Background:Methotrexate (MT) is a first-line drug in the treatment of rheumatoid arthritis (RA). The effectiveness and tolerability of the use of MT largely determines the prognosis of the course of the disease, the speed of achieving remission The development of hepatotoxicity (HT) is the most common adverse reaction, it is noted in 5-12.5% of cases and often requires the abolition of MT. In this regard, predicting the development of HT seems to be an important area of research.Objectives:to study genetic predictors of HT development in patients with RA using MT.Methods:44 patients with a reliable diagnosis of RA were included in study. All of the patients used MT at a dose of 15.0 (12.5-17.5) mg/week in combination with folic acid 3-5 mg / day outside of MT. The average age was 46.7 ± 12.3 years; females- 81.8% (n = 36); mail 18.2% (n = 8). The duration of RA is 5.3 ± 2.2 months. All patients were divided into two groups: the first study group (n = 17) included patients with RA who developed a HT reaction to MT, which required the abolition of MT; in the second- (n = 27) - comparison group - patients with good efficacy and tolerability of MT.Genotypes for polymorphic alleles were analyzed in all patients: C677T (rs1801133) and A1298C (rs1801131) of the methylenetetrahydrofolate reductase gene (MTHFR); 347C> G single-nucleotide polymorphism of the gene of aminoimidazole-carboxamidoriboside transformylase / inosine monophosphate cyclohydrolase (ATIC); c.80G> A locus of the SLC19A1 gene encoding the folate transporter membrane carrier protein.Groups were compared according to possible inheritance models: dominant, recessive, codominant. Statistical data processing was carried out using the SATISTICA 10.0 software package using descriptive and nonparametric statistics methods.Results:The frequency of occurrence of various mutations in genes that affect the metabolism of MT among patients with RA in the study and comparison groups are presented in table 1Table 1.The frequency of occurrence of various mutations in genes that affect the metabolism of MTGenetic optionStudy groupГТ+, n=17Comparison groupГТ <<->>, n=27MTHFR-A1298CCC56CA28AA1013MTHFR -C677TCC79CT817TT21347C>G ATICCC96CG619GG22SLC19A1c80A>GAA1122AG64GG00ГТ- hepatotoxicityWhen analyzing inheritance models, it was found that differences in hepatotoxicity for comparing genotypes (MTHFR-A1298C, MTHFR-C677T, SLC19A1c80A> G) were not statistically significant. A statistically significant increase in the risk of hepatotoxicity was found for dominant (2.18 (1.06-4.47), x2 = 4.38, p = 0.03) and codominant (0.42 (0.19-0.92), x2 = 5.23, p = 0.02) models for the 347C> G ATIC gene.Conclusion:Thus, an increase in the risk of hepatotoxicity for the dominant and codominant models for the 347C>G ATIC gene allows recommending genotyping of the alleles of this gene before MT administration in order to reduce the risk of hepatotoxic reactions.Disclosure of Interests:Natalia Martusevich Shareholder of: k, E. Aksenova: None declared, Katsiarina Gudkevich: None declared
Background:Avascular necrosis (AN) is a disease, which is the result of blood flow disturbance and necrosis of the bone tissue. It affects predominantly men of working age and steadily progresses to secondary osteoarthritis. AN is a multifactorial disease. In the context of vascular hypothesis it is of particular interest to evaluate homocysteine and its metabolism in patients with AN.Objectives:The aim of the present study was to evaluate some parameters of endothelial function in patients with AN of the femoral head or femoral condyles in order to determine possible treatment and prevention options.Methods:We included 53 patients with AN of the femoral head or femoral condyles into the study. The patients were aged 49 (35-62) years, 58,49% (n=31) were male. The inclusion criteria was diagnosis of AN confirmed by X-Ray, CT or MRI. The exclusion criteria were: traumatic AN, Legg-Calve-Pertes disease, connective tissue systemic diseases. We recruited 51 patients into the control group. The groups were comparable by age and gender. In order to analyse engothelial function in the groups we investigated the following serum parameters: homocysteine, vitamin B12, folate. In order to analyse the data obtained we used non-parametric statistics.Results:We determined a higher level of homocysteine in patients with AN (12,15 (7,55-14,60) vs. 8,18 (6,57-10,70) mcmol/l in the control group, p=0,04). Also we observed almost equal levels of vitamin B12 in patients with AN an in the control group (531,95 (340,80-793,55) vs. 532,75 (417,60-669,7) pg/ml, p=0,99). The level of folate was lower in the study group (5,66 (3,83-6,83) vs. 6,99 (5,02-10,38) ng/ml, p=0,01).Conclusion:The data obtained show that homocysteine level in patients with AN is higher. This can be a consequence of folate deficiency, which takes part in homocysteine metabolism. Therefore, homocysteine metabolism disturbances can lead to endothelial dysfunction, which results in cardiovascular events in the heart, brain, kidneys [1] as well as in the bone, according to the study results. Folate supplement is the possible way of AN treatment and prevention.References:[1]Nowroozpoor A, Gutterman D, Safdar B. Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review. Microvasc Res. 2021 Mar;134:104123. doi: 10.1016/j.mvr.2020.104123. Epub 2020 Dec 15. PMID: 33333140.Disclosure of Interests:None declared
Background:Avascular necrosis (AN) is a disabling disease affecting predominantly young men. It steadily progresses to secondary osteoarthritis. The rate of disability is high, because hip joint is most commonly affected by AN; moreover, the rate of bilateral hip joint involvement is also high. The key event in the pathogenesis of AN is circulation disorder which results in ischemia and, furthermore, death of bone tissue.Nowadays the data about lipid metabolism in patients with AN. Besides, there is contradictory data about the role of homocysteine in the risk of cardiovascular events. Based on these, it is topical to investigate lipid metabolism and endothelial function in patients with AN.Objectives:The aim of the present study was to investigate lipid metabolism and endothelial function in patients with different stages of AN in order to find risk factors for incidence and progression of this disease.Methods:We recruited 41 patients with AN of the femoral head or femoral condyles aged 51 (35-64) years, 56,1% (n=23) were male. The inclusion criteria was diagnosis of AN confirmed by X-Ray, CT or MRI. The exclusion criteria were: traumatic AN, Legg-Calve-Pertes disease, connective tissue systemic diseases. Also we divided patients into subgroups with early (39% (n=16)) and late (61,0% (n=25)) stages of AN.Patients of the control group (n=32) were comparable by age and gender. The data was proceeded using non-parametric and descriptive statistics. We evaluated the following parameters: homocysteine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, cholesterol ratio, apolipoprotein A1, apolipoprotein B.Results:In patients with AN we observed higher level of homocysteine (12,119 (7,771-14,38) vs. 7,911 (6,612-10,54) mcmol/l, p=0,05). The results are consistent with the data that higher homocyseine level is associated with higher risk for cardiovascular events (1). There is literature data about elevated homocysteine level in patients with AN, which was associated with lower levels of vitamin B12 and folic acid. Thus, interpretation of homocystene significance is more reliable in association with vitamin B12 and folic acid levels.Also, we observed that level of HDLP-C is higher in patients with early stages than in pate stages of AN (1,55 (1,31-1,57) vs. 1,23 (1,04-1,36) mmol/l, р=0,04). Thus, HDLP-C can be interpreted as a protective factor against contralateral joint involvement in AN patients. The data obtained is consistent with the existing data that HDLP-C lowers the risk for cardiovascular events.Conclusion:The data obtained indicate a significant role of dyslypidemia in the pathogenesis of AN in the context of vascular theory.References:[1]Steven G. Chrysant & George S. Chrysant (2018) The current status of homocysteine as a risk factor for cardiovascular disease: a mini review, Expert Review of Cardiovascular Therapy, 16:8, 559-565, DOI: 10.1080/14779072.2018.1497974.[2]Narayanan, A., Khanchandani, P., Borkar, R.M.et al.Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization.Sci Rep7, 10721 (2017).https://doi.org/10.1038/.Disclosure of Interests:Katsiarina Gudkevich: None declared, Natalia Martusevich Shareholder of: k, Elena Dashkevich: None declared
Background:Osteoarthritis (OA) is the leading cause of disability among all RMDs. Early diagnosis of OA is complicated. So, there is an absence of clear markers of the diagnosis of OA, and this issue is now being discussed.Objectives:The aim of this study is to examine relatively healthy individuals without symptoms in order to evaluate MR-markers of early OA of the knee.Methods:We included 29 relatively healthy individuals. 55,17% (n=16) were women. Median age was 35 (32-41) years. They didn’t have any complaints, according to the preliminary criteria of early OA, symptoms of OA (1), didn’t have any significant concomitant diseases and elevated ESR, CRP. The exclusion criteria were previous trauma, orthopedic surgery, X-Ray signs of OA. MRI was performed on 1,5 Tl Siemens Magnetom Essenza. WORMS-scale was used to evaluate the knee joint structures.Results:In all examined joints we observed small changes characteristic of symptomatic OA (osteophytes, cartilage damage etc.). In 4 knees we found undamaged cartilage (0 points). In 5 knees we observed cartilage damage >=4 points with marrow abnormality. In the Table 1 we present the frequency of any abnomaly (>=1 points) in each parameter present in examined joints. The most commonly asymptomatic changes were observed in the patellofemoral joint. Small osteophytes were the most common changes.Table 1.Number of examined knee joints with different anomalies according to WORMS (>=1 point).ParameterMFTJ (percent, total)LFTJ, (percent, total)PFJ (percent, total)S-region, (percent, total)Total, (percent, total)Cartilage19,44% (n=7)19,44% (n=7)75,00% (n=27)-83,33% (n=30)Marrow abnormality0,00%2,78% (n=1)0,00%13,89% (n=5)16,67%(n=6)Bone cysts0,00%0,00%0,00%0,00%0,00%Bone attrition66,67% (n=24)0,00%--66,67% (n=24)Osteophytes88,89% (n=32)86,11% (n=31)97,22% (n=35)-100,00% (n=36)Menisci0,00%2,78% (n=1)--2,78% (n=1)Ligaments----0,00%Synovitis----33,33% (n=12)Total––––100,00% (n=36)Besides, we calculated mean points in each parameter in the scale and compared it with the maximum score in this parameter (in percent). Table 2 shows the results. The most severe change was bone attrition.Table 2.Mean points of different WORMS parameters in examined knee joints.ParameterMFTJ (percent, total)LFTJ, (percent, total)PFJ (percent, total)S-region, (percent, total)Total, (percent, total)Cartilage1,30%1,02%7,64%-2,91%Marrow abnormality0,00%0,37%0,00%4,63%0,31%Bone cysts0,00%0,00%0,00%0,00%0,00%Bone attrition15,37%0,00%0,00%-1,75%Osteophytes6,59%5,48%8,33%-6,69%Menisci0,00%0,93%--0,46%Ligaments----0,00%Synovitis----12,04%Total----3,61%We didn’t observe asymptomatic lesions in the medial meniscus, marrow abnormality in MFTJ and LFTJ, subchondral cysts in any location, ligament lesions. Despite minimal osteophytes almost in all individuals, they didn’t have any clinical features of knee OA.Conclusion:MRI of the knee joints in the cohort of young relatively healthy individuals without clinical features of OA revealed irreversible structural changes characteristic of symptomatic OA. There is no association between symptoms and structural damage. Based on these, we can make an assumption about asymptomatic stage of OA. In order to distinguish between definitions of early asymptomatic OA as a disease onset and asymptomatic structural changes as reflection of metabolic disorders it is necessary to follow up and to perform an in-depth examination of these individuals.References:[1]Migliore, A., Scirè, C.A., Carmona, L.et al.The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology.Rheumatol Int37, 1227–1236 (2017).Disclosure of Interests:Natalia Martusevich Shareholder of: k, Svetlana Duben: None declared, Alexander Aleshkevich: None declared, Alena Dmitrieva: None declared, Tatsiana Bondar: None declared, Katsiarina Gudkevich: None declared
BackgroundAvascular necrosis (AN) represents a significant problem of modern rheumatology. The highest incidence of this disease is in able-bodied men. The risk of disability among patients with avascular necrosis of the femoral head (ANFH) is high, especially in case of bilateral process, as AN tends to progress steadily and results in osteoarthritis due to untimely diagnosis. Patients with AN can be affected by other coexistent diseases, that can influence the disease presentation and management.ObjectivesThis study aimed to analyse the prevalence and pattern of comorbidities in patients affected by ANFH and to determine if there is a differential pattern of comorbidities in patients with bilateral and unilateral ANFH.MethodsThis was a cross-sectional study, comprising 102 adult patients, aged 48,38–58 with a diagnosis of ANFH according to Ficat and Arlet criteria. Sociodemographic, anthropometric, clinical parameters of interest were collected from medical records. In order to characterise the burden of coexisting diseases or conditions Charlson Comorbidity Index was calculated. The data obtained were processed with STATISTICA 10.0 using descriptive and nonparametric statistics.ResultsAmong a total of 102 patients, a significant prevalence of comorbidities (86,27%) was found. 78,85% of all patients suffered from 2 or more coexistent conditions. The most prevalent comorbidities were: cardiovascular diseases (CVD) (53,92%), including hypertension (50,0%) and cardiosclerosis (34,31%), endocrine and metabolic disorders (66,67%), including hypercholesterolemia (65,70%) and obesity (32,35%), diseases of the digestive system (30,39%), dorsopathies (22,55%). The number of comorbidities was associated with age (ρ=0,42, p<0,001) and body mass index (ρ=0,29, p <0,001).In patients with bilateral (n=44), compared with those affected by unilateral ANFH (n=58), prevalence of younger age (43,5 (36–51) vs. 54,43–62 p<0,01) and male gender (odds ratio (OR) 2,99 (95% confidence interval (CI) 1,28–6,99), p<0,05) were detected. A history of (CVD) was more frequent in patients with unilateral ANFH (63,79% vs. 40,91%, OR 3,62 (95%CI 1,67–7,88), p <0,05), as well as hypertension (62,07% vs. 34,09%, OR 3,16 (95%CI 1,40–7,17, p <0,01). Patients with unilateral ANFH were more likely to have higher number of comorbidities (3,801,17–6,43 vs. 2,89 (0,73–5,05)) and Charlson Comorbidity Index (0,72 (0,43–1,47) vs. 0,52 (0,43–1,87)).ConclusionsANFH is associated with high prevalence of comorbidities, especially CVD.CVD, including hypertension, were more likely to be found in patients with unilateral ANFH, as well as higher comorbidity burden. It can be explained by the fact that patients with CVD received treatment according to national guidelines, including antihypertensive drugs, anticoagulants, statins, etc. This indicates that performing secondary prevention of CVD can be important in both CVD and ANFH, as such treatment can influence on intraosseous blood circulation in the contralateral joint.Reference[1] Valderas JM, Starfield B, Sibbal...
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