[Long-term use of glucocorticoids in patients with active rheumatoid arthritis: therapeutic "freeze frame"].

BACKGROUND: In Russia, as well as throughout the world, the use of glucocorticoids (GC) in the treatment of rheumatoid arthritis (RA) is widespread, often going beyond the recommendations for both duration and dose regimen, which makes it relevant to study the long-term consequences of such a "wrong" (EULAR, 2022) use of GC in RA therapy. MATERIALS AND METHODS: Of 1143 patients with active RA (ACR/EULAR 2010), two groups were formed: A (n=782) RA patients with more than 6 months of experience with systemic GC; group B (n=245) - no experience of taking GC. The cumulative disease index (CIRS) was used to assess the comorbidity profile. RESULTS: Patients in group A were older (p<0.0001), with a longer duration of RA (p=0.0004) and more often with IV radiological stage (p=0.02). With comparable (DAS28) RA activity, the D2T variant of RA was more often detected in them (p=0.036). RA therapy in group A was characterized by a large number of used disease-modifying anti-rheumatic drugs (p=0.0003), more frequent development of methotrexate-induced hepatitis (p=0.03). In group A, the time interval between the onset of RA and the initiation of biological therapy was longer (p=0.0001) and directly correlated with the duration of GC therapy (Rs=0.38) with a comparable qualitative structure of the used b/tsDMARDs. In the same group, tuberculosis, hypertension, chronic kidney disease, cataract and osteoporosis (p<0.05) and its complications were diagnosed significantly more often with a comparable frequency of cardiovascular disease, diabetes, and gastrointestinal lesions. In group A, a higher CIRS multimorbidity index was detected, and the CIRS severity index was lower than in group B (p<0.05). CONCLUSION: Long-term use of GC did not lead to a decrease in disease activity, inhibition of radiographic progression, delayed the timely administration of b/tsDMARDS and was accompanied by an increase in the multimorbid load.

[Difficult-to-treat rheumatoid arthritis in real clinical practice. Preliminary results].

AIM: To compare the features of the course of the disease and the therapy in rheumatoid arthritis (RA) patients who meet the criteria of difficult-to-treat RA (D2T). MATERIALS AND METHODS: The study included 505 RA patients (ACR/EULAR 2010). Rheumatologist experts discussed all patients, since the treatment of RA ware perceived as problematic and/or insufficient. All patients had at least one of the following signs: the activity of the disease is no lower than moderate; the inability to reduce the dose of glucocorticoids to low; rapid radiological progression; RA symptoms causing a decrease in quality of life. The D2T group included 35 patients with true inefficiency or intolerance of two or more of bDMARDs/tsDMARDs of different mechanism of action. The control group (K) included patients with RA who already had experience of taking at least one class of bDMARDs/tsDMARDs (n=291). RESULTS: On average, every 15 patients (7%) with RA met the EULAR criteria for D2T. The median age of patients in the D2T group was 45 years, which is less than in K (Me 54 [43; 62] years; p=0.046). The duration of RA in both groups was comparable. The severity of articular destruction in D2T was higher than in K (stage IV in 40% and 23%, respectively). Positivity for the RF and ACPA in D2T was less common than in K (60% and 85.9%; 60% and 76.6%, respectively). The presence of systemic manifestations of RA was more typical for K than for D2T (28.6% and 63%, p=0.0001). In the group of D2T patients, the number of previously taken DMARDs was higher than in K (p=0.002). Methotrexate was more often prescribed as the first DMARDs in both groups (in 62.9 and 65.7%, respectively). Initiation of bDMARDs/tsDMARDs therapy in D2T was more often performed by TNF-a inhibitors (OR 2.8; p=0.003) and co-stimulation blocker abatacept (OR 4.6; p=0.004), and in control by B-cell inhibitor rituximab (OR 6.9; p0.0001). CONCLUSION: The results of this study suggest that in Russia, as well as abroad, the principle of RA treatment treat to target has not yet become widespread, and the development of adequate therapy takes too much time.

[The role of the angiotensins in the pathogenesis of inflammatory joint disease].

The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.

Gas-phase treatment of polyethylene terephthalate waste in nitrating atmosphere for recycling purposes.

The paper describes a new method of waste polyethylene terephthalate (PET) recycling based on gas-phase treatment of the material in nitrating atmosphere. It was found that PET samples kept in the nitrating atmosphere (obtained by vaporizing 12 mol L-1 HNO3) at a temperature of 403-463 K (130-190 °C) for 5-24 h dissolve in 0.5 mol L-1 NaOH, in contrast to the untreated PET samples. Ozonation of the obtained alkaline solutions leads to a complete decomposition of the organic compounds present in the solutions. The resulting PET decomposition degree is higher than 99.9 % irrespective of the plastic color. In addition, the possibility of terephthalic acid recovery from the alkaline solutions of the conversion products was shown.

The Dependence of the Mutagenic Effect on the Dose of X-Ray Irradiation in an In Vivo Experiment on Female (CBA×C57Bl/6)F1 Mice.

We studied the mutagenic effect of X-ray irradiation in doses of 0.5, 1, and 1.5 Gy on female (CBA×C57Bl/6)F1 mice. The mutagenic effect (assessed by the parameter "frequency of bone marrow polychromatophilic erythrocytes with micronuclei") linearly depended on the dose of X-ray irradiation in the range of up to 1 Gy and reached the plateau at 1.5 Gy. The fraction of polychromatophilic erythrocytes was 45, 45, and 46% under control conditions (without exposure) and exposure to the irradiation in the doses of 0.5 and 1 Gy, respectively. Irradiation in a dose of 1.5 Gy induced a slight inhibition of erythropoiesis. These data confirm the hypothesis on possible death of highly aberrant erythrocyte precursors after irradiation in high doses.

[Slow Formation and Degradation of γH2AX Foci in Human Skin Fibroblasts Exposed to Low-Dose X-Ray Radiation].

It was shown that the kinetics of changes of γH2AX foci number (marker of DNA double-strand breaks) in human skin fibroblasts after exposure to low doses of X-ray radiation (20, 40 and 80 mGy) differs from that observed after exposure to medium-low doses (160 and 240 mGy). After exposure to 160 and 240 mGy the highest number of γH2AX foci was detected at 30 min after exposure (first experimental point) and further their decrease was observed. At the same time we observed a fast phase of repair (upto 4 h), in which there was a decrease of the foci amount to ~50-60% and a slow phase of repair (from 4 h to 24 h). After 24 h only ~3-5% of the foci amount observed at 30 min after irradiation was left. After exposure to low doses, the foci number did not decrease during 2 h and even 24 h after exposure their amount was ~25% from that observed at maximum points (1 h after irradiation at 40 and 80 mGy and 2 h after irradiation at 20 mGy).

[Rheumatic diseases and multimorbidity].

In the past decade, investigators' undeniable and justified interest has not been fading in comorbidities in the presence of rheumatic diseases. The terms "comorbidity" and "multimorbidity" are frequently and not always consciously used as interinterchangeable, confusing the terminology and accordingly the elaboration of strategies for further researches. The concepts "(co-occurring disease" and "multimodality" are not mutually exclusive or contradictory, but these should be considered from another point of view than "comorbidity". The problem of multimorbid disease is the rule rather than the exception for clinicians treating primarily "typical" rheumatic patients. Recent researches could outline a few key areas for further study of the concept of multimorbidity in rheumatologic practice, which will be able to turn the international research community from rheumatic disease to the patient as a whole.

[Hemophagocytic syndrome in a patient with adult-onset Still's disease: diagnostic problems].

Hemophagocytic syndrome (HPS) is a rare life-threatening condition caused by massive cytokine release from activated macrophages and lymphocytes. The paper depicts the development of HPS in different infections, malignancies, and autoimmune diseases. It describes a clinical case of hemophagocytic syndrome in a 63-year-old female patient with adult-onset Still's disease and high fever accompanied by neutrophil leukocytosis and a drastic left leukocyte count shift, high procalcitonin levels, hepatosplenomegaly, edematous syndrome, and progressive multiple organ dysfunction with the development of disseminated intravascular coagulation and adult respiratory distress syndrome. The diagnosis of HPS was established according to the diagnostic criteria and verified by autopsy: phagocytes in liver and lung tissues.

Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients.

Ankylosing spondylitis (AS) is commonly characterized by clonal expansions of T cells. However, these clonal populations are poorly studied and their role in disease initiation and progression remains unclear. Here, we performed mass sequencing of TCR V beta libraries to search for the expanded T cell clones for two AS patients. A number of clones comprising more than 5% of the corresponding TCR V beta family were identified in both patients. For the first time, expanded clones were shown to be stably abundant in blood samples of AS patients for the prolonged period (1.5 and 2.5 years for two patients, correspondingly). These clones were individually characterized in respect to their differentiation status using fluorescent cell sorting with CD27, CD28, and CD45RA markers followed by quantitative identification of each clone within corresponding fraction using real time PCR analysis. Stable clones differed in phenotype and several were shown to belong to the proinflammatory CD27 - /CD28 - population. Their potentially cytotoxic status was confirmed by staining with perforin-specific antibodies. Search for the TCR V beta CRD3 sequences homologous to the identified clones revealed close matches with the previously reported T cell clones from AS and reactive arthritis patients, thus supporting their role in the disease and proposing consensus TCR V beta CDR3 motifs for AS. Interestingly, these motifs were also found to have homology with earlier reported virus-specific CDR3 variants, indicating that viral infections could play role in development of AS.

Effective kinematic viscosity of turbulent He II.

The temperature dependence of the effective kinematic viscosity of turbulent He II, nu(eff)(T) , is deduced from second sound attenuation data using the late stage of decay of thermally induced counterflow He II turbulence in two channels of square cross section. It is shown to qualitatively agree with the published data for nu(eff)(T) calculated based on experiments on decaying-grid-generated He II turbulence [Niemela, J. Low Temp. Phys. 138, 537 (2005)]. Corrections to these data due to the "sine squared" law that describes attenuation of the second sound wave propagating along an arbitrary direction with respect to the direction of the core of a quantized vortex in turbulent He II are discussed and applied.

Depolarization of decaying counterflow turbulence in He II.

We present experimental evidence backed up by numerical simulations that the steady-state vortex tangle created in He II by heat-transfer counterflow is strongly polarized. When the heater that generates the counterflow turbulence is switched off, the vortex tangle decays, the vortex lines randomize their spatial orientation and the tangle's polarization decreases. The process of depolarization slows down the recovery of the transverse second sound signal which measures the vortex line density; at some values of parameters it even leads to a net decrease of the amplitude of the transverse second sound prior to reaching the universal -32 power temporal law decay typical of classical homogeneous isotropic turbulence in a finite-sized channel.

[Morton disease].

The author presents a review of 17 Russian and foreign sourses dedicated to Morton's disease and describes a clinical case.

Decay of counterflow He II turbulence in a finite channel: possibility of missing links between classical and quantum turbulence.

Decay of He II counterflow turbulence generated by applying a heat pulse to the closed end of a circular channel is investigated using second sound attenuation. Several orders of magnitude of decaying vortex line density display various regimes, starting with the inverse time decay predicted by Vinen towards distinct classical t(-3/2) power law occurring after saturation of the energy containing length scale by the size of the channel. The decaying counterflow turbulence displays a surprisingly close resemblance to recently reported decaying grid turbulence in He II, and both of them appear closely linked to classical grid generated turbulence.