Аспергиллезно-стафилококковая пневмония у больного хроническим лимфолейкозом

В последние годы отмечается увеличение числа заболеваний органов дыхания, вызванных повсеместно распространенными в природе плесневыми грибами — аспергиллами. Большинство исследователей указывают на вторичный характер микозов у больных с нарушениями иммунологического статуса и при дисбактериозах

Патоморфологические и молекулярно-генетические особенности диффузного типа рака желудка

 Gastric cancer (GC) is the 5th most common type of cancer in the world and the third leading cause of death from cancer. GC is a multi-factorial and morphologically heterogeneous disease. Currently, several morphological classifications of GC are used, however, for diagnosis, it is necessary to take into  account not only the morphological type of the tumor, but also its molecular subtype. According to the literature, the intestinal type of GC is most often associated with effects of environmental factors and is usually found in older  age groups in men, while diffuse gastric cancer (DGC) is a genetically determined disease which is more common in younger patients, with the same frequency among men and women.This review covers in detail GC, its classification by P.A. Lauren (1965), and its molecular subtypes characterized during the Cancer Genome Atlas project and examines the impact of certain risk factors on the pathogenesis of the disease, such as: H. pylori infection or Epstein – Barr virus. A separate section in this analytical work is dedicated to expression of the PD-L1 marker by tumor cells and the use of this parameter for prognosis and therapy of this disease. An essential part of the work is discussion of the features of intestinal and diffuse types of gastric cancer, which reflect not only the differences in classifications used in modern diagnosis, but also the relationship between the pathological pattern and the molecular subtype of gastric cancer.  Рак желудка (РЖ) занимает пятое место в мире по распространенности среди всех злокачественных новообразований и является третьей по значимости причиной смертности от онкологических заболеваний. РЖ является мультифакториальным, морфологически  неоднородным заболеванием. В настоящее время используется несколько морфологических классификаций  РЖ, однако для постановки диагноза требуется учитывать не только морфологический тип опухоли, но и ее  молекулярный подтип. По данным литературы, РЖ  интестинального типа чаще всего ассоциирован с  действием факторов окружающей среды и, как правило, встречается в старших возрастных группах у мужчин.  Диффузный тип рака желудка (ДТРЖ) является в большей степени генетически детерминированным заболеванием и чаще встречается у более молодых пациентов, при этом с одинаковой частотой среди мужчин и женщин.В данном обзоре подробно освещается тема РЖ, его  классификация по P.A. Lauren (1965), его молекулярным  подтипы, охарактеризованные в Атласе ракового генома  (The Cancer Genome Atlas), а также рассматривается влияние  определенных факторов риска на патогенез  заболевания, таких как инфицирование H. pylori или вирусом Эпштейна – Барр. Отдельную роль в данной  аналитической работе занимает вопрос экспрессии опухолевыми клетками маркера PD-L1 и использование  данного параметра для прогнозирования и терапии этого  заболевания. Немаловажной частью работы является  обсуждение особенностей интестинального и диффузного  типов рака желудка, которые отражают не только различия  используемых в современной диагностике классификаций,  но и взаимосвязь патоморфологической картины с  молекулярным подтипом рака желудка.

Modern opportunities of pathology in diagnostics of early gastric cancer

For study of morphological, immunohistochemical and molecular-genetic features of early gastric cancer (EGC, Including the infection of Helicobacter pylori (Hp), fragments of gastric cancer with adjacent tissues of the mucous, deleted using endoscopic surgery in 50 patients aged 34-79 years (mean age 63.8 years). Performing complex morphological and IHC studies allows to diagnose EGC, namely the ability to evaluate the histological type and depth of invasion EGC, the presence or absence of tumor emboli in the blood and lymph vessels, which is crucial for determining treatment strategy and prognosis. Rated immunophenotype HgO and EGC a number of antibodies (cytokeratins 7,8/18, mucin 1,2 and 5AC, p53), the most indicative of which, in our opinion, were the antibodies to p53 and mucin5AC. Using PCR, we studed the frequency of mutations of BRAF and KRAS in the EGC, and HER2 amplification. A comparative analysis of the detectability of Hp was carried out using various methods of investigation.С целью изучения морфологических, иммуногистохимических и молекулярно-генетических особенностей раннего рака желудка (РРЖ), в том числе инфицированности Helicobacter pylori (Нр) были исследованы фрагменты опухолевой ткани желудка с прилежащими участками слизистой оболочки, удаленные с помощью органосохраняющих эндоскопических операций у 50 пациентов в возрасте от 34 до 79 лет (средний возраст 63,8 лет). Выполнение комплексного морфологического и ИГХ-исследования позволяет своевременно диагностировать РРЖ, оценить гистологический тип и глубину инвазии РРЖ, наличие или отсутствие раковых эмболов в кровеносных и лимфатических сосудах, что имеет решающее значение для определения лечебной тактики и прогноза. Изучен иммунофенотип РРЖ с рядом антител (АТ) (цитокератины 7,8/18, муцины 1,2 и 5АС, р53), наиболее показательными из которых, на наш взгляд, явились АТ к р53 и муцину SAC. При помощи ПЦР в режиме реального времени уточнена частота встречаемости мутаций BRAF и KRAS в РРЖ, а также HER2 амплификация. Проведен сравнительный анализ выявляемости Нр при помощи различных методов исследования

The Immune Profile of the Endometrium in the "Uterine Factor" of Infertility

Background: This study aimed to investigate the endometrial characteristics (pathomorphological and immunological) of women with infertility. Methods and Results: Data from an immunohistochemical study of endometrial biopsies (TNF-α, IL-10, GM-CSF, CXCL16, BCA1, TGF-β1) collected during the “implantation window” and microbiota studied by real-time polymerase chain reaction in 171 patients (21 women with unexplained infertility, 36 - chronic endometritis, 74 - tubal-peritoneal infertility, 22 - external genital endometriosis, 8 - "thin" endometrium, and 10 healthy fertile women from the comparison group) were analyzed to identify molecular signatures. Chronic endometritis was verified morphologically and immunohistochemically. Each group revealed different immune endometrial phenotypes. The basis of the "normal" phenotype was a controlled immune inflammation and a Lactobacillus-dominant microbiota (LDM) type. In contrast to the comparison group, in the group with the phenotype of chronic inflammation, an excessive immune response (overexpression of TNF-α, GM-CSF, CXCL16, BCA1, and a decrease in IL-10 and TGF-β1 in glandular epithelium and stroma) was determined on the background of non-Lactobacillus-dominated microbiota (NLDM) type (63.3%) (P<0.001). The peculiar feature of a dysplastic phenotype was a "poor" immune response, with maximal TGF-β1 overexpression (P<0.001) and a NLDM type (47.1%). We determined an excessive immune response in the proliferative endometrial phenotype (GM-CSF overexpression by 1.2 times in the glandular epithelium and stroma [P<0.001 in both cases] and a decrease in IL-10 by 1.6 times in the glandular epithelium and 1.2 times in the stroma [P<0.001 in both cases]). Uterine microbiome disorders were detected less frequently than in patients with the inflammation phenotype (31.6%) (P=0.01). In the phenotype with impaired immune status, there was a decrease in GM-CSF, BCA1, CXCL16, TNF-α, and IL-10 markers in both endometrial compartments (P<0.001) with a LDM type (81.2%). Conclusion. The molecular signatures of the endometrium are due to the heterogeneity of immune factors and microbiota. Aberrant expression of immune factors may contribute to the formation of a microenvironment unfavorable for blastocyst implantation

Технологическая адекватность продукции свеклосахарного производства, используемой в пищевой промышленности

Beet sugar production in Russia annually gives about 6 million tons of white sugar and 1.5 million tons of beet molasses, which must have technological adequacy, when used as raw materials. The purpose of the work was to substantiate the concept of technological adequacy of beet sugar production, its indicator markers and their threshold values, to assess the actual technological adequacy of white sugar and molasses, to verify the hypothesis about the relationship between individual indicators of white sugar and empirical knowledge about an increase in the content of micronutrients with a decrease in the category. The objects of the study were terminology related to the characteristics of food products and raw materials in terms of consumer expectations and indicators of their assessment. Technological adequacy was evaluated for 230 samples of white sugar and 134 samples of beet molasses. Indicator markers were determined according to standardized and known methods. Technological adequacy of white sugar and beet molasses is the compliance of their specific functional properties with the requirements of the production of a particular food product, in which they are raw ingredients. A measure of compliance is indicator markers in the form of physicochemical parameters of the composition. Indicators of white sugar for three food technologies and indicators of beet molasses for two technologies and storage were substantiated; their technological adequacy was assessed. Empirical knowledge about an increase in the content of micronutrients with a decrease in the category and the hypothesis about the relationship between individual indicators of white sugar were confirmed. It is shown that all white sugar of extra and TC1 categories has technological adequacy for the use in food production, while only 62% of TC2 sugar and some batches of beet molasses have the necessary technological suitability. The results obtained will be a tool for regulating the production of competitive products and developing a control scheme for the technological flow of sugar production.Свеклосахарное производство России ежегодно вырабатывает около 6 млн т белого сахара и 1,5 млн т свекловичной мелассы, которые при потреблении в качестве сырья должны обладать технологической адекватностью. Цель работы — обоснование понятия технологической адекватности продукции свеклосахарного производства, ее индикаторных показателей и их пороговых значений, оценка фактической технологической адекватности белого сахара и мелассы; проверка гипотезы о взаимосвязи отдельных показателей белого сахара и эмпирических знаний о повышении содержания микронутриентов при понижении категории. Объектами исследования являлась терминология, относящаяся к характеристикам пищевых продуктов и сырья с точки зрения ожидания потребителей и показатели их оценки. Технологическую адекватность оценивали для 230 образцов белого сахара и 134 образцов свекловичной мелассы, индикаторные показатели определяли по стандартизованным и известным методикам. Технологическая адекватность белого сахара и свекловичной мелассы — соответствие определенных их функциональных свойств требованиям производства конкретного пищевого продукта, в котором они являются сырьевым ингредиентом. Мерой соответствия служат индикаторные показатели в виде физико-химических параметров состава. Обоснованы индикаторные показатели белого сахара для 3 технологий пищевых продуктов; свекловичной мелассы — для 2 технологий и хранения; выполнена оценка их технологической адекватности. Подтверждены эмпирические знания о повышении содержания микронутриентов при понижении категории, а также гипотеза о взаимосвязи отдельных показателей белого сахара. Показано, что весь белый сахар категорий экстра и ТС1 обладает технологической адекватностью для использования в производстве пищевой продукции, в то время как только 62% сахара категории ТС2 и некоторые партии свекловичной мелассы обладают необходимой технологической пригодностью. Полученные результаты будут являться инструментом регулирования выпуска конкурентоспособной продукции и развития схемы контроля технологического потока производства сахара

Ischemic Changes in the Mucous Membrane of the Transverse Colon as a Complication of Acute Pancreatitis

Aim: to present a clinical case of a patient with a complicated course of acute pancreatitis.Key points. A 31-year-old patient was admitted to the surgical department with a clinical picture of acute alcoholic pancreatitis. Signs of anemia were regarded as a consequence of gastrointestinal bleeding. Computed tomography with contrast enhancement, along with an increase in the size of the pancreas, the presence of foci of pancreatic necrosis with multiple fluid accumulations in the parapancreatic space, revealed smoothed gaustration and thickening of the walls of the predominantly transverse colon. During colonoscopy, ischemic changes of the colon mucosa were detected in a timely manner. Negative results of analysis for toxins A and B of Clostridioides difficile and pathogenic intestinal flora were obtained. By the means of intensive care, it was possible to achieve complete stabilization of the patient's condition, normalization of laboratory blood parameters and relief of ischemic processes in the colon wall.Conclusion. Ischemic changes of the colon can serve as a complication of acute pancreatitis. A thorough analysis of the results of computed tomography at the first signs of colon lesion and colonoscopy contributed to the rapid detection of complications and prevention of irreversible colon ischemia

Diagnosis of Columnar Metaplasia of the Esophageal Mucosa in Patients with Complicated Gastroesophageal Reflux Disease

Aim: to improve methods of diagnostics of esophageal mucosal forms of metaplasia and dysplasia in patients with complicated forms of gastroesophageal reflux disease (GERD) using multidisciplinary approach.Material and methods. Overall, 131 patients aged 18 to 84 years (mean age — 55.8 ± 16.7 years) with confirmed diagnosis of GERD complicated by development of metaplasia of mucosa of distal esophagus were included in retroand prospective study. At the prehospital stage the patients' complaints were estimated, anamnesis was taken. At the first stage of the diagnostic program all patients underwent detailed esophagogastroduodenoscopy in high resolution with white light. The region of esophageal mucosa with signs of metaplasia and determination of its prevalence was examined and evaluated with special attention. Ultrashort segment was revealed in 26 patients, short segment — in 47 patients, long segment of mucosal metaplasia was revealed in 58 patients. Then to reveal the signs of dysplasia we used specifying endoscopic methods: the structure of pitted and microvascular pattern was estimated in narrow spectral mode using BING classification system. If an irregular type of metaplasized epithelium structure was detected in the process of BING assessment, the areas suspicious for dysplasia were marked, followed by aim forceps biopsy from them. The next stage was staining of the metaplasized segment with 1.5 % ethanic acid solution — acetowhitening. PREDICT classification system was used to evaluate the stained mucosal sections with metaplasia. Targeted forceps biopsy was performed from the altered areas that most quickly lost their coloring. The final stage of the diagnostic program in all patients was a forceps biopsy of the mucosa of the metaplasic segment according to the Seattle protocol, which requires increasing the number of fragments as the metaplasic segment lengthens in a “blind” biopsy. The biopsy material was stained with hematoxylin and eosin, and periodic acid Schiff reaction was performed in combination with alcyanine blue according to the standard technique.Results. Endoscopic examination in white light and evaluation of metaplasia extent revealed ultrashort segment (&lt;1 cm) in 26/131 (19.9 %) patients; short segment (1–3 cm) — in 47/131 (35.9 %); long segment (&gt; 3 cm) — in 58/131 (44.3 %) patients. Among the diagnostic techniques used, the BING and PREDICT classifications had the highest accuracy, sensitivity, and specificity (accuracy — 88.9 and 95.3 %, sensitivity — 90.5 and 91.3 %, and specificity — 86.7 and 100 %, respectively), which significantly exceeded the Seattle protocol also used in this work. The results showed a low level of specificity (31.2 %), accuracy (54.5 %), and sensitivity (76.8 %) of the Seattle protocol. The use of BING and PREDICT classifications provided marking of compromised zones, allowing targeted histological sampling.Conclusions. The original study demonstrated the greatest sensitivity, specificity, and accuracy of PREDICT and BING methods in the diagnosis of metaplasia with signs of dysplasia in patients with complicated GERD. It is also important that the use of BING and PREDICT classification systems allows to reduce the number of biopsy samples in comparison with their unreasonably large number according to the Seattle protocol, thereby reducing mucosal and submucosal trauma of the esophagus and the risk of complications

YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.

Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder. Cases with YWHAE variants were collected through international data sharing networks. To address the specific impact of YWHAE loss of function, we phenotyped a mouse knockout of Ywhae. We report a series of 10 individuals with heterozygous loss-of-function YWHAE variants (3 single-nucleotide variants and 7 deletions &lt;1 Mb encompassing YWHAE but not PAFAH1B1), including 8 new cases and 2 follow-ups, added with 5 cases (copy number variants) from literature review. Although, until now, only 1 intragenic deletion has been described in YWHAE, we report 4 new variants specifically in YWHAE (3 splice variants and 1 intragenic deletion). The most frequent manifestations are developmental delay, delayed speech, seizures, and brain malformations, including corpus callosum hypoplasia, delayed myelination, and ventricular dilatation. Individuals with variants affecting YWHAE alone have milder features than those with larger deletions. Neuroanatomical studies in Ywhae &lt;sup&gt;-/-&lt;/sup&gt; mice revealed brain structural defects, including thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus paralleling those seen in humans. This study further demonstrates that YWHAE loss-of-function variants cause a neurodevelopmental disease with brain abnormalities

Comparative morphological characteristics of the uteroplacental area in abnormal placentation

The aim. To carry out a comparative morphological characteristic of the uteroplacental area with abnormal placentation – pl. accreta, pl. increta, pl. percreta. Materials and methods. The study included 47 patients with atypical placentation; the comparison group included 10 healthy pregnant women with uterine scar after a previous caesarean section. A histological study of uteroplacental area samples was performed with hematoxylin and eosin, methylene blue staining. An immunohistochemical study with primary antibodies to cytokeratin 7 (CK7), Hif2a, vascular endothelial growth factor, α-SMA was carried out. The differences between the compared values were considered to be statistically significant at p &lt; 0.05. The results of the study. Pl. accreta was determined in 12 (25.5 %), pl. increta – in 30 (63.9 %), pl. percreta – in 5 (10.6 %) patients. In all patients of the main group, the decidua was completely or partially absent in the area of abnormal placentation or was replaced by an uneven layer of fetal fibrinoid. Cases when placental villi unevenly penetrated into the thickness of myometrium in the form of “tongues” or “coves” bordered by fetal fibrinoid and often located intermuscularly were defined as pl. increta (n = 26). Cases with the placental villi ingrowth to the serous membrane were considered as pl.  percreta (n  =  5). In cases with deep variants of  ingrowth (pl. increta and pl. percreta) (n = 31), the villi were visualized in the lumen of the vessels and the thinning of the lower uterine segment with the presence of stretched muscle bundles was revealed. Aseptic necrosis of  the myometrium was  found: in 2 (16.7 %) of 12 women with pl. accreta, in 26 (86.7 %) of 30 women with pl. increta and in 5 (100 %) women with pl. percreta. There were no areas of necrosis in the myometrium of the women of comparison group. Conclusion. The appearance and increase of myometrial necrosis zones in response to an increase in the depth of placental villus ingrowth were detected. Myometrial necrosis zones could be the cause of activation of angiogenic factors and an important stimulus for the development of abnormal vascularization in placenta accreta spectrum