Course of COVID-19 in Patients with Inflammatory Bowel Disease: Regional Experience

Aim: to study the course of COVID-19 in patients with inflammatory bowel diseases (IBD) using the example of the region of the Republic of Tatarstan.Material and methods. The study included 101 patients diagnosed with IBD and COVID-19, who were observed in two infectious diseases hospitals in Kazan (Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan and City Clinical Hospital No. 7) and on an outpatient basis from April 2020 to March 2022. All patients underwent physical examination, laboratory and instrumental diagnostic methods, including a PCR test for SARSCoV-2. Chest computed tomography was performed in patients with clinical signs of moderate to severe COVID-19.Results. Ulcerative colitis (UC) was diagnosed in 60 (59.4 %) patients, Crohn's disease (CD) — in 41 (40.6 %) patients. The mean age of the patients was 41.0 ± 14.7 years, of which 59 (58.4 %) were men and 42 (41.6 %) were women. A comparative analysis of patients with and without IBD and CT-verified lung disease was carried out. It was found that the development of viral pneumonia was influenced by age over 55 years (39.2 ± 9.7 vs. 46.3 ± 10.6, p < 0.05), increased Body Mass Index (BMI) (23.1 ± 5.35 vs. 30.25 ± 6.17, p < 0.05), hypertension (6 (8.3 %) vs. 8 (27.6 %), p < 0.05), diabetes mellitus (2 (2.7 %) vs. 5 (17.2 %), p < 0.05), the use of corticosteroids in the treatment of IBD (8 (11.1 %) vs. 10 (34.5 %), p < 0.05). In a comparative analysis of patients with IBD and COVID-19 from the SECURE-IBD database and own data, it was found that the average age of patients was comparable (42.7 vs 41.0). At the same time, in our group of male patients, there were slightly more people with DM, increased BMI, and an active course of IBD. The proportion of hospitalized patients was higher. In our cohort, there were fewer patients receiving biological therapy, but more patients on 5-aminosalicylic acid (5-ASA) and systemic corticosteroids. At the same time, lethal outcomes were comparable.Conclusion. In patients with IBD, the development of viral pneumonia was influenced by known risk factors for COVID-19: age over 55 years (p < 0.05, odds ratio (OR) 3.153), increased BMI (p < 0.05, OR 1.667), hypertension  (p < 0.05, OR 2.724), diabetes (p < 0.05, OR 1.489), as well as the use of systemic corticosteroids (p < 0.05, OR 1.5)

Republican registry of primary immune deficiencies in the chuvash republic and description of postvaccinal immunity disorders in a pregnant patient with common variable immune deficiency

In recent years, primary immunodeficiencies have turned from the class of rare diseases to the category of more common disorders which may be encountered by doctors of any clinical discipline. The first case of primary immunodeficiency disorder (PID) in Chuvashia was detected in 1993. Since that time, the Department of Internal Diseases with the Course of Clinical Immunology at the I. Ulyanov Chuvash State University registered all the cases of PID diagnosed in the region, introducing them into the Republican Registry of PID. The study was aimed for searching epidemiological indexes, clinical and laboratory manifestations of PID in Chuvash region. The study was based on the patient data obtained by retrospective analysis of 85 case histories of PID patients, treated at different departments of the Republican Clinical Hospital, and the City Chuvash Pediatric Clinical Hospital of Public Health Ministry in 2000-2019, as well as on 49 outpatient records of the patients included into the Regional PID Registry. Various forms of PIDs were diagnosed according to the criteria developed by the European Society for Immunodeficiency and the Pan-American Group on Immunodeficiency (1999). The results of this study showed that the incidence of PID in the Chuivash Region is 3.4:100,000. The incidence of common variable immune deficiency (CVID), the most common form of PID in the region, was 1.58 per 100,000 population. The average age at the time of CVID diagnosis in Chuvash patients was 30.4±16.1 years, and the age of CVID debut was 11.3±15.0 years. The delay in proper diagnosis from the moment of clinical manifestation of CVID was, on average, 17.9 years in the region. At the time of CVID diagnosis, the patients showed marked decrease in the levels of 3 or 2 immunoglobulin classes (IgG and IgA), and T-helper cell contents (CD3+CD4+) in peripheral blood. Prevalence of selective IgA deficiency with сlinical symptoms was 0.83 per 100,000 population of the region, and the incidence of the asymptomatic form of this PID was 1 : 167. In patients with selective IgA deficiency, there were also disorders in the T cell system manifesting as decreased relative number of cytotoxic T-cells as well as elevated IgG and IgM levels. The age of diagnosis of X-linked agammaglobulinemia in the region was 3.5±3.0 years. In addition to disturbances of humoral adaptive immunity in children with this disease, a decrease in absolute T cell numbers was detected. In conclusion, the article describes disturbances of postvaccinal immunity in a pregnant patient with CVID, with asymptomatic clinical course, thus leading to false interpretation of the serological markers of TORCH infections and wrong strategy of pregnancy management

ОНКОЛОГИЧЕСКАЯ ЗАБОЛЕВАЕМОСТЬ В СИБИРСКОМ И ДАЛЬНЕВОСТОЧНОМ ФЕДЕРАЛЬНЫХ ОКРУГАХ

The purpose of the study was to analyze the cancer incidence among the population living in siberia and Russian Far East. material and methods. cancer incidence and mortality data collected from populationbased cancer registries of the Russian cancer statistics, covering the period 2005–2018, were used. the crude and age-standardized cancer incidence rates were analyzed. Results. During the study period, 1 336 260 new cases of cancer were diagnosed in the regions of siberia and Russian Far East. Of them, 77.2 % new cancer cases were registered in the siberian Federal District. the highest percent of increase in the number of cancer cases in the siberian Federal District was observed in the republics of Khakassia (84.8 %), tuva (61.9 %), Buryatia (52.8 %), and Krasnoyarsk Krai (82.4 %). In the Far Eastern Federal District, the highest cancer incidence rates were registered in the sakhalin Region (43.6 %) and Kamchatka Krai (41.8 %). the average age of patients in 2018 was 55.7 years (57.9 years for men and 53.7 years for women) compared to 57.4, 59.1 and 55.9 years, respectively in 2005. Lung cancer was the most commonly diagnosed cancer in men (19.5 %), whereas cancer of the female reproductive system was the most prevalent in women (38.4 %). the highest age-standardized cancer incidence rates in the siberian Federal District in 2018 were observed in the Irkutsk region, altai and Krasnoyarsk territories. In the Far Eastern Federal District, the highest agestandardized cancer incidence rates were observed in the sakhalin and Magadan regions. Conclusion. the number of new cancer cases and age-standardized cancer incidence rate were shown to increase in siberia and Russian Far East. the average age of men and women diagnosed with cancer decreased. the percent of increase in the age-standardized cancer incidence rate was higher in women than in men. Many of the most prevalent cancers were associated with the «westernized lifestyle» of developed countries.Цель исследования – анализ заболеваемости злокачественными новообразованиями (ЗНО) населения, проживающего на 20 территориях Сибирского и Дальневосточного федеральных округов (СФО и ДФО). Материал и методы. Использованы данные канцер-регистров территорий в 2005–2018 гг. и Федеральной службы государственной статистики РФ о численности и поло-возрастном составе населения. Проведен анализ экстенсивных, стандартизованных показателей. Результаты. За период исследования на территориях округов диагностировано 1 336 260 новых случаев ЗНО, из них 77,2 % – в СФО. Наибольший темп роста числа больных в СФО отмечался в республиках Хакасия (84,8 %), Тыва (61,9 %), Бурятия (52,8 %), Красноярском крае (82,4 %), в ДФО – в Сахалинской области (43,6 %) и Камчатском крае (41,8 %). Средний возраст заболевших в 2018 г. составил 55,7 года, для мужчин – 57,9, для женщин – 53,7 года, что меньше, чем в 2005 г. (57,4, 59,1 и 55,9 года соответственно). В структуре онкозаболеваемости мужского населения округов преобладал рак легкого (19,5 %), у женщин – опухоли органов репродуктивной системы (38,4 %). Наибольший стандартизованный показатель заболеваемости в 2018 г. в СФО регистрировался в Иркутской области, Алтайском и Красноярском краях, в ДФО – в Сахалинской и Магаданской областях. Заключение. В регионе наблюдался рост числа заболевших ЗНО и стандартизованного показателя заболеваемости. Средний возраст заболевших мужчин и женщин в регионе уменьшился («омоложение» рака). Темп прироста стандартизованного показателя ЗНО выше в женской популяции. В регионе отмечался рост показателей заболеваемости теми видами рака, одним из факторов риска которых является «западный» образ жизни

ЗЛОКАЧЕСТВЕННЫЕ НОВООБРАЗОВАНИЯ ВЕРХНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ У НАСЕЛЕНИЯ ТОМСКОЙ ОБЛАСТИ

Tomsk region refers to the areas of increased risk of malignancies, including laryngeal and upper respiratory tract cancers, which account for 2.0 % of all cancer cases. Approximately 83 new cancer cases (70 % in males) are annually diagnosed, with a tendency to increase. In 2014, the standardized incidence rate of upper respiratory tract cancer (URTC) was 7.7 per 100,000 men and women. The incidence rate was 6.7 times higher in men than in women. Laryngeal cancer was the most common malignancy in both men (67.7 %) and women (60.0 %). The age-standardized mortality rate of laryngeal cancer was 2.7 per 100,000 of population. Among patients registered at the end of 2014, 1.1 % patients were diagnosed with laryngeal cancer and 0.3 % with pharyngeal cancer. The laryngeal cancer incidence in the Tomsk region was lower than that in the Russian Federation as a whole. The rates of laryngeal and pharyngeal cancer detection at prophylactic medical examinations remain low (5.9 % and 1.5 %, respectively), and 1-year lethality rates are high (65.2 % and 28.6 %, respectively). Introduction of the program on pre-cancer and early laryngeal cancer detection into routine clinical practice allowed us to identify diagnostic errors in 16.3% of cases, verify laryngeal cancer and to form groups at high risk for laryngeal cancer in 20.6 % of cases

Down-regulation of TM4SF is associated with the metastatic potential of gastric carcinoma TM4SF members in gastric carcinoma

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to clarify the clinical significance of TM4SF members CD9, CD63 and CD82 in human gastric carcinoma.</p> <p>Methods</p> <p>By employing RT-PCR and immunohistochemistry, we studied the expression of CD9, CD63 and CD82 in 49 paired tissue specimens of normal gastric mucosa and carcinoma. All tissues were obtained from patients who underwent curative surgery.</p> <p>Results</p> <p>All normal gastric epithelium and gastric ulcer tissues strongly expressed transcripts and proteins of CD9, CD63 and CD82 as compared with corresponding controls. We found a significant correlation between CD63 mRNA level and different pM statuses (P = 0.036). Carcinomas in M0 stage revealed a stronger expression of CD63 than carcinomas in M1 stage. Expression of CD9 protein was found significantly stronger in pN0, pM0 than in advanced pN stages (P = 0.03), pM1 (P = 0.013), respectively. We found the relationship between CD63 expression, gender (p = 0.09) and nodal status (p = 0.028), respectively. Additionally, advanced and metastasized tumor tissues revealed significantly down-regulated CD82 protein expression (p = 0.033 and p = 0, respectively), which correlated with the tumor pTNM stage (p = 0.001).</p> <p>Conclusion</p> <p>The reduction of CD9, CD63 and CD82 expression are indicators for the metastatic potential of gastric carcinoma cells. Unlike their expression in other tumor types, the constitutive expression of CD63 may indicate that this factor does play a direct role in human gastric carcinogenesis.</p

КЛИНИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ТАРГЕТНОЙ ТЕРАПИИ В ОТНОШЕНИИ МЕТАСТАТИЧЕСКОГО РАКА ЛЁГКОГО С РАЗЛИЧНЫМИ ТИПАМИ ТРАНСЛОКАЦИЙ ГЕНА ALK

Introduction. Translocations of ALK receptor tyrosine kinase occur in approximately 5–9 % of lung adenocarcinomas. The use of ALK inhibitors usually results in the reduction of tumor size. Nevertheless, the extent and duration of response can vary significantly. The aim of the study is to summarize the available information on the predictive role of various types of ALK translocations in response to ALK inhibitors. Material and methods. The review presents the data from relevant laboratory and clinical studies published in PubMed database, as well as the authors’ own results. Results. A number of experiments on cell cultures have demonstrated that the structure of ALK fusion affects the properties of the resulting chimeric protein, in particular its stability and sensitivity to crisotinib action. The few available clinical trials, evaluating the effect of ALK inhibitors depending on the type of translocation, showed heterogeneous results. While some of them detected associations between the so-called «short» variants of EML4-ALK rearrangements and worse survival when using crisotinib in comparison with the EML4-ALK type 1 variant, the others failed to confirm these observations. The study of 64 Russian patients receiving ALK inhibitors also did not support the effect of different ALK translocation variants on progression-free survival or objective response rate. Conclusions. There is a diversity of reported associations, with none of them characterized by sufficient reproducibility. Current evidences do not support the predictive role of ALK variants.Актуальность. Транслокации рецепторной тирозинкиназы ALK встречаются примерно в 5–9 % аденокарцином лёгкого. Применение ингибиторов данной киназы, как правило, сопровождается выраженным ответом опухоли на лечение. Тем не менее глубина и длительность эффекта таргетной терапии варьируют от пациента к пациенту. Цель исследования – обобщить имеющиеся сведения о причастности различных типов транслокаций ALK к формированию ответа на лечение ингибиторами ALK. Материал и методы. В обзоре представлены результаты опубликованных в базе данных PubMed лабораторных и клинических работ, посвященных указанной проблеме, а также собственных исследований. Результаты. Эксперименты на клеточных культурах продемонстрировали, что структура транслокации ALK влияет на свойства химерного белкового продукта, в частности на его стабильность и чувствительность к воздействию кризотинибом. Немногочисленные выполненные до сих пор клинические исследования, оценивающие эффект ингибиторов ALK в зависимости от типа перестройки, имели разнородные результаты. Если в части работ были обнаружены ассоциации между «короткими» вариантами транслокаций EML4-ALK и худшими показателями выживаемости при использовании кризотиниба в сравнении с вариантом EML4-ALK 1 типа, то другие авторы не наблюдали таких закономерностей. Анализ итогов лечения ингибиторами ALK 64 российских пациентов также не обнаружил влияния типа транслокации на длительность периода до прогрессирования заболевания или частоту объективных ответов. Заключение. В изученных выборках пациентов отмечались различные по своему характеру ассоциации, ни одна из которых не отличалась воспроизводимостью. Таким образом, варианты перестроек ALK нельзя рассматривать в качестве предиктивного фактора ответа на ALK-специфическую терапию

KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer

<p>Abstract</p> <p>Background</p> <p>KAI1 was initially identified as a metastasis-suppressor gene in prostate cancer. It is a member of the tetraspan transmembrane superfamily (TM4SF) of membrane glycoproteins. As part of a tetraspanin-enriched microdomain (TEM), KAI1 inhibits tumor metastasis by negative regulation of Src. However, the underlying regulatory mechanism has not yet been fully elucidated. CUB-domain-containing protein 1 (CDCP1), which was previously known as tetraspanin-interacting protein in TEM, promoted metastasis via enhancement of Src activity. To better understand how KAI1 is involved in the negative regulation of Src, we here examined the function of KAI1 in CDCP1-mediated Src kinase activation and the consequences of this process, focusing on HIF-1 α and VEGF expression.</p> <p>Methods</p> <p>We used the human prostate cancer cell line PC3 which was devoid of KAI1 expression. Vector-transfected cells (PC3-GFP clone #8) and KAI1-expressing PC3 clones (PC3-KAI1 clone #5 and #6) were picked after stable transfection with KAI1 cDNA and selection in 800 <it>μ</it>g/ml G418. Protein levels were assessed by immunoblotting and VEGF reporter gene activity was measured by assaying luciferase activitiy. We followed tumor growth <it>in vivo </it>and immunohistochemistry was performed for detection of HIF-1, CDCP1, and VHL protein level.</p> <p>Results</p> <p>We demonstrated that Hypoxia-inducible factor 1α (HIF-1α) and VEGF expression were significantly inhibited by restoration of KAI1 in PC3 cells. In response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and the level of von Hippel-Lindau (VHL) protein was significantly increased. In an <it>in vivo </it>xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1α.</p> <p>Conclusions</p> <p>These novel observations may indicate that KAI1 exerts profound metastasis-suppressor activity in the tumor malignancy process via inhibition of CDCP1-mediated Src activation, followed by VHL-induced HIF-1α degradation and, ultimately, decreased VEGF expression.</p