Pub Date : 2024-02-11DOI: 10.18786/2072-0505-2023-51-050
S. A. Gasparyan, A. G. Topuzov, I. A. Orfanova, S. M. Akhmedova
The review summarizes current understanding of neutrophil extracellular traps (NETs) and their role in the development of inflammation and thrombus formation during physiological and complicated pregnancy. The main initiation factors and molecular and cellular reactions leading to the generation of NETs are described. During gestation, various pregnancy-associated triggers (cytokines, hormones, colony-stimulating factors, etc.) contribute to increased activity of innate immune factors associated with the processes of neutrophil migration into gestational tissues, adhesion, degranulation, phagocytosis and release of extracellular neutrophil traps. It has been established that the uncontrolled aberrant generation of NETs, as well as their products, including reactive oxygen species, can exert a cytotoxic effect on maternal cells and tissues, adverse fetal effects and contribute to placental damage, resulting in such pregnancy complications as placental disorders, immunothrombosis and preeclampsia. The emergence of new data on the morphological and functional characteristics of the cellular component of innate immunity necessitates their advanced research with consideration of the functional potential and conditions for NETs formation, clarification and determination of their pathophysiological significance in normal and complicated pregnancy. It seems promising to study the possibility of assessment of the DNA traps levels for early diagnosis and prognosis of gestational complications, as well as for the development of new treatment strategies including targeted therapy.
这篇综述总结了目前对中性粒细胞胞外捕获物（NETs）及其在生理性妊娠和复杂妊娠期间炎症发展和血栓形成过程中作用的认识。文中描述了导致 NETs 生成的主要启动因子以及分子和细胞反应。在妊娠期间，各种与妊娠相关的诱发因素（细胞因子、激素、集落刺激因子等）会增加与中性粒细胞迁移到妊娠组织、粘附、脱颗粒、吞噬和释放细胞外中性粒细胞捕获物等过程相关的先天性免疫因子的活性。已经证实，不受控制的嗜中性粒细胞的异常生成及其产物，包括活性氧，可对母体细胞和组织产生细胞毒性作用，对胎儿产生不利影响，并造成胎盘损伤，导致胎盘功能紊乱、免疫血栓和子痫前期等妊娠并发症。有关先天性免疫细胞成分的形态和功能特征的新数据的出现，要求对其进行深入研究，考虑 NETs 的功能潜力和形成条件，阐明并确定其在正常妊娠和复杂妊娠中的病理生理意义。研究对 DNA 陷阱水平进行评估的可能性似乎很有希望，以用于妊娠并发症的早期诊断和预后，以及开发新的治疗策略，包括靶向治疗。
{"title":"Neutrophil extracellular traps: molecular and cellular mechanisms of formation, role in the development of placental disorders and preeclampsia","authors":"S. A. Gasparyan, A. G. Topuzov, I. A. Orfanova, S. M. Akhmedova","doi":"10.18786/2072-0505-2023-51-050","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-050","url":null,"abstract":"The review summarizes current understanding of neutrophil extracellular traps (NETs) and their role in the development of inflammation and thrombus formation during physiological and complicated pregnancy. The main initiation factors and molecular and cellular reactions leading to the generation of NETs are described. During gestation, various pregnancy-associated triggers (cytokines, hormones, colony-stimulating factors, etc.) contribute to increased activity of innate immune factors associated with the processes of neutrophil migration into gestational tissues, adhesion, degranulation, phagocytosis and release of extracellular neutrophil traps. It has been established that the uncontrolled aberrant generation of NETs, as well as their products, including reactive oxygen species, can exert a cytotoxic effect on maternal cells and tissues, adverse fetal effects and contribute to placental damage, resulting in such pregnancy complications as placental disorders, immunothrombosis and preeclampsia. The emergence of new data on the morphological and functional characteristics of the cellular component of innate immunity necessitates their advanced research with consideration of the functional potential and conditions for NETs formation, clarification and determination of their pathophysiological significance in normal and complicated pregnancy. It seems promising to study the possibility of assessment of the DNA traps levels for early diagnosis and prognosis of gestational complications, as well as for the development of new treatment strategies including targeted therapy.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"104 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139785384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-11DOI: 10.18786/2072-0505-2023-51-044
Andreeva OV, Semenov NN, Shchekochikhin DYu, Novikova AI, Potemkina NA, Ozova MA, Kuli-Zade ZA, Levina VD, Shmeleva AA, Poltavskaya MG. Prevalence of endothelial dysfunction and increased vascular stiffness in patients with solid malignancies. Almanac of Clinical Medicine. 2022;50(2):103–110. doi: 10.18786/2072-0505-2022-50-022. Published online 13 July 2022 Table 2, instead of “Phase shift, m/s” should read “Phase shift, ms” This error does not affect the conclusions of the article. Both the HTML and PDF versions have been updated. Almanac of Clinical Medicine journal apologizes for the error.
{"title":"Correction to “Prevalence of endothelial dysfunction and increased vascular stiffness in patients with solid malignancies”","authors":"","doi":"10.18786/2072-0505-2023-51-044","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-044","url":null,"abstract":"Andreeva OV, Semenov NN, Shchekochikhin DYu, Novikova AI, Potemkina NA, Ozova MA, Kuli-Zade ZA, Levina VD, Shmeleva AA, Poltavskaya MG. Prevalence of endothelial dysfunction and increased vascular stiffness in patients with solid malignancies. Almanac of Clinical Medicine. 2022;50(2):103–110. doi: 10.18786/2072-0505-2022-50-022. Published online 13 July 2022 \u0000Table 2, instead of \u0000“Phase shift, m/s” \u0000should read \u0000“Phase shift, ms” \u0000This error does not affect the conclusions of the article. Both the HTML and PDF versions have been updated. Almanac of Clinical Medicine journal apologizes for the error.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"112 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139785256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-11DOI: 10.18786/2072-0505-2023-51-049
O.V. Shcherbakova
From the beginning of 2000s, there has been a significant increase in the incidence of inflammatory bowel diseases (IBD) and primary immunodeficiency disorders (PIDs) in adults and children in many countries around the world. The aim of the review is to summarize the state-of-the-art on diverse clinical types of PIDs with gastrointestinal manifestations and their differential diagnostic algorithms. Atypical PIDs with “blunted” clinical manifestations are challenging for the timely diagnosis. Some types of PIDs with gastrointestinal involvement are also difficult to differentiate with classical IBDs. Molecular genetic studies have allowed for selection of a specific group of monogenic IBD-like diseases, represented mainly by PIDs. The authors discuss current classification of PIDs and their main clinical types imitating IBD, with important clinical and laboratory aspects. High level of information and awareness of practicing specialists working with IBD patients would be helpful in the selection of a patient cohort with possible PIDs and in the performance of extended laboratory assessment or referring for genetic tests. Timely diagnosis of PIDs would ensure quick administration of target therapy or hematopoietic stem cell transplantation, which in most cases would allow for the achievement of the disease remission, improvement of quality and duration of life.
{"title":"Primary immunodeficiency disorders imitating inflammatory bowel diseases: clinical aspects and problems of the differential diagnosis","authors":"O.V. Shcherbakova","doi":"10.18786/2072-0505-2023-51-049","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-049","url":null,"abstract":"From the beginning of 2000s, there has been a significant increase in the incidence of inflammatory bowel diseases (IBD) and primary immunodeficiency disorders (PIDs) in adults and children in many countries around the world. The aim of the review is to summarize the state-of-the-art on diverse clinical types of PIDs with gastrointestinal manifestations and their differential diagnostic algorithms. \u0000Atypical PIDs with “blunted” clinical manifestations are challenging for the timely diagnosis. Some types of PIDs with gastrointestinal involvement are also difficult to differentiate with classical IBDs. Molecular genetic studies have allowed for selection of a specific group of monogenic IBD-like diseases, represented mainly by PIDs. The authors discuss current classification of PIDs and their main clinical types imitating IBD, with important clinical and laboratory aspects. High level of information and awareness of practicing specialists working with IBD patients would be helpful in the selection of a patient cohort with possible PIDs and in the performance of extended laboratory assessment or referring for genetic tests. Timely diagnosis of PIDs would ensure quick administration of target therapy or hematopoietic stem cell transplantation, which in most cases would allow for the achievement of the disease remission, improvement of quality and duration of life.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"36 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139845950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-11DOI: 10.18786/2072-0505-2023-51-049
O.V. Shcherbakova
From the beginning of 2000s, there has been a significant increase in the incidence of inflammatory bowel diseases (IBD) and primary immunodeficiency disorders (PIDs) in adults and children in many countries around the world. The aim of the review is to summarize the state-of-the-art on diverse clinical types of PIDs with gastrointestinal manifestations and their differential diagnostic algorithms. Atypical PIDs with “blunted” clinical manifestations are challenging for the timely diagnosis. Some types of PIDs with gastrointestinal involvement are also difficult to differentiate with classical IBDs. Molecular genetic studies have allowed for selection of a specific group of monogenic IBD-like diseases, represented mainly by PIDs. The authors discuss current classification of PIDs and their main clinical types imitating IBD, with important clinical and laboratory aspects. High level of information and awareness of practicing specialists working with IBD patients would be helpful in the selection of a patient cohort with possible PIDs and in the performance of extended laboratory assessment or referring for genetic tests. Timely diagnosis of PIDs would ensure quick administration of target therapy or hematopoietic stem cell transplantation, which in most cases would allow for the achievement of the disease remission, improvement of quality and duration of life.
{"title":"Primary immunodeficiency disorders imitating inflammatory bowel diseases: clinical aspects and problems of the differential diagnosis","authors":"O.V. Shcherbakova","doi":"10.18786/2072-0505-2023-51-049","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-049","url":null,"abstract":"From the beginning of 2000s, there has been a significant increase in the incidence of inflammatory bowel diseases (IBD) and primary immunodeficiency disorders (PIDs) in adults and children in many countries around the world. The aim of the review is to summarize the state-of-the-art on diverse clinical types of PIDs with gastrointestinal manifestations and their differential diagnostic algorithms. \u0000Atypical PIDs with “blunted” clinical manifestations are challenging for the timely diagnosis. Some types of PIDs with gastrointestinal involvement are also difficult to differentiate with classical IBDs. Molecular genetic studies have allowed for selection of a specific group of monogenic IBD-like diseases, represented mainly by PIDs. The authors discuss current classification of PIDs and their main clinical types imitating IBD, with important clinical and laboratory aspects. High level of information and awareness of practicing specialists working with IBD patients would be helpful in the selection of a patient cohort with possible PIDs and in the performance of extended laboratory assessment or referring for genetic tests. Timely diagnosis of PIDs would ensure quick administration of target therapy or hematopoietic stem cell transplantation, which in most cases would allow for the achievement of the disease remission, improvement of quality and duration of life.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"103 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139786106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-11DOI: 10.18786/2072-0505-2023-51-044
Andreeva OV, Semenov NN, Shchekochikhin DYu, Novikova AI, Potemkina NA, Ozova MA, Kuli-Zade ZA, Levina VD, Shmeleva AA, Poltavskaya MG. Prevalence of endothelial dysfunction and increased vascular stiffness in patients with solid malignancies. Almanac of Clinical Medicine. 2022;50(2):103–110. doi: 10.18786/2072-0505-2022-50-022. Published online 13 July 2022 Table 2, instead of “Phase shift, m/s” should read “Phase shift, ms” This error does not affect the conclusions of the article. Both the HTML and PDF versions have been updated. Almanac of Clinical Medicine journal apologizes for the error.
{"title":"Correction to “Prevalence of endothelial dysfunction and increased vascular stiffness in patients with solid malignancies”","authors":"","doi":"10.18786/2072-0505-2023-51-044","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-044","url":null,"abstract":"Andreeva OV, Semenov NN, Shchekochikhin DYu, Novikova AI, Potemkina NA, Ozova MA, Kuli-Zade ZA, Levina VD, Shmeleva AA, Poltavskaya MG. Prevalence of endothelial dysfunction and increased vascular stiffness in patients with solid malignancies. Almanac of Clinical Medicine. 2022;50(2):103–110. doi: 10.18786/2072-0505-2022-50-022. Published online 13 July 2022 \u0000Table 2, instead of \u0000“Phase shift, m/s” \u0000should read \u0000“Phase shift, ms” \u0000This error does not affect the conclusions of the article. Both the HTML and PDF versions have been updated. Almanac of Clinical Medicine journal apologizes for the error.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"44 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139845409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-25DOI: 10.18786/2072-0505-2023-51-047
Efim S. Korsunskiy, Elena A. Belousova, A. A. Budzinskaya
Background: Clinical signs of gastrointestinal disorders can manifest both from the first days of COVID-19 and after recovery, and may last up to 6 months or more. Most studies examined the gastrointestinal changes in acute coronavirus infection, whereas intestinal abnormalities in the early and late post-COVID period and their causes have not been sufficiently studied. Aim: To determine the frequency and types of clinical, endoscopic and morphological abnormalities in patients with post-COVID-19 intestinal lesions. Materials and methods: This was a prospective, observational, open-label, cohort, non-controlled study in 72 patients with intestinal symptoms after the coronavirus infection (female 48, mean age 54.6 (95% confidence interval 51.08–58.12) years), who were admitted to the Department of Gastroenterology of general hospital during the first and second waves of COVID-19 from June 2020 to September 2021. The assessment included routine anamnestic, clinical, laboratory, endoscopic, and morphological methods. When indicated, visualization methods (ultrasound, computed tomography, magnetic resonance imaging) were performed. The treatment was symptom-oriented and aimed at inflammation, anemia and protein and electrolyte abnormalities. Outcomes were assessed by the time of discharge from the hospital and thereafter by telephone interviewing of the patients for 8 weeks. Results: In all patients, the main symptom was diarrhea, which started right just after SARS-CoV-2 infection with negative PCR test or 2–4 weeks later. The average stool frequency was 6.8 (5.61–7.99) times daily. In 19/72 patients (26.4%), there were blood and mucus in stools. 2.8% of the patients developed massive intestinal bleeding. Fever was present in 40.3% of the patients, decreased hemoglobin levels in 44.4%, and hypoalbuminemia in 16.7%. Signs of systemic inflammation (increased erythrocyte sedimentation rate, C-reactive protein, fibrinogen, thrombocytosis, leukocytosis) were found with various frequencies in a half of the patients. Clostridioides difficile A and B toxins were identified in 38.9% of the cases and increased fecal calprotectin in 22.2%. Ileocolonoscopy was performed in 67 patients. The colonic mucosa in 21 (31.3%) patients either was not different from the normal, or showed minimal inflammatory changes such as absence of vascular pattern, hyperemia, mild friability even in patients with severe diarrhea, fever and laboratory abnormalities. Pseudomembranous colitis was diagnosed in 12 (17.9%) patients, and focal hemorrhagic colitis in 11 (16.4%) patients. In 2 (3%) cases, moderate to severe ulcerative colitis was newly diagnosed after the SARS-CoV-2 infection. Single or multiple erosions and ulcers of various sizes against the unchanged surrounding mucosa were found in 19 (28.4%) patients. In 2 (3%) cases with profuse intestinal bleeding, the endoscopy showed diffuse spontaneous bleedings from colonic mucosa, with no local source of bleeding found. Biops
{"title":"The post-COVID-19 intestinal damages: clinical, endoscopic and morphological features. The results of a single-center prospective observational cohort study","authors":"Efim S. Korsunskiy, Elena A. Belousova, A. A. Budzinskaya","doi":"10.18786/2072-0505-2023-51-047","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-047","url":null,"abstract":"Background: Clinical signs of gastrointestinal disorders can manifest both from the first days of COVID-19 and after recovery, and may last up to 6 months or more. Most studies examined the gastrointestinal changes in acute coronavirus infection, whereas intestinal abnormalities in the early and late post-COVID period and their causes have not been sufficiently studied. \u0000Aim: To determine the frequency and types of clinical, endoscopic and morphological abnormalities in patients with post-COVID-19 intestinal lesions. \u0000Materials and methods: This was a prospective, observational, open-label, cohort, non-controlled study in 72 patients with intestinal symptoms after the coronavirus infection (female 48, mean age 54.6 (95% confidence interval 51.08–58.12) years), who were admitted to the Department of Gastroenterology of general hospital during the first and second waves of COVID-19 from June 2020 to September 2021. The assessment included routine anamnestic, clinical, laboratory, endoscopic, and morphological methods. When indicated, visualization methods (ultrasound, computed tomography, magnetic resonance imaging) were performed. The treatment was symptom-oriented and aimed at inflammation, anemia and protein and electrolyte abnormalities. Outcomes were assessed by the time of discharge from the hospital and thereafter by telephone interviewing of the patients for 8 weeks. \u0000Results: In all patients, the main symptom was diarrhea, which started right just after SARS-CoV-2 infection with negative PCR test or 2–4 weeks later. The average stool frequency was 6.8 (5.61–7.99) times daily. In 19/72 patients (26.4%), there were blood and mucus in stools. 2.8% of the patients developed massive intestinal bleeding. Fever was present in 40.3% of the patients, decreased hemoglobin levels in 44.4%, and hypoalbuminemia in 16.7%. Signs of systemic inflammation (increased erythrocyte sedimentation rate, C-reactive protein, fibrinogen, thrombocytosis, leukocytosis) were found with various frequencies in a half of the patients. Clostridioides difficile A and B toxins were identified in 38.9% of the cases and increased fecal calprotectin in 22.2%. \u0000Ileocolonoscopy was performed in 67 patients. The colonic mucosa in 21 (31.3%) patients either was not different from the normal, or showed minimal inflammatory changes such as absence of vascular pattern, hyperemia, mild friability even in patients with severe diarrhea, fever and laboratory abnormalities. Pseudomembranous colitis was diagnosed in 12 (17.9%) patients, and focal hemorrhagic colitis in 11 (16.4%) patients. In 2 (3%) cases, moderate to severe ulcerative colitis was newly diagnosed after the SARS-CoV-2 infection. Single or multiple erosions and ulcers of various sizes against the unchanged surrounding mucosa were found in 19 (28.4%) patients. In 2 (3%) cases with profuse intestinal bleeding, the endoscopy showed diffuse spontaneous bleedings from colonic mucosa, with no local source of bleeding found. \u0000Biops","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"115 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139596732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.18786/2072-0505-2023-51-046
S. Goncharov, V. Bozhenko, M. V. Zakharenko, Y. Y. Kiseleva, Andrey A. Chaptykov, Tatiana M. Kulinich, T. Krashikhina, V. A. Solodkiy
Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC. Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon. Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables. Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space. Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic
{"title":"Analysis of molecular phenotypes in normal mucosa and colorectal cancer in embryonic anatomical parts of the colon","authors":"S. Goncharov, V. Bozhenko, M. V. Zakharenko, Y. Y. Kiseleva, Andrey A. Chaptykov, Tatiana M. Kulinich, T. Krashikhina, V. A. Solodkiy","doi":"10.18786/2072-0505-2023-51-046","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-046","url":null,"abstract":"Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC. \u0000Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon. \u0000Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables. \u0000Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space. \u0000Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139603577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.18786/2072-0505-2023-51-048
Polina V. Kulabukhova, Olga S. Kondrashina, Dmitriy M. Akinfiev, V. Bychenko
Background: Identification of residual chorionic tissue and ingrowing chorionic villi after uterine cavity curettage due to non-developing pregnancy, spontaneous abortions, and medical abortions has been a poorly studied problem. The most challenging is the differential diagnosis of this condition when the chorion grows into the scar from a caesarean section and is associated with arteriovenous malformations of the uterine wall. Nowadays, ultrasound has been recognized as the primary diagnostic method; however, the absence of specific echo-signs makes magnetic resonance imaging (MRI) and computed tomography (CT) the methods of choice and final diagnosis. Clinical case: This was a 39-year-old patient with a history of 3 caesarean sections and non-developing pregnancy and complete spontaneous miscarriage at 4 to 5 weeks of gestation in March 2021. Her final diagnosis was “growing of the chorionic villi of the first trimester of gestation into the myometrium to the entire depth of the uterine wall and up to the serous membrane without germination of the latter (placenta increta). At admission to the clinic in April 2021, she complained of pelvic pain, ongoing low intensity intermittent uterine bleeding, weakness, dizziness, and breast pain. The ultrasound revealed a mass in the uterine cavity. The MRI showed an incompetent post-cesarean uterine scar and residual chorionic tissue spreading to the uterine serosa, with peripheral arteriovenous structures of a neoangiogenous type. Multiaxial CT with angiography could not exclude an arteriovenous malformation within the uterine wall and residual chorionic tissue. During embolization, the angiograms showed the arteriovenous malformation in the projection of the uterus, with afferent vessels as bilateral uterine and cervicovaginal arteries and efferent vessels as bilateral parametric veins, internal iliac and ovarian veins. Based on the clinical and imaging pictures, embolization of the uterine arteries was performed as a first step and laparoscopic clipping of the uterine arteries and hysterectomy with fallopian tubes as a second step. Postoperatively the patient improved and beta-chorionic gonadotropin levels decreased. She was discharged home on the 5th day with no complaints. The clinical case demonstrates the important role of MRI and CT in the differential diagnosis and assessment of the zone and degree of chorionic villi ingrowth, aimed at determination of the possibility of organ-preserving treatment, or the need to perform a radical surgery should metroplasty be impossible. Conclusion: If an additional intrauterine mass is visualized by ultrasound examination after pregnancy termination, the method of choice and final diagnosis is MRI, which is performed to exclude the ingrown chorionic villi and to assess the degree of their invasion. MRI also allows for assessment of the viability of the post-cesarean scar and the presence of neoangiogenesis areas at the periphery of the ingrowth zone. CT is
{"title":"Ingrown chorionic villi of the first trimester as a result of a non-developing pregnancy in the post-cesarean scar, associated with the development of arteriovenous malformation: а cliniacal case","authors":"Polina V. Kulabukhova, Olga S. Kondrashina, Dmitriy M. Akinfiev, V. Bychenko","doi":"10.18786/2072-0505-2023-51-048","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-048","url":null,"abstract":"Background: Identification of residual chorionic tissue and ingrowing chorionic villi after uterine cavity curettage due to non-developing pregnancy, spontaneous abortions, and medical abortions has been a poorly studied problem. The most challenging is the differential diagnosis of this condition when the chorion grows into the scar from a caesarean section and is associated with arteriovenous malformations of the uterine wall. Nowadays, ultrasound has been recognized as the primary diagnostic method; however, the absence of specific echo-signs makes magnetic resonance imaging (MRI) and computed tomography (CT) the methods of choice and final diagnosis. \u0000Clinical case: This was a 39-year-old patient with a history of 3 caesarean sections and non-developing pregnancy and complete spontaneous miscarriage at 4 to 5 weeks of gestation in March 2021. Her final diagnosis was “growing of the chorionic villi of the first trimester of gestation into the myometrium to the entire depth of the uterine wall and up to the serous membrane without germination of the latter (placenta increta). At admission to the clinic in April 2021, she complained of pelvic pain, ongoing low intensity intermittent uterine bleeding, weakness, dizziness, and breast pain. The ultrasound revealed a mass in the uterine cavity. The MRI showed an incompetent post-cesarean uterine scar and residual chorionic tissue spreading to the uterine serosa, with peripheral arteriovenous structures of a neoangiogenous type. Multiaxial CT with angiography could not exclude an arteriovenous malformation within the uterine wall and residual chorionic tissue. During embolization, the angiograms showed the arteriovenous malformation in the projection of the uterus, with afferent vessels as bilateral uterine and cervicovaginal arteries and efferent vessels as bilateral parametric veins, internal iliac and ovarian veins. \u0000Based on the clinical and imaging pictures, embolization of the uterine arteries was performed as a first step and laparoscopic clipping of the uterine arteries and hysterectomy with fallopian tubes as a second step. Postoperatively the patient improved and beta-chorionic gonadotropin levels decreased. She was discharged home on the 5th day with no complaints. \u0000The clinical case demonstrates the important role of MRI and CT in the differential diagnosis and assessment of the zone and degree of chorionic villi ingrowth, aimed at determination of the possibility of organ-preserving treatment, or the need to perform a radical surgery should metroplasty be impossible. \u0000Conclusion: If an additional intrauterine mass is visualized by ultrasound examination after pregnancy termination, the method of choice and final diagnosis is MRI, which is performed to exclude the ingrown chorionic villi and to assess the degree of their invasion. MRI also allows for assessment of the viability of the post-cesarean scar and the presence of neoangiogenesis areas at the periphery of the ingrowth zone. CT is","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"74 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139604209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-18DOI: 10.18786/2072-0505-2023-51-045
V. Bozhenko, S. Goncharov, E. Kudinova, Tatiana M. Kulinich, Elena A. Kukoleva, Mikhail S. Filippov, Anna F. Bykova, Oksana B. Knyazeva, Ilya A. Puchkov, V. A. Solodkiy
Background: Ras oncogene mutations leading to hyperactivation of the MAPK/ERK signaling pathway occur in 25% of all human tumors, and for gastrointestinal tumors, the frequency of Ras mutations amounts to 60%. The introduction of a Ras-GTPase inhibitor into clinical practice would increase the effectiveness of the treatment of socially significant diseases such as stomach and intestinal cancer. Aim: To select the optimal dose with a subsequent assessment of the safety of iRAS when administered to patients with gastrointestinal tract tumors, including those with peritoneal carcinomatosis. Materials and methods: This was a prospective open-label non-randomized phase I study for the assessment of safety and tolerability, with an adaptive design and determination of the maximally tolerated dose of the iRAS. Three dose levels were used (0.45 mg/kg, 0.9 mg/kg, 1.8 mg/kg) according to the "3 + 3" scheme. The study included 11 patients after surgery for stomach or colorectal cancer. The patients were administered PIPAC therapy with iRAS twice with a 7-days interval. The study duration was 28 ± 1 days. During the study, the patient monitoring included physical examination, assessment of vital signs, electrocardiography and echocardiography, laboratory parameters (hematology, clinical chemistry, coagulation tests, and urine analysis). Results: The anti-tumor iRAS agent demonstrated satisfactory tolerability of all doses studied, including the maximal 1.8 mg/kg dose. Vital sign and laboratory abnormalities were clinically non-significant and did not require additional therapeutic interventions. Statistically significant abnormalities were registered for total protein (p = 0.00028), white blood cell counts (p = 0.007), lymphocyte counts (p = 0.0008), and a number of other blood parameters; however, most of these abnormalities were within the physiological normal ranges. Vital signs such as electrocardiography and echocardiography parameters remained stable throughout the entire follow-up period (28 days after administration of the drug). There were short-term rises in body temperature, minor pains in the postoperative scar area. Conclusion: This trial of safety and tolerability of iRAS showed that no cases of dose-limiting toxicity in the studied dose range. The 1.8 mg/kg dose can be recommended for further clinical studies.
{"title":"Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial","authors":"V. Bozhenko, S. Goncharov, E. Kudinova, Tatiana M. Kulinich, Elena A. Kukoleva, Mikhail S. Filippov, Anna F. Bykova, Oksana B. Knyazeva, Ilya A. Puchkov, V. A. Solodkiy","doi":"10.18786/2072-0505-2023-51-045","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-045","url":null,"abstract":"Background: Ras oncogene mutations leading to hyperactivation of the MAPK/ERK signaling pathway occur in 25% of all human tumors, and for gastrointestinal tumors, the frequency of Ras mutations amounts to 60%. The introduction of a Ras-GTPase inhibitor into clinical practice would increase the effectiveness of the treatment of socially significant diseases such as stomach and intestinal cancer. \u0000Aim: To select the optimal dose with a subsequent assessment of the safety of iRAS when administered to patients with gastrointestinal tract tumors, including those with peritoneal carcinomatosis. \u0000Materials and methods: This was a prospective open-label non-randomized phase I study for the assessment of safety and tolerability, with an adaptive design and determination of the maximally tolerated dose of the iRAS. Three dose levels were used (0.45 mg/kg, 0.9 mg/kg, 1.8 mg/kg) according to the \"3 + 3\" scheme. The study included 11 patients after surgery for stomach or colorectal cancer. The patients were administered PIPAC therapy with iRAS twice with a 7-days interval. The study duration was 28 ± 1 days. During the study, the patient monitoring included physical examination, assessment of vital signs, electrocardiography and echocardiography, laboratory parameters (hematology, clinical chemistry, coagulation tests, and urine analysis). \u0000Results: The anti-tumor iRAS agent demonstrated satisfactory tolerability of all doses studied, including the maximal 1.8 mg/kg dose. Vital sign and laboratory abnormalities were clinically non-significant and did not require additional therapeutic interventions. Statistically significant abnormalities were registered for total protein (p = 0.00028), white blood cell counts (p = 0.007), lymphocyte counts (p = 0.0008), and a number of other blood parameters; however, most of these abnormalities were within the physiological normal ranges. Vital signs such as electrocardiography and echocardiography parameters remained stable throughout the entire follow-up period (28 days after administration of the drug). There were short-term rises in body temperature, minor pains in the postoperative scar area. \u0000Conclusion: This trial of safety and tolerability of iRAS showed that no cases of dose-limiting toxicity in the studied dose range. The 1.8 mg/kg dose can be recommended for further clinical studies.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"101 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139615893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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