Порушення пуринового обміну у хворих на подагру: зв'язок з дисадипокінемією

Aim of the research was the study of the features of the exchange of urea acid in patients with gout and assessment of their connection with disadypokinemia.Materials and methods. In the study took part 151 patients with gout and 31 person from control group. The level of uric acid in the serum of blood and urine was determined by the biochemical method, the level of leptin and adyponectin by the enzyme-linked immunosorbent assay. The evaluation of the correlation between uric acid metabolism and disadypokinemia was performed using the Pearson correlation coefficient. Student's t-criterion was used to assess the differences between the groups.Results. It turned out that in patients with gout there is a significant increase in the level of UA in the blood, lower clearance of UA and low fractional excretion compared with the control group. Disadypokinemia was also more pronounced in the group of patients with gout. In subjects with severe disadypokinemia, higher values of hyperuricemia were observed, a significantly lower excretion of UA with urine, reduced clearance and fractional excretion of UA.Conclusions. Patients with gout have a rise in uricemia with reduced clearance and fractional excretion of UA. An associative connection between adypokin status in patients with gout and urinary acid metabolism was establishedМетою роботи було вивчення особливостей обміну сечової кислоти у хворих на подагру чоловіків, що включає визначення рівня сечової кислоти сироватки крові, кліренс, добову екскрецію та фракційну екскрецію сечової кислоти, а також оцінка зв’язку між цими показниками з дисадипокінемією. Отримані результати демонструють відмінності між адипокіновим статусом хворих та контрольною групою; наявність зв’язку між дисадипокінемією та обміном сечової кислоти у хворих на подагр

Рівні лептину крові у хворих на остеоартроз: зв’язок з клінічними проявами захворювання

Aim of the work: study of the content of leptin in the serum of patients with OA and the study of relationships with clinical manifestations and functional status of patients.Objects and methods: The determination of blood serum leptin levels and for the evaluation of the Lequesne index, HAQ, and KOOS was performed on 71 female with knee joints OA and 32 healthy women in control group.Results. There was a significant relationship between serum leptin levels and the HAQ scale (p=0.026) and significant differences in the level of leptin in the X-ray stage of OA (p=0.043). An association of excess body weight with an increase in the level of serum leptin in the level of the tendency is established.Conlusions: A detailed analysis of the level of leptin in relation to clinical and demographic indicators, clinical manifestations and functional status of patients with OA revealed a significant difference in the level of leptin in the context of the X-ray stage of OA. A reliable link between the level of leptin and the functional status of patients with HAQ was found. In addition, the association of excess body weight with the increase in the level of serum leptin in the bloodstream was observed at the level of the trend.Стаття присвячена дослідженню зв’язку рівня лептину з клінічними проявами захворювання у хворих на остеоартроз та вивченню їх клініко-патогенетичних взаємовідношень, що є пріоритетним напрямком дослідження в ревматології. Нами показано наявність достовірного зв’язку між рівнем лептину сироватки крові і шкалою HAQ (р=0,026) та достовірних відмінностей рівня лептину в розрізі рентгенологічної стадії ОА (р=0,043). Встановлена асоціація надлишкової маси тіла з підвищенням рівня лептину в сироватці крові на рівні тенденці

Рівень галектину-3 в сироватці крові хворих на остеоартроз колінних суглобів: зв’язок з перебігом захворювання

Aim of the work was to study the level of galectin-3 in serum in patients with osteoarthrosis of knee joints and to evaluate its association with the course of the disease.Materials and methods. We examined 141 patients with osteoarthrosis (OA) of knee joints (76.6% of women), an average age of 58.4 ± 7.91 years, a disease duration of 10.5 ± 6.50 years, an II-III radiological stage. 33.3% of patients had a combination of OA knee and hip joints. Diagnosis of OA was established on the basis of criteria ACR 1991 and recommendations EULAR (2010). The Lequesne algo-functional index, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) were determined. Functional disorders were evaluated by the Health Assessment Questionnaire (HAQ). The content of galectin-3 in the blood was determined by the enzyme-linked immuno sorbent assay.Results. It has been established that in 75% of patients with OA of knee joints aberrant levels of galectin-3 in the blood are detected, including 44% of subjects with a registered high level of the index (>15.8 ng/ml). The weak associative relationships between the level of galectin-3 and the age of patients and the duration of OA were established. Among patients with aberrant levels of galectin-3, persons with severe clinical manifestations of OA appeared more often. The increase in the level of galectin-3 was associated with a significant increase in the pain syndrome and the deterioration of physical function by the indexes of Lequesne, WOMAC, KOOS, HAQ.Conclusions. In patients with OA, the increase in the production of galectin-3 is a factor in the deterioration of the clinical course of the disease, the increase in pain syndrome and functional disorders. A close associative relationship was found between the level of galectin-3 and the clinical severity indexes of OA and the weak associative relationship between the level of galectin-3 and the age and duration of the diseaseДосліджено рівень галектину-3 в сироватці крові хворих на остеоартроз колінних суглобів. Встановлено, що у 75 % хворих на остеоартроз реєструються підвищенні рівні галектину-3 в крові порівняно зі здоровими особами. У хворих на остеоартроз рівень галектину-3 в крові асоціюється з віком, тяжкістю захворювання, больовим синдромом та порушенням функціональної здатност

Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial

Objective. To assess non-inferiority of s.c. to i.v. CT-P13 in RA. Methods. Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub- study, patients received CT-P13 s.c. via auto-injector (W46–54) then PFS (W56–64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6). Results. Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n ¼ 167) or CT-P13 i.v. (n ¼ 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n ¼ 162) and 1.94 (0.21) for CT-P13 i.v. [n ¼ 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. Conclusion. CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25–75 mL/min per 1·73 m² of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days) or end-stage kidney disease (eGFR <15 mL/min per 1·73 m² sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%) of 1325 patients in the atrasentan group and 105 (7·9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%) of 1325 patients in the atrasentan group and 34 (2·6%) of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%) patients in the atrasentan group and 52 (3·9%) in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding AbbVi

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

BACKGROUND Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Special peculiarities of clinical course of osteoarthrosis of knee joints depending on 6-hydroxymelatonin-sulfate urinary excretion profile

The study objective was to define the special features of the clinical course of knee joint osteoarthrosis depending on 6-sulfatoxymelatonin urinaryexcretion profile.Materials and methods.We surveyed 141 patients with radiological Stage II-III osteoarthrosis (OA) of the knee joints (18 female subjects). Diagnosis of OA was established on the basis of ACR criteria (1991) and EULAR (2010) recommendations. We determined the AO clinical indexes (Lequesne, WOMAC, KOOS), HAQ functional index, sleep quality and psycho-emotional state indicators. ELISA was used to assess 6-sulfatoxymelatonin urinary excretion profile.Results. It was established that 66% of patients with OA of knee joints had a reduced 6-sulfatoxymelatonin urinary excretion compared to this of practically healthy individuals. AO patients with low 6-SMT urinary excretion profiles had higher incidence of severe insomnia and depressive disorders. Reduction in 6-SMT excretion was associated with a moderate increase in pain syndrome and deterioration of physical functions by Lequesne, WOMAC, KOOS, and HAQ indexes.Conclusion.The reducedmelatonin production in ОА patients is a factor of more severe clinical course of the disease due to deterioration of the psycho-emotional state, the development of pain syndrome, and functional disorders

Clinical characteristics of ankylosing spondylitis patients depending on neuropathic pain

Introduction Neuropathic pain (NP) in ankylosing spondylitis (AS) is an important factor that complicates patients’ everyday activities and leads to a decrease of life quality. Detection and diagnosis of NP can be facilitated by the use of screening instruments, and the comparative assessment of the sensitivity of different scales is important for improving the diagnosis and personalizing the treatment of AS. The aim of the study was to analyze prevalence of NP in patients with AS and clinical features of AS patients depending on the presence of NP. Material and methods We examined 94 patients with NP and 48 patients without pain in AS using the following questionnaires: LANSS, DN4, StEP, BASFI, BASMI, BASDAI, HAQ, ASAS HI/EF and BAS-G. Results The prevalence of NP according to LANSS was 51.7% in women and 32.7% in men ( p = 0.048); according to DN4 – 58.6% and 32.7%, respectively ( p = 0.010). Disease activity and functional disability of the patients were higher in the group of patients with NP than in the group of patients without NP according to the BASDAI, BASFI, BASMI, HAQ, ASAS HI/EF and BAS-G. Significance of differences between groups was at the level of p < 0.01. Conclusions The prevalence of NP in AS is alarmingly high. Even with low scores on screening scales, patients showed signs of NP, which may indicate higher prevalence of NP. Neuropathic pain is more associated with the activity of the disease, greater loss of functional capacity and a decrease in indicators of the general state of health, which allows it to be considered as an aggravating factor regarding these manifestations