prevention of acute upper respiratory tract infections in children

Objective: pharmacoeconomic analysis of the feasibility of using topical bacterial lysate Imudon® for the treatment and prevention of acute upper respiratory tract infections in the pediatric population in comparison with other medicines belonging to the class of topical antiseptics.Material and methods. For the population calculated on the basis of Rosstat data, taking into account the Russian clinical recommendations "Acute respiratory viral infection (ARVI)" and "Acute tonsillitis and pharyngitis (acute tonsillopharyngitis)", the direct medical costs of medical care were determined. The cost of basic therapy of 1 case of acute respiratory infection (ARI) with symptoms of pharyngitis was calculated for two variants of clinical course: favorable (when ARI proceeds without complications and the patient does not need to be prescribed antibacterial drugs), and unfavorable (when confirmed bacterial infection joins and antibiotics are required). The indirect costs of child care are associated with lost gross domestic product (GDP). In estimating the GDP shortfall, it was assumed that the parent does not contribute to the country’s GDP during the entire childcare period.Results. GDP per capita for 2022 amounted to 2853.13 rubles per day. Thus, with a favorable course of the disease, indirect costs will be 19,972 rubles, and with an unfavorable course – 39,944 rubles. The total costs of the healthcare system and the state for 1 ARI patient are 32,192 rubles in case of favorable course and 71,644 rubles in case of unfavorable course. Imudon® administration allows reducing direct costs of parents for purchase of medicines for treatment of 1 ARI case by 23.6% compared to the therapeutic strategy associated with the use of local antiseptics.Conclusion. For the first time in Russian economic conditions, the use of Imudon® for the treatment and prevention of acute upper respiratory tract infections in children was evaluated. Its use from the first ARI symptoms allows refusing the use of local antiseptics, shortens the duration of the disease symptoms, and reduces the need for antibiotics, i.e. is feasibleable compared to local antiseptics.

Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.

Criteria for predicting the development of recurrent peripheral nerve sheas tumors

Peripheral nerve sheaths tumors (PNST) account for about 8 % of all nervous system cancers. The relapse rate ranges from 17.3 to 26.4 %, showing an upward trend. The causes and provoking factors for the development of relapses of PNST have not been fully studied. Purpose of the study: to establish criteria for predicting recurrence of PNST. Material and Methods. The study included 122 patients who were treated at the Department of Spine and Peripheral Nerve Surgery of A.I. Polenov Russian Research Neurosurgical Institute from 2009 to 2021. Among them, there were 87 (71.3 %) patients with primary PNST and 35 (28.7 %) patients with recurrent PNST. All patients underwent MRI and ENMG both before and after surgery. An immunohistochemical study of Ki67 and SO X10 markers was performed. Results. The majority of relapses occured within 1 year after surgery. In cases with radical removal of PNST, the risk of relapse was: 28.6 % for schwannomas 28.6 %, 37.1 % for neurofibromas and 34.3 % for MP NST 34.3 % (p≥0.05). The risk of developing relapse of PNST was 2.9 times higher in patients aged ≥49 years than in patients aged ≤48 years (p<0.004). The larger the initial size of the tumor, the higher the risk of relapse in the late postoperative period. The risk of developing relapse of MP NST was 8.79 times higher in patients with tumor size of greater than 11.5 cm than in patients with smaller tumor size (p<0.02). The of Ki67 level above 4.85 % in schwannomas and above 5.17 % in neurofibromas can predict relapse of PNST (p<0.05). Loss of SO X10 protein expression was associated with an increase in histological anaplasia of the tumor, which causes a high risk of relapse and an unfavorable clinical course of the disease. Conclusion. Despite radical (total) resection of PNST, the risk of relapse remains high. The pathological type of tumor, its size, levels of SO X10 and Ki67 markers, patient’s age, degree of preoperative neurological deficit and extent of surgery are significant criteria for predicting the development of relapse of PNST.

Features of underground flow formation to the Golovesnya river (Desna basin) during the dry period 2007-2021

Purpose. To analyze the peculiarities of the dynamics of underground flow on the catchment of the Golovesnya River, a right-bank tributary of the Desna River, during the dry period of 2007-2021 in comparison with the period of 1960-1985 - before the beginning of noticeable climatic changes. Methods. The hydrodynamic finite-difference method of calculating the specific consumption of groundwater based on the data of routine observations of the levels of groundwater and surface water, the hydrodynamic method of calculating the components of the groundwater balance. Results. The specific flow of groundwater to the Golovesnya River was calculated based on the data of observations for 2007-2021; the share of groundwater flow in the total flow of the river was determined, changes in the dynamics of infiltration nutrition and the inflow of groundwater to the river were revealed, which can be associated with the sign of the charge of the static electric field of the surface layer of the atmosphere, an increase in air temperature, and an increase in the volume of moisture retention in the aeration zone after reducing GWT. Underground flow to the river largely compensates for the losses and stabilizes the river flow in low-water years and during prolonged hydrological drought. Important factors in the regulation of the groundwater regime in low-water periods (in addition to precipitation) are the level and flow of water in the river, as well as the loss of moisture due to the saturation of the aeration zone, and therefore, the lithological and granulometric composition of this zone. Losses in the aeration zone are also an important regulatory factor of balance and river flow in the scale of the Desna River catchment. The largest volumes of underground runoff to the Golovesnya River for 2007-2021 were set for the multi-water year 2016, the smallest - for 2021. By 2016, the chronological graphs show clearer seasonal patterns: repeatability of underground flow fluctuations in the spring and autumn seasons; opposite flow fluctuations in winter and spring and a relatively stable summer flow; typical for autumn are maximum, and for summer always minimum values ​​of reserves and infiltration recharge of groundwater. In the abundant water year of 2016, infiltration recharge and groundwater reserves during autumn and winter sharply decrease and acquire negative values ​​due to a significant decrease in GWT in the previous period, an unfavorable course of temperature and precipitation distribution, and increased outflow to the river. In 2017-2021, the seasonal differences in the recharge of the river with groundwater are almost equalized: the role of recharge increases during the summer period, and decreases during the spring and autumn seasons. The role of the condensation mechanism of moisture transfer in the aeration zone is increasing. During the summer, the lateral inflow of groundwater to the river was the highest in 2016-2018. Conclusions. Calculations and analysis of the dynamics of infiltration feeding and groundwater flow to the Golovesnya River have been performed. Changes in groundwater supply and discharge, especially in the period after 2015, have been identified, which can be interpreted as the consequences of adverse weather and climate conditions in 2014-2015. In 2018-2021, there was a decrease in groundwater and surface water resources, which corresponds to signs of hydrological drought.

ASSESSMENT OF HEALTH-RELEVANT QUALITY OF LIFE IN THE CONTEXT OF THE MEDICAL AND SOCIAL PROFILE OF WOMEN WITH COMPLICATED PREGNANCIES

In modern Russia, there is a decline in the birth rate, a decline in women's reproductive health, and a high rate of complicated pregnancy and childbirth. The causes of unfavorable course and outcome of pregnancy are multifactorial. The contribution of medical factors to the course of the gestational process and the condition of the newborn is often not determinant in the course and outcome of pregnancy. One of the factors influencing the course of pregnancy is health-relevant quality of life. The aim of the study was to analyze the influence of certain characteristics of the medical and social profile on the health-relevant quality of life of pregnant women with complicated pregnancy. Materials and Methods. 153 pregnant women with complicated pregnancy were included in the study. Cohort one-stage sociological study of quality of life was realized by questionnaire survey method. The study of health-relevant quality of life of pregnant women with complicated pregnancy was conducted using the WHOQOL-100 questionnaire (WHO QOL-100). Results. When assessing the quality of life of pregnant women, there is a decrease in the average values of quality of life indicators in the spheres and subspheres of the questionnaire, determined by the somatic condition of respondents. A statistically significant dependence of the decrease in the mean values of the quality of life indicators of respondents in the age group of 30-39 years compared to respondents aged 20-29 years has been established. The evidence of the influence of the level of education on the quality of life of women with pathologic course of pregnancy is presented. In a comparative analysis of the quality of life of respondents whose professional activity is not associated with physical exertion and respondents who perform physical labor of varying degrees of severity, the greatest decrease in the average quality of life indicators is noted in the group of respondents engaged in heavy physical labor. There are higher quality of life indicators of respondents who are officially married. Conclusions. The conducted study provides evidence of somatic and social determinacy of health-relevant quality of life in pregnant women with complicated pregnancy. The established limitations of the quality of life allow objectifying personalized medical and social assistance to pregnant women, aimed at improving their quality of life and pregnancy outcome.

Эволюция транспупиллярной лазерной коагуляции сетчатки в лечении активной ретинопатии недоношенных: от режима одиночного импульса до навигационного сопровождения

Abstract Evolution of transpupillary laser coagulation of the retina in the treatment of active retinopathy of prematurity: from single pulse mode to navigational support A.V. Tereshchenko, I.G. Trifanenkova, Yu.A. Sidorova, V.V. Firsova, V.V. Shaulov S. Fyodorov Eye Microsurgery Federal State Institution, Kaluga branch, Kaluga, Russian Federation K.E. Tsiolkovski Kaluga State University, Kaluga, Russian Federation Purpose. To present the development stages and results of 18 years of experience in laser technologies application for the treatment of premature infants with active ROP in the Kaluga branch of S. Fyodorov Eye Microsurgery Federal State Institution. Material and methods. Transpupillary laser coagulation of the retina (LCR) was performed in 1583 children (2537 eyes) with active ROP for the period from 2004 to 2021. LCR was carried out with various stationary laser ophthalmocoagulators. Stages 2 and 3 of active ROP with an unfavorable disease course, stage of early clinical manifestations, manifestation of aggressive posterior ROP were indications for laser treatment. Results. Transpupillary LCR began to be performed for children with active ROP with a stationary ophthalmic coagulator for the first time in Kaluga branch of the S. Fyodorov Eye Microsurgery in 2004. The technology of patterned LCR in active ROP was applied for the first time at domestic and international clinical practice, in the Kaluga branch of Eye Microsurgery in 2009. Pattern LCR began to be performed on the Integre Pro Scan device in 2016. Pattern with the most dense and uniform arrangement of laser applications – hexagonal – was identified. In 2021 transpupillary LCR of the avascular zone of the retina was performed in automatic mode with navigation support on the Navilas 577s laser system. It was possible to perform LCR of the avascular zone of the retina up to the dentate line in all cases. Regression of disease was achieved in 100% of cases. Conclusion. Evolution of laser technologies and the experience of their use demonstrate the high efficacy, safety and predictability of the results of laser treatment of active ROP. Modern pattern laser techniques are highly effective, safe, dosed and tissue-saving, which can serve as the basis for standardization of retinal laser coagulation technology in the treatment of active ROP. Key words: retinopathy of prematurity, unfavorable type of course, laser coagulation of the retina, hexagonal pattern, navigation system

Features of post-surgical menopause with concomitant primary hypothyroidism: A prospective single-stage clinical study

Background. In recent decades, the frequency of surgical interventions on reproductive system organs has been steadily increasing. In gynecological practice, preference is given to minimally invasive surgery and precision treatments, especially involving ovaries. Despite the modern approach, it is not always possible to preserve this endocrine organ, which leads to post-surgical menopause (PSM). The relatively high incidence of total hysterectomy-associated PSM and primary hypothyroidism in late reproductive age often leads to their combination. Clinical manifestations aggravating each other form an unfavorable vicious circle. Aim. To study the features of the PSM course with concomitant primary hypothyroidism. Materials and methods. A prospective clinical study included 130 women aged 45 to 55 years with a history of PSM. The main group consisted of 70 patients with PSM with subclinical primary hypothyroidism. A control group included 60 PSM patients without thyroid disorders. We assessed the effect of hypothyroidism on the PSM course by comparing several indicators in the main and control groups. Results. It was found that in the main group patients, severe 26.5% and moderate 38.8% menopausal syndrome prevailed, while in the control group patients, such forms were twice as common. In the women of the main group, the levels of triglycerides were higher than those in the control group by 1.3 times (2.6±0.86 mmol/L and 1.43±0.33 mmol/L, respectively). The total serum alkaline phosphatase activity in patients in the study groups was 29.8% higher than in healthy women. Conclusion. It can be concluded that the severity of menopausal disorders depends on the thyroid status, with more severe in patients of the main group with hypothyroidism. In addition, in patients of the main group with hypothyroidism, dyslipidemia is more pronounced, which predisposes them to severe diseases in the future, in particular cardiovascular disorders, the unfavorable course of metabolic syndrome, and the development of postmenopausal osteoporosis.

Granulomatosis with polyangiitis, complicated by ocular adnexa lesion and vascular changes in retina and choroid (literature review with a clinical case)

Granulomatosis with polyangiitis (GPA) is manifested as ocular pathology in almost a third of patients, which can either be detected at the onset of the disease or occur in the late stages. The pathological process involves the orbit, sclera, episclera, cornea, conjunctiva, eyelids, nasolacrimal system, optic nerve, retina and choroid. Lesion of eye and its surrounding structures determines the severity of the pathological process, the patient’s quality of life and prognosis. The article presents a clinical case of a 38-year-old man with an unfavorable course of GPA, lesion to upper and lower respiratory tract, kidneys, and musculoskeletal system. The authors consider ocular manifestations in the context of a systemic disease. An ophthalmological examination of the patient revealed changes in sclera and choroid, which had not previously been described in detail in the literature. The patient underwent cataract phacoemulsification in the right eye with implantation of a posterior chamber intraocular lens. The dynamics of clinical manifestations of eye lesion in the near future is positive, but in the long term it remains doubtful due to pronounced changes in the orbit and adnexa of the eye against the background of ongoing small vessels vasculitis. Early consultation with an ophthalmologist and optical coherence tomography in patients with GPA are necessary at any stage of the disease. The clinical case is presented with consideration to the CARE 2021 recommendations.

Human leukocyte antigen (HLA) class I expression on Hodgkin-Reed-Sternberg cells is an EBV-independent major determinant of microenvironment composition in classic Hodgkin lymphoma.

Hodgkin-Reed-Sternberg cells (HRSCs) in classic Hodgkin Lymphoma (HL) frequently lack expression of human leukocyte antigen class I (HLA-I), considered to hamper activation of cytotoxic T cells in the tumor microenvironment (TME). Here, we demonstrate HLA-I expression on HRSCs to be a strong determinant of TME composition whereas expression of HLA-II was associated with only minor differential gene expression in the TME. In HLA-I-positive HL the HRSC content and expression of CCL17/TARC in HRSCs are low, independent of the presence of Epstein-Barr virus in HRSCs. Additionally, HLA-I-positive HL shows a high content of CD8+ cytotoxic T cells. However, an increased expression of the inhibitory immune checkpoint LAG3 on CD8+ T cells in close proximity to HRSCs is observed. Suggesting interference with cytotoxic activity, we observed an absence of clonally expanded T cells in the TME. While HLA-I-positive HL is not associated with an unfavorable clinical course in our cohorts, they share features with the recently described H2 subtype of HL. Given the major differences in TME composition, immune checkpoint inhibitors may differ in their mechanism of action in HLA-I-positive compared to HLA-I-negative HL.

The German COVID-19 rheumatism register

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic in December 2019 there was no available evidence regarding the management of immunosuppressive or immunomodulatory treatment and the potential outcomes of severe acute respiratory syndrome coronavirus type2 (SARS-CoV-2) infections in inflammatory rheumatic diseases (IRD). As aresult, the Justus Liebig University of Giessen, Germany, in collaboration with the German Society for Rheumatology, established the German COVID-19 register ( www.covid19-rheuma.de ). The COVID-19 register enabled for the first time a systematic documentation and evaluation of viral infections in patients with IRD. The data collection started as early as March 2020. Currently, the register is one of the largest global registers in the field of COVID-19 and IRD. As of 18 December 2023 the register has recorded more than 7100 cases. The first scientific findings on SARS-CoV‑2 infections in IRD patients were generated from the register in 2020, showing an association between disease activity of IRD, certain comorbidities, such as cardiovascular diseases and treatment with rituximab, with an unfavorable course. The contents and construction of the database of the register were designed at the conception to allow collaboration and data exchange with other national and international registers (e.g., EULAR COVID-19 register, COVID-19 global rheumatology alliance and the Lean European open survey on SARS-CoV‑2 infected patients). In addition, other registers and surveys were initiated. A vaccination register documents the tolerability and possible adverse reactions to COVID-19 vaccination in IRD patients. The data resulted in numerous publications and formed the basis for national and international recommendations for action in the care and vaccination of IRD patients during the COVID-19 pandemic. In summary, the German COVID-19 register has made asignificant contribution to the understanding of the course of COVID-19 in IRD patients and has facilitated international collaboration for abetter understanding of COVID-19 and IRD.

Association of adipose tissue mediators with the development of cancer in patients with metabolic syndrome

The aim of the study was to summarize the available data on the relationship between adipose tissue mediators and cancer in patients with metabolic syndrome. Material and methods. A literature search was conducted using the PubMed and eliBRARY databases. Of the 400 articles published over the past 20 years, 58 studies were included in the review. Results. There is evidence of an unfavorable course of cancer in patients with metabolic syndrome that is explained by the presence of common pathogenetic pathways. In this review, special attention is paid to adipose tissue mediators that regulate the course of inflammation. The involvement of adipose tissue mediators in the pathogenesis of cancer is discussed. The relationship between adipokines of adipose tissue and the effects of specialized pro-resolving mediators (SpRM), which are metabolites of polyunsaturated fatty acids (resolvins, protectins and maresins), are considered. the associations of mediators that regulate the intensity of inflammation with the metabolic syndrome and cancer are discussed. Conclusion. Further studies will contribute to a better understanding of the relationship between metabolic syndrome and cancer and the search for adequate predictive markers to select the most effective drug strategy for correcting metabolic syndrome.

Placental alkaline phosphatase is a biocatalyst of metabolic dysfunctions of the placenta

The parameters of the enzyme involved in biologically important reactions occurring in an open thermodynamic system — the body of a pregnant woman during the gestational period — were studied. The role of an unfavorable premorbid back ground has been established: infectious diseases, repeated exacerbations of chronic inflammatory processes during prolongation of pregnancy, risk factors for perinatal complications, which causes certain morphofunctional changes in the placenta, form ing placental insufficiency. Pregnant women associated with diseases of the genitouri nary system are more often susceptible to infection. Ultrasound examinations made as part of screening the physiology of the system: mother — placenta — fetus, revealed changes in the structure of the placenta, which indicated a disruption in the relationship between the nascent embryo and the mother’s body, and ultimately manifested itself as violations of compensatory and adaptive mechanisms in the placenta, more pronounced in the sample, burdened by the presence of chronic foci of infection. The dependence of disturbances in the functional ability of the placenta on the level of the enzyme — thermostable alkaline phosphatase specific for it — was revealed. At the same time, a change in the activity of this enzyme was observed, which determined the compensatory capabilities of the provisional organ. In patients with an increased infectious index and placental dysfunction, unstable values of a specific placental enzyme are observed, as evidenced by an unfavorable course of pregnancy, accompanied by the threat of miscar riage and premature birth. These disorders occurred during prolongation of pregnancy and during the process of delivery. A significant decrease in the activity of placental alkaline phosphatase and a decrease in its relationship to alkaline phosphatase were es tablished. The worst indicators reflecting the intrauterine development of the fetus were observed in the sample with placental dysfunction and the risk of infectious complica tions, which was associated with delayed fetal development, and the birth of children with a combination of signs of intrauterine suf fering and hypoxia.

Clinical and diagnostic substantiation for computed tomography of internal organs in acute lung injury in intensive care unit

Objective. To conduct a clinical and diagnostic substantiation of computed tomography (CT) of internal organs in acute lung injury (ALI) in intensive care.Methods. 96 patients of the intensive care unit of the Clinical hospital No 1(Smolensk) were examined. CT scans of the lungs, liver, and brain were performed using a tomograph GE Revolution EVO64. Clinical structure of the patients: 49 – with pneumonia, 15 – septic condition, 12 – Inhalation of toxic substances, 8 – aspiration of toxic liquids, 3 – aspiration of disosmolar liquids, 3 – disseminated intravascular coagulation, 3 – pulmonary contusion, 3 – shock condition. Statistical processing of the results was carried out in the Statistica 6.0 program.Results. Of the 15 patients without changes of the lungs on CT scan, in 12 patients’ attenuation value of liver parenchyma was 14–28HU, brain attenuation value was 24–30HU. In patients with established changes in lung tissue (n=81), the density of liver tissue less than 54HU, brain density less than 32HU in 80.2 % of cases allowed us to predict an unfavorable course of ALI. 10 deaths were recorded, 6 patients were in critical condition for a long period of time. Treatment of hemostasis disorders, normalization of water-electrolyte homeostasis, elimination of hypoxemia, prescription of hepatoprotective, antibacterial, detoxification therapy helped to avoid an unfavorable outcome.Conclusions. 1. It is recommended to consider of criteria for an unfavorable course in patients with acute lung injury the attenuation value of liver parenchyma less than 54HU and brain tissue attenuation value less than 32HU on CT (r=0.969 and r=0.988). 2. CT scan of the liver and brain allows the resuscitator to correct therapy and decide whether it is necessary to involve other specialists. 3. Diagnostic and prognostic significance of a complex CT scan in patients with acute lung injury, at the patient’s admitting AUROC 0.998; CI 0.901–0.999; at follow-up AUROC 0.835; CI 0.822–0.847.

Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency.

Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) - if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the 'impending HTN-E' group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. 'Impending HMOD' means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.

Prognostic value of p14ARF expression in diffuse large B cell lymphoma

The p14ARF-Hdm2-p53 signaling pathway targets tumor growth suppression, inhibits clonal proliferation, and maintains genome stability. It is inactivated in most human malignancies. The p14ARF protein is one of the main participants in the cascade. The aim of the study was to determine the prognostic value of the number of p14ARF-expressing tumor cells in biopsies of patients with diffuse large B cell lymphoma (DLBCL). Material and methods. The formalin-fixed paraffin embedded samples of tumor tissue of 104 patients with newly diagnosed DLBCL were included to the study. The relative number of cells expressing p14ARF was determined by immunohistochemical and morphometric methods. Differences in the content of p14ARF-positive tumor cells between groups of patients divided according to clinical and laboratory parameters were determined using the Mann–Whitney U test. Prediction of an unfavorable response to therapy was carried out using binary logistic regression with calculation of the odds ratio and 95 % confidence interval; variables were selected using Wald backward elimination method. The risk of an event occurring was calculated using Cox regression analysis. Results. The content of p14ARF-positive cells is higher in tumor biopsies of patients with high and high-intermediate risk according to the international prognostic index than in patients with low and lowintermediate risk. A relationship between an increase in the number of p14ARF-positive tumor cells, the absence of a complete response to first-line R-CHOP therapy, and an increased risk of death in patients with DLBCL has been established. Conclusions. The studied marker p14ARF can be used as an additional morphological predictor of the unfavorable course of DLBCL.