The role of timely rheumatoid arthritis treatment effectiveness control

Background. Regular assessment of rheumatoid arthritis (RA) activity is a key factor in therapy effectiveness improving. Aim. To prove that timely RA treatment control recommended by modern guidelines improves outcomes and reduce disability in real clinical practice. Materials and methods. Fourty patients with RA hospitalized at the University Clinical Hospital from January 2021 to January 2023 were included into a retrospective single-center study and divided into 2 groups. In the first group, RA activity was monitored after 3, 6, and 12 months, with therapy adjusted if necessary. In the second group, monitoring of RA activity was carried out after 12 months. The patients underwent clinical, laboratory and instrumental examinations (Tender Joint Count (TJC) and Swollen Joint Count (SJC), common blood test with differential white blood cell count, ESR, biochemical blood test, CRP, RF, ACCP, hands, feet and chest X-ray, ECG). RA activity was assessed using DAS28, CDAI, SDAI indices in both groups. Results. RA activity control after 12 months in patients of the first group regularly observed by a rheumatologist was better than in patients of the second group, who visited rheumatologist again only in 12 months. DAS28 decreased significantly, from 4.71±0.80 to 3.08±0.70 in the group with regular monitoring during the observation period. Remission or low activity was achieved by 75% of patients (5% remission and 70% low activity). Less dynamics was registered in patients of the second group: the initial DAS28 was 4.50±0.74, DAS28 after 12 months was 4.36±0.64, which corresponds to moderate activity. Low activity was achieved in 15% of patients, remission was not achieved in any patient. Conclusion. Strict adherence to the recommended terms for disease activity monitoring is necessary for successful RA treatment in real clinical practice

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

The susceptibility of human melanoma cells to infection with the Leningrad-16 vaccine strain of measles virus

Oncolytic viruses, including live attenuated measles virus (MV) vaccine strains, have recently been shown as promising therapeutic agents against human malignancies. In this study, the oncolytic potential of the attenuated vaccine strain Leningrad-16 (L-16) of MV was evaluated in a panel of human metastatic melanoma cell lines. The L-16 measles virus was shown to replicate within melanoma cells mediating direct cell killing of tumor cells, although all melanoma cell lines varied in regard to their ability to respond to L-16 MV infection, as revealed by the different pattern of the Interferon Stimulated Gene expression, cytokine release and mechanisms of cell death. Furthermore, the statistically significant L-16 measles virus related tumor growth inhibition was demonstrated in a melanoma xenograft model. Therefore, L-16 MV represents an appealing oncolytic platform for target delivery of therapeutic genes along with other attenuated measles virus strains. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

AUTOPHAGY REGULATION BY RUBELLA VIRUS

Aim. Some viruses can subvert host defense mechanism, autophagy, to their own benefit. We analysed the effect of Rubella virus (RV) infection on autophagy in human alveolar epithelial cells A549. Materials and methods. Cells were infected with the wild type and lab-attenuated strain, C-77w and C-77a, respectively, with a multiplicity of infection of 1.0, in parallel, the expression level of genes encoding Beclin1, Atg5, Rab7, and p62 (SQSTM1) proteins participating in different steps of autolysosome formation was measured. To investigate the role of autophagy on RV replication cycle, we measured the amount of infectious RV particles, together with the viral RNA in supernatants and cell lysates, after incubation of A549 cells with wild type or attenuated strain in the presence of the autophagy inhibitor, Bafilomycin A1, or inducer, Rapamycin. Results. The significant increase in Beclin1 and Atg5 gene expression at 24-48 (for the wild type) and 24-72 (for the attenuated type) hours after infection was observed, while significant induction of either Rab7 or SQSTM1 gene expression was not noticed. This effect was correlated with more delayed increase of IFNβ expression and IFNβ-mediated pro-apoptotic gene expression leading to apoptotic cell death 72-96 hours after infection. Moreover, Bafilomycin A1 diminished the RV infection non significantly, as evidenced by the RT-qPCR and plaque assay, while Rapamycin increased the amount of infectious RV particles released by the infected cells more dramatically with wild type comparing with attenuated strain. Conclusion. Thus, we hypothesized that RV can use an antiviral mechanism to prevent degradation and ensure its replication, differentially regulating the process of autophagy, by stimulating the initiation and suppression of later steps