Introduction. Worldwide, more than 182 million cases of COVID-19 and more than 3.9 million deaths have been confi rmed since the virus was fi rst identifi ed. Advanced age and some comorbid conditions, such as diabetes and cardiovascular diseases, are considered risk factors for the adverse course of the discussed pathology. In recent years, several reports have been published about the results of the pathological examination of patients with COVID-19. Most often, in fatal cases, diff use alveolar damage is described, which is characterized by intraalveolar edema, the appearance of “hyaline” membranes and the proliferation of pneumocytes and fi broblasts. However, the nature of the damage caused by SARS-CoV-2 remains unclear. The study of pathomorphological changes in severe fatal cases of COVID-19 is important for a better understanding of pathogenetic mechanisms of the development of pulmonary complications and the development of new eff ective methods of antiviral treatment. The aim of the current study is to evaluate the gross and microscopic fi ndings in COVID-19 patients’ autopsy to investigate the clinicopathologic basis for adverse outcomes with a fatal course of the disease. Methods. A retrospective analysis of 1036 consecutive autopsies associated with COVID-19 in 2020 was conducted based on Lviv Regional Offi ce for Autopsy and Lviv Railway Clinical Hospital. The diagnosis of COVID-19 was confi rmed by clinical signs of viral pneumonia, nasopharyngeal smear analysis, and radiological changes. A statistical study was performed with IBM SPSS Statistics 24.0. Results. The majority (72.4%) were elderly (60+) males (54.1±1.5%) and females (45.9±1.5%), with an age range from 19 to 93 years (mean age 66.9 ± 0.4 years). All examined patients had pneumonia, which was detected during a clinical examination with CT diagnosis and confi rmed at autopsy. The acute exudative phase of pneumonia was diagnosed in 18.5±1.2% of cases, proliferative phase – in 18.5±1.2%, and fi brotic phase – in 5.9±0.7%. And in 53.5±1.5% of cases, signs of progressive fi brosis associated with exudative lesions prevailed. COVID-19 was the single original cause of death in 88.7±1.0% of cases. The following were identifi ed in the lungs: typical virus-induced changes in epithelial cells of the trachea, bronchi, bronchioles and alveoli (100%, n=1036); diff erent phases of diff use alveolar damage in the majority of cases (96.5±0.6%); manifestations of innate immunity were described; pathological changes in the microvasculature (large vessel thrombi were detected in 37.9±1.5%). Conclusion. Our study results prove the importance of pathological examination of tissues during autopsies to determine the pathophysiological mechanisms and underlying causes of death of patients with COVID-19. Keywords: COVID-19, SARS-CoV-2, diff use alveolar damage, vessel thrombi, elderly males.

На сьогодні не до кінця встановлені всі фактори, що визначають швидкість і характер розвитку й прогресування діабетичної ретинопатії (ДР) при цукровому діабеті 2-го типу (ЦД2). Актуальною є розробка інформативних методів діагностики й прогнозування перебігу порушення інтраретинальної мікроциркуляції при ДР. Важливим чинником розвитку геморагій сітківки ока при цукровому діабеті вважаються тромбоцити (Тц). Мета: дослідити роль порушень функціонального стану тромбоцитів у розвитку діабетичної ретинопатії при цукровому діабеті 2-го типу. Матеріали та методи. Спостереження проводилося за 100 пацієнтами (100 очей) із ЦД2 і різними стадіями ДР. Дослідження пацієнтів було проведено на момент звернення пацієнта по спеціалізовану медичну допомогу, до початку лікування. У дослідженні використали наступні агоністи (індуктори агрегації): аденозиндифосфат (АДФ); адреналін; колаген; ангіотензин-2; фактор активації Тц (ФАТ). Статистичний аналіз проводили за допомогою пакета програм MedStat, MedCalc v. 17 і пакета побудови й аналізу нейромережевих моделей Statistica Neural Networks v.4.0 B. Результати. У результаті досліджень встановлено, що при ДР у пацієнтів неоднозначно змінюється відповідь Тц на агоністи — адреналін, колаген, ангіотензин-2, ФАТ і АДФ, яка обумовлена наявністю різних кластерів функціональної активності рецепторів. У пацієнтів з непроліферативною ДР виявлено протромбогенний (гіперадренореактивний) фенотип тромбоцитів, який може створювати умови для прогресування захворювання при дії колагену, ангіотензину-2 і ФАТ. У пацієнтів з проліферативною ДР прогресування геморагій, розвиток запалення й неоваскуляризація відбуваються за участю протромбогенного (гіперангіотензинового) фенотипу Тц, який характеризується високою реакцією на АДФ і ФАТ. На основі отриманих даних розроблена й впроваджена в практику нейромережева модель прогнозування розвитку стадій ДР. Висновки. 1. У пацієнтів із ДР уперше встановлено підвищення функціональної активності GPVI-рецепторів до колагену, α2-адрено- і АТ1-рецепторів, пуринових (Р2Y1 P2Y12) і ФАТ-рецепторів тромбоцитів, що проявлялося різними фенотипами і кластерами рецепторів. Даний феномен відображав індивідуальну реактивність пацієнтів стосовно впливу патогенетичних факторів ЦД (експозиції колагену стінки судин, активації симпатоадреналової і ренін-ангіотензинової систем, автокринної стимуляції тромбоцитів і розвитку запалення) на тромбогенез. 2. Встановлено збільшення вмісту прозапального цитокіну ІЛ-1β у сироватці крові пацієнтів із ЦД2 без змін на очному дні у два рази (р < 0,001) порівняно з контролем. Висока кореляція значень адреналін- (r = 0,805; р < 0,001) і ФАТ-індукованої (r = 0,604; р < 0,01) агрегації тромбоцитів з рівнем ІЛ-1β свідчила про зв’язок між реактивністю Тц і системною запальною реакцією. 3. На підставі отриманих результатів дослідження вперше була розроблена й упроваджена в практику нейромережева модель прогнозування стадій ДР. Лінійна модель прогнозування стадій захворювання заснована на аналізі двох факторних ознак — агрегації тромбоцитів, що індукована колагеном і АДФ; точність прогнозу становила 81,8 % (95% ДІ 73,5–88,8 %).

To date, all the factors that determine the speed and nature of the development and progression of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) have not been fully established. The development of informative methods to diagnose and predict the course of intraretinal microcirculation disorders in DR is relevant. Platelets are considered an important factor in the development of retinal hemorrhages in diabetes. Purpose: to investigate the role of platelet function disorders in the development of diabetic retinopathy in type 2 diabetes. Materials and methods. Observation involved 100 patients (100 eyes) with T2DM and various stages of DR. Examination was carried out at the time of the patient’s application for specialized medical care before the start of treatment. The following agonists (aggregation inducers) were used in the study: adenosine diphosphate (ADP); adrenalin; collagen; angiotensin II; platelet-activating factor (PAT). Statistical analysis was performed using the MedStat, MedCalc v. 17 and the package for building and analyzing neural network models Statistica Neural Networks v. 4.0B. Results. The research has found that in patients with DR, platelet response to agonists such as adrenaline, collagen, angiotensin II, PAT, and ADP changes ambiguously, which is due to the presence of different clusters of receptor functional activity. In patients with non-proliferative DR, a prothrombogenic (hyperadrenoreactive) phenotype of platelets was found, which can create conditions for the progression of the disease under the influence of collagen, angiotensin II and PAT. In patients with proliferative DR, the progression of hemorrhages, the development of inflammation, and neovascularization occur with the participation of prothrombogenic (hyperangiotensin) phenotype of platelets, which is characterized by a high response to ADP and PAT. Based on the obtained data, a neural network model for predicting the development of DR stages was developed and put into practice. Conclusions. 1. An increase in the functional activity of glycoprotein VI receptors to collagen, α2 adrenergic and angiotensin I receptors, purinergic (P2Y1 P2Y12) and PAT receptors of platelets was detected for the first time in patients with DR, it manifested by different phenotypes and receptor clusters. This phenomenon reflected the individual reactivity of patients to the influence of pathogenetic factors of DM (exposure of vascular wall collagen, activation of the sympathoadrenal and renin-angiotensin systems, autocrine stimulation of platelets and the development of inflammation) on thrombogenesis. 2. A two-fold increase was found in the serum content of the pro-inflammatory cytokine interleukin-1β without changes in the fundus (p < 0.001) in patients with T2DM compared to controls. A high correlation of adrenaline- (r = 0.805; p < 0.001) and PAT-induced (r = 0.604; p < 0.01) platelet aggregation with the level of interleukin-1β testified to the relationship between platelet reactivity and systemic inflammatory response. 3. Based on the research results, a neural network model for predicting the stages of DR was developed and put into practice for the first time. The linear model for predicting disease stages is based on the analysis of two factors: platelet aggregation induced by collagen, and ADP; the prediction accuracy was 81.8 % (95% CI 73.5–88.8 %).

 Our results on the action of mitomycin C in the treatment of urethral stricture indicate an additional effect on the regulatory system of the cell, in particular, disruption of the arginase / NO-synthase system of blood lymphocytes, leading to an imbalance of lymphocyte regulatory systems and NO regulatory function. Decreased H 2O2-induced iNOS activity by mitomycin C suggests that these antibiotics may prevent NO overproduction in blood lymphocytes. Nitric oxide, which is produced in excess in pathological conditions of the body, has a pronounced cytotoxic effect due to the formation of peroxynitrite – a product of the interaction of NO and superoxidanion-radical, capable of destroying almost all components of the cell. It is likely that one of the mechanisms of action of mitomycin C is a decrease in hyperproduction of NO. 

 Development and progression of chronic kidney disease (CKD) in patients with renal cell carcinoma (RCC) after radical nephrectomy remains an  extremely pressing contemporary issue. Postoperative changes of the ultrasound resistance index (RI) in the contralateral kidney not affected by the tumor after surgical treatment of RCC, as well as correlations between changes in IR and in glomerular filtration rate (GFR) remain far from being comprehensively investigated. The RI changes in the parenchyma of the intact (unaffected by the tumor) kidney before and after surgical treatment for RCC, and establishing correlations between RI changes and creatinine-dependent GFR remain unexplored issues. 

 In order to determine ADC, a region of interest (ROI) was established on the ADC map above the required area (prostatic neoplasm, lymph node or normal tissue) with the lowest ADC value identified as the zone with the largest hypo-intensity of MR signal. Taking into consideration that DWIs are morpho-functional images with limited morphological information, in order to improve the accuracy of anatomical comparisons of suspicious areas, we additionally performed mutual overlap of axial T2-WIs and DWIs using RadiAnt DICOM Viewer 2020.2.3 software package, obtaining a color map, where color intensities corresponded to the degrees of diffusion restriction, allowing for accurate spotting of the abnormal lesions detected on DWIs. To obtain the precise ROI position above the area of the lymph node analyzed on ADC maps, we copied the ROI from the respective slice of axial T1-WIs or T2-WIs, which have served as a precise anatomical landmark. In addition to that, to ensure more precise identification of lymph nodes, we proposed a DWIbased method of pelvic lymph node mapping using a maximum intensity projection algorithm, which facilitated spatial identification of lymph nodes and preoperative preparation (Fig. 1). No significant differences were observed when comparing mean sizes of N+ and N– pelvic lymph nodes (p > 0.05). At the same time, when comparing  mean ADC values for N+ and N– pelvic lymph nodes, we did observe a  tatistically significant difference: in metastatic lymph node involvement, this value was 0.74 ± 0.09 × 10-3 mm2/s, while in lymph nodes without  metastatic involvement this value was 1.05 ± 0.23 • 10-3 mm2/s (p < 0.001). Such findings reflect diffusion restriction of hydrogen molecules in N+ lymph nodes due to the increased cellular density in their tissues, which is the case in the development of malignant tumors (Fig. 2). The ROC-analysis using the ADC of DWI MRI for differentiation of N+ and N– pelvic lymph nodes in PCa has shown that in a threshold cut-off value of 0.87 •
10-3 mm2/s, the sensitivity and specificity were 87% and 75%, respectively, with a high accuracy of the method, area under the curve = 0.933; 95% confidence interval (CI) = 0.852–1.0; p < 0.001 (Fig. 3)