LECTURES
Atherosclerosis is the leading cause of cardiovascular disease among adults. The incidence of atherosclerosis increases significantly with age, which indicates the possible influence of aging mechanisms on the development of the disease, including changes in epigenetic factors caused by pathological activation of transposable elements. Triggers of atherosclerosis are also viral infections, which promote the expression of retroelements that stimulate the interferon response with the development of chronic inflammation. Activated retroelements also alter the regulation of immune system genes and epigenetic factors, including the pathological production of microRNAs and long non-coding RNAs. A promising direction for atherosclerosis treatment is the epigenetic impact on the expression of specific genes involved in the pathogenesis of atherosclerosis using small interfering RNAs. In this regard, the drugs inclisiran and olpasiran have undergone clinical trials and have shown their effectiveness. Therefore, it is important to search for new molecular targets in this direction, which can serve as transposons, which are sources of non-coding RNAs. Changes in the activity of retroelements during aging have a global regulatory effect on the functioning of the entire genome, contributing to the development of age-associated pathology. An analysis of the scientific literature made it possible to identify 29 microRNAs derived from retroelements, changes in the expression of which have been identified both during aging and atherosclerosis. These microRNAs can be used as tools for prolonging life and treating cardiovascular pathology. The results obtained also indicate that retroelements pathologically activated during aging cause the development of atherosclerosis.
REVIEW ARTICLE
The aim: To present the state-of-the-art of clinical features, differential diagnosis and treatment of IgG4-related sclerosing cholangitis.
Key points: IgG4-sclerosing cholangitis is a fibrotic inflammatory disease affecting the intrahepatic and extrahepatic bile ducts. The clinical features of IgG4-sclerosing cholangitis are similar to those of primary sclerosing cholangitis, bile duct cancer and pancreatic cancer. More than one third of patients with IgG4-sclerosing cholangitis undergo surgery. Currently, there are no specific and sensitive methods to diagnose this disease. Increased serum IgG4 levels are observed in many other diseases. A fourfold increase in serum IgG4 levels is a more reliable marker, but this feature is found in only a small percentage of patients. The imaging of bile ducts usually reveals segmental or extended strictures with prestenotic dilatation and wall thickening. Glucocorticosteroids are the first-line therapy for induction and maintenance of disease remission. More than a half of patients develop relapses. Several studies have found an increased risk of malignant tumors. This review describes the clinical, laboratory, and instrumental features of IgG4-sclerosing cholangitis. Comparative evaluation of diseases manifestations versus primary sclerosing cholangitis and cholangiocarcinoma is presented along with options of therapy, prognosis and outcomes of the disease.
Conclusion: IgG4-sclerosing cholangitis is a rare and difficult to diagnose disease that requires careful differential diagnosis with primary sclerosing cholangitis, bile duct cancer and pancreatic cancer. Despite its relatively benign course and efficacy of glucocorticosteroid therapy, the disease recurs frequently and has an unknown long-term outcome. Special attention is paid to the risk of malignant neoplasms in this group of patients, emphasizing the need for lifelong follow-up.
ORIGINAL ARTICLES
The aim - studying the dynamics of symptoms of post-COVID syndrome (depending on the results of depending on the results of the polymerase chain reaction for SARS-CoV-2) and the factors influencing it.
Materials and methods. A study is a cohort, observational longitudinal. Stage I: snapshot analysis of medical records of patients with COVID-19 disease history 12 months. (questionnaire for post-COVID syndrome, blood tests). Stage II: questionnaire repeat, disease history — 24 months. There were test (positive polymerase chain reaction, 138 people) and control (negative polymerase chain reaction, 87 people) groups. Statistical analysis: package Statistica 13.5.0.17.
Results. 1 year after COVID-19, the frequency of manifestations of post-COVID syndrome was (test vs control group): asthenia 63 % vs 64 %, decreased quality of life 59 % vs 56 %, respiratory syndrome 60 % vs 49 %, arthralgia 55 % vs 49 %, cardiac syndrome 47 % vs 46 % (the difference is not significant); symptoms are associated with female gender (r=0.231- 0.379), severity of COVID-19 (r=0.187-0.425), D-dimer (r=0.244-0.328). After 2 years, the frequency of symptoms was: asthenia 43 % vs 45 %, cardiac symptoms 23 % vs 15 %, respiratory symptoms 18 % vs 22 %, skin manifestations 8 % vs 12 %, decreased quality of life 7 % vs 9 %, the difference is not significant; symptoms are associated with age (r=0.208-0.402). During two years, symptoms have been correlating with platelets (r=-0.322-0.403), liver enzymes (r=0.216-0.298), blood lipids (r=0.188-0.257).
Conclusions. The severity of post-COVID syndrome does not depend on the results of the polymerase chain reaction for SARS-CoV-2. The frequency of cardiac and respiratory syndromes after 2 years decreases by 2-3 times; quality of life improves. Asthenia is the most long-term syndrome. Risk factors for post-COVID syndrome during the 1st year — severity of COVID-19, female gender, D-dimer level; from the 2nd year — age. For two years after COVID-19, monitoring of liver enzymes, lipids, and platelets is required.
The purpose of the study was to assess the contribution of kidney pathology to the estimated glomerular filtration rate and its prognostic value in elderly and senile patients.
Materials and methods. 472 elderly and senile age patients (241 women and 231 men, mean age 69.6±7.3 years) with stable cardiovascular diseases were examined. CKD was observed in 302 (63.9 %) elderly and senile patients. Estimated glomerular filtration rate (eGFR) was determined using the CKD-EPI equation (modified 2011). The contribution of kidney pathology (CKP) to eGFR was calculated by the difference between the “real” eGFR (calculated using the CKD-EPI, 2011 formula based on the “real” serum creatinine) and the predicted eGFR for a given age and sex (patent No. RU 2723748 C1). The follow-up period was 12 months. The primary endpoint was overall mortality.
Results. The CKP in eGFR in elderly and senile patients was 26.3 (14.9;35.7) %, increasing with the severity of CKD. The CKP in eGFR in elderly and senile patients with CKD did not differ depending on gender and age (p>0.05). The modified Charlson comorbidity index was higher in patients with CKD with CKP in eGFR more than 43.3 % compared to patients with The CKP in eGFR less than 43.3 (p = 0.004). The CKP in eGFR more than 43.3 % was associated with a 1-year risk of death in patients with CKD (OR 4.7; 95 % CI 1.99–10.9; p<0.0001). When assessing the prognostic value of CKP in eGFR, regardless of the CKD it was found that an increase CKP in eGFR more than 17.9 % was associated with a 1-year risk of death in elderly and senile patients with stable cardiovascular diseases (OR 2.47; 95 % CI 1.31–4.67; p=0.004).
Conclusion. The CKP in eGFR in elderly and senile patients with CKD and stable cardiovascular comorbidity increases with the severity of CKD and does not depend on gender and age. In elderly and senile patients with stable cardiovascular diseases, the CKP in eGFR has prognostic advantages when assessing annual mortality compared to eGFR assessment using the CKD EPI formula (2011).
Background: Antiviral therapy with nucleos(t)ide analogs for chronic hepatitis B is aimed at preventing disease progression and the development of complications. However, current therapies do not allow elimination of hepatitis B virus, and long-term treatment is required to maintain clinical effect in most patients. In this regard, the study of associated factors with the efficacy of antiviral therapy of nucleos(t)ide analogs is actual.
Aim: To evaluate efficacy and identify predictors of response to antiviral therapy with nucleos(t)ide analogs in patients with chronic hepatitis B.
Materials and methods: This retrospective-prospective observational study included 71 patients with chronic hepatitis B who received nucleos(t)ide analogs at the Center for Diagnosis and Treatment of Chronic Viral Hepatitis from 2008 to 2023. The efficacy of antiviral therapy with nucleos(t)ide analogs was evaluated after 24, 48, and 96 weeks of drug intake. The prognostic factors associated with obtaining a virologic response after one year of antiviral therapy and with achieving a significant decrease in liver density by transient elastometry were examined. Results: The virologic and biochemical response rate increased as antiviral therapy continued, and after 96 weeks of taking nucleos(t)ide analogs was 92.6 %. Baseline viral load level was an independent prognostic factor for achieving aviremia after 48 weeks of antiviral therapy (p=0.022). HBsAg clearance was observed in 2 (2.8 %) patients, HBeAg clearance — in 5 HBeAg-positive patients. On nucleos(t)ide analogs treatment there was a significant decrease of liver fibrosis measured by transient elastometry, and a high level of transient elastometry at the beginning of antiviral therapy is a factor associated with a significant decrease in liver density (by 25 % or more) (p=0.022).
Conclusion: Antiviral therapy with nucleos(t)ide analogs has demonstrated high efficacy in suppressing hepatitis B virus replication, normalizing aminotransferase activity, and reducing liver fibrosis. Baseline viral load and transient elastometry levels are the most important prognostic factors associated with the efficacy of antiviral therapy with nucleos(t)ide analogs.
Despite significant progress in the field of prevention, early diagnosis and antibacterial therapy, community-acquired pneumonia still retains the status of not only the most common among acute infectious diseases, but is also a frequent source of sepsis, which greatly increases the likelihood of death in this group of patients. The purpose of the study was to perform a comparative analysis of clinical and laboratory parameters and assess the nature of their changes in the first 48 hours from the moment of verification of sepsis that developed against the background of pneumonia in patients of the therapeutic department, depending on the outcome of hospitalization.
Clinical groups and research methods. A retrospective comparative study was carried out, which included, using a continuous sampling method, patients with sepsis that developed against the background of pneumonia in patients hospitalized in therapeutic clinics of the Federal State Budgetary Educational Institution of Higher Education Siberian State Medical University of the Ministry of Health of Russia in the period from 01/01/2019 to 04/30/2023. In total, the study included 40 patients of both gender, followed by division into two comparison groups depending on the outcome of hospitalization (discharge from hospital or death) for the dynamic assessment of clinical, anamnestic and laboratory parameters in the early stages of the development of a septic condition (the first 48 hours) in order to determine their relationship with the outcome of hospitalization.
Results. All patients were divided into 2 groups. The first group (n=17, 42.5 %) consisted of patients with a favorable outcome of hospitalization (recovery), the second group (n=23, 57.5 %) consisted of patients with a fatal outcome. At the time of verification of sepsis, patients with a favorable outcome had a significantly lower SOFA score (3 (2; 6) points) than patients with a fatal outcome (6 (5; 7) points), p = 0.037. The change in urea concentration in the first 48 hours from the moment of verification of sepsis, which in the group of survivors was -1.3 (-4.4; 1.99) mmol/l, and in the group of deceased 5.5 (-1.5; 12. 2) mmol/l, p=0.020. In the group of deceased patients, 8 people (34 %) at the time of verification of sepsis had a combination of hypotension (<90/60 mm Hg) and serum lactate >5 mmol/l. In the survivor group, hypotension was observed in only 2 people (11 %), and lactate levels in these patients were in the range of 4.5- 4.6 mmol/l. At point 1, the indicators of immature granulocytes were not statistically significantly different between surviving and deceased patients (1.2 (0.7; 2.1)% vs 0.8 (0.6; 1.5)%, respectively, p>0. 05). After 48 hours, the level of immature granulocytes increased in surviving patients to 1.5 (1; 3.2)% and, conversely, decreased to 0.65 (0.45; 1.45)% in the group of deceased patients, and the difference in these indicators between groups became statistically significant, p <0.05.
Conclusion. Thus, in patients with sepsis against the background of severe pneumonia, the mortality rate was 57.5 %. In order to identify groups at high risk of death due to sepsis due to pneumonia, in addition to the SOFA scale, dynamic monitoring of biomarkers such as urea, lactate, immature granulocytes and reticulocytes should be carried out in the first 48 hours from the moment of verification of the septic state.
Цель исследования. Изучить ассоциацию клинико-диагностических показателей кардиоваскулярной токсичности у пациентов с неходжкинскими лимфомами, находящихся в процессе программной противоопухолевой иммунохимиотерапии.
Материалы и методы. Проспективно было отобрано 72 пациента с подтвержденным диагнозом «индолентная неходжкинская лимфома», которым показано проведение противоопухолевого лечения по схеме R-CHOP. Пациенты были обследованы в два визита: V1 — на старте и V2 — после 6 курсов терапии. В процессе наблюдения пациенты были поделены на 2 группы: основную — с признаками сердечно-сосудистой токсичности (21 пациент, 16 (76,2 %) мужчин, средний возраст 55,2 (9,8) лет) и контрольную — без нее (51 пациент, 21 (41,2 %) мужчин, средний возраст 53,7(13,6) лет. Кардиоваскулярная токсичность верифицировалась на основании сочетания жалоб с изменениями в сократительной способности миокарда: снижения фракции выброса левого желудочка >10 % от исходного уровня или в абсолютном выражении менее, чем 53 % и/или снижения продольной систолической деформации левого желудочка >12 % от исходного уровня.
Результаты. По окончанию основного лечения в обеих группах наблюдения отмечено статистически значимое увеличение QTc. Значимо менялось значение глобальной продольной систолической деформации левого желудочка у пациентов основной группы при одномоментном отсутствии ключевых сдвигов в отношении фракции выброса левого желудочка. Наиболее чувствительным лабораторным показателем кардиоваскулярной токсичности оказался NTproBNP, концентрация которого статистически значимо увеличивалась у основной группы пациентов.
Заключение. Расширение минимальной диагностической панели и комплексный подход к верификации кардиоваскулярной токсичности у пациентов онкогематологического профиля, получающих потенциально токсичную для сердечно-сосудистой системы терапию, позволит существенно улучшить показатели эффективности работы ключевых служб здравоохранения, снизить финансовые расходы на нивелирование осложнений и повысить качество жизни пациентов.
Materials and Methods. A retrospective study of 785 medical records of patients hospitalized between 05.2020 and 12.2020 with a diagnosis of moderate to severe new coronavirus COVID-19 infection was performed in phase I. The study was conducted. The primary objective was to evaluate clinical symptoms with a focus on detecting gastroenterologic manifestations of COVID-19. After discharge from the Covid hospital in 3, 6 and 12 months, a telephone questionnaire was conducted using a specially developed questionnaire by the staff of the Department of Internal Medicine of the FSBEU VO BSMU of the Ministry of Health of the Russian Federation to identify gastroenterological symptoms, as well as using the standard questionnaire for the assessment of gastrointestinal symptoms GSRS (Gastrointestinal Symptom Rating Scale) and the Bristol Stool Assessment Scale. 247 respondents took part in the survey, after which they were divided into 3 groups according to the criterion of presence and duration of gastrointestinal symptoms. Group 1 — patients with persisting gastrointestinal symptoms in the period from 4 to 12 weeks (ongoing symptomatic COVID) — 30 people; Group 2 — patients with duration of gastrointestinal symptoms more than 12 weeks (post-COVID syndrome) — 75 people. The control group (group 3) consisted of 151 patients who had survived COVID-19 without the development of postcoviral syndrome. At stage II, serum concentrations of immunologic markers (interleukins 4, 6, 8, 18; rheumatoid factor, antibodies to DNA,) were studied in each group of patients.
Results. There was a statistically significant increase in the mean age in group 1 and group 2 patients (p=0.02*10-4 and p=0.01*10-9), as well as in the duration of hospitalization in group 1 patients compared to the control group (p=0.04). Women predominated in both groups 1 (p=0.01) and 2 (p=0.002). The time of outpatient treatment before hospitalization averaged 8.1 days. In both groups of patients there was a statistically significant increase in IL-18 level (p=0,095; p=0,88*10-9), in group 2 there was an increase in rheumatoid factor level (p=0,044) in comparison with the control group. A statistically significant increase in IL-6 levels was also revealed in both studied groups in comparison with the control group (p=0,020; p=0,000017), while the mean values were within the reference intervals.
Conclusions. Thus, patients who have had moderate to severe COVID-19 are susceptible to the development of post-Covid syndrome, including gastroenterological manifestations. For the first time, an elevated level of IL-18 was detected in this category of patients, which can serve as both a diagnostic marker and a potential target for targeted therapy.
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