Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial
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01.12.2021 |
Alexeeva E.
Horneff G.
Dvoryakovskaya T.
Denisova R.
Nikishina I.
Zholobova E.
Malievskiy V.
Santalova G.
Stadler E.
Balykova L.
Spivakovskiy Y.
Kriulin I.
Alshevskaya A.
Moskalev A.
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Pediatric Rheumatology |
10.1186/s12969-020-00488-9 |
0 |
Ссылка
© 2021, The Author(s). Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
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Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial
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01.12.2021 |
Alexeeva E.
Horneff G.
Dvoryakovskaya T.
Denisova R.
Nikishina I.
Zholobova E.
Malievskiy V.
Santalova G.
Stadler E.
Balykova L.
Spivakovskiy Y.
Kriulin I.
Alshevskaya A.
Moskalev A.
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Pediatric Rheumatology |
10.1186/s12969-020-00488-9 |
0 |
Ссылка
© 2021, The Author(s). Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
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Multiple sleep latency test and polysomnography in patients with central disorders of hypersomnolence
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01.03.2021 |
Dietmann A.
Gallino C.
Wenz E.
Mathis J.
Bassetti C.L.A.
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Sleep Medicine |
10.1016/j.sleep.2020.12.037 |
0 |
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© 2021 The Authors A multiple sleep latency test (MSLT) with occurrence of sleep onset REM periods (SOREMP) is considered one of the central diagnostic criteria for narcolepsy according to the International Classification of Sleep Disorders, but its sensitivity and specificity have been questioned. This study aims to describe MSLT and polysomnography (PSG) findings, including frequency and distribution of SOREMP during the day, in a large cohort of patients with central disorders of hypersomnolence (CDH). We retrospectively analyzed electrophysiological data from MSLT and PSG in 370 consecutive patients with narcolepsy type 1 (NT1, n = 97), type 2 (NT2, n = 31), idiopathic hypersomnia (IH, n = 48), nonorganic hypersomnia (NOH, n = 116) and insufficient sleep syndrome (ISS, n = 78). NT1 and NT2 patients had a significantly shorter mean Sleep Latency (mSL) and REM-Latency (REML) in MSLT and PSG. SOREMP occurred more frequently in narcoleptic vs. non-narcoleptic patients in MSLT and PSG. Occurrence of 3 or more SOREMP in MSLT and a SOREMP in PSG had a very high specificity and positive predictive value (98%/96% and 100% respectively), however relatively low sensitivity (65% and 45% respectively). NT1 more than NT2 patients have shorter mSL and more frequent SOREMP in MSLT and shorter SL as well as REML during nocturnal PSG. Increasing numbers of SOREMP in MSLT and especially SOREMP during PSG increase specificity on the expense of sensitivity in diagnosing narcolepsy. Therefore, frequency of SOREMP in MSLT naps and PSG can help to discriminate but not clearly separate narcoleptic from non-narcoleptic patients.
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Multiple sleep latency test and polysomnography in patients with central disorders of hypersomnolence
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01.03.2021 |
Dietmann A.
Gallino C.
Wenz E.
Mathis J.
Bassetti C.L.A.
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Sleep Medicine |
10.1016/j.sleep.2020.12.037 |
0 |
Ссылка
© 2021 The Authors A multiple sleep latency test (MSLT) with occurrence of sleep onset REM periods (SOREMP) is considered one of the central diagnostic criteria for narcolepsy according to the International Classification of Sleep Disorders, but its sensitivity and specificity have been questioned. This study aims to describe MSLT and polysomnography (PSG) findings, including frequency and distribution of SOREMP during the day, in a large cohort of patients with central disorders of hypersomnolence (CDH). We retrospectively analyzed electrophysiological data from MSLT and PSG in 370 consecutive patients with narcolepsy type 1 (NT1, n = 97), type 2 (NT2, n = 31), idiopathic hypersomnia (IH, n = 48), nonorganic hypersomnia (NOH, n = 116) and insufficient sleep syndrome (ISS, n = 78). NT1 and NT2 patients had a significantly shorter mean Sleep Latency (mSL) and REM-Latency (REML) in MSLT and PSG. SOREMP occurred more frequently in narcoleptic vs. non-narcoleptic patients in MSLT and PSG. Occurrence of 3 or more SOREMP in MSLT and a SOREMP in PSG had a very high specificity and positive predictive value (98%/96% and 100% respectively), however relatively low sensitivity (65% and 45% respectively). NT1 more than NT2 patients have shorter mSL and more frequent SOREMP in MSLT and shorter SL as well as REML during nocturnal PSG. Increasing numbers of SOREMP in MSLT and especially SOREMP during PSG increase specificity on the expense of sensitivity in diagnosing narcolepsy. Therefore, frequency of SOREMP in MSLT naps and PSG can help to discriminate but not clearly separate narcoleptic from non-narcoleptic patients.
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Multiple sleep latency test and polysomnography in patients with central disorders of hypersomnolence
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01.03.2021 |
Dietmann A.
Gallino C.
Wenz E.
Mathis J.
Bassetti C.L.A.
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Sleep Medicine |
10.1016/j.sleep.2020.12.037 |
0 |
Ссылка
© 2021 The Authors A multiple sleep latency test (MSLT) with occurrence of sleep onset REM periods (SOREMP) is considered one of the central diagnostic criteria for narcolepsy according to the International Classification of Sleep Disorders, but its sensitivity and specificity have been questioned. This study aims to describe MSLT and polysomnography (PSG) findings, including frequency and distribution of SOREMP during the day, in a large cohort of patients with central disorders of hypersomnolence (CDH). We retrospectively analyzed electrophysiological data from MSLT and PSG in 370 consecutive patients with narcolepsy type 1 (NT1, n = 97), type 2 (NT2, n = 31), idiopathic hypersomnia (IH, n = 48), nonorganic hypersomnia (NOH, n = 116) and insufficient sleep syndrome (ISS, n = 78). NT1 and NT2 patients had a significantly shorter mean Sleep Latency (mSL) and REM-Latency (REML) in MSLT and PSG. SOREMP occurred more frequently in narcoleptic vs. non-narcoleptic patients in MSLT and PSG. Occurrence of 3 or more SOREMP in MSLT and a SOREMP in PSG had a very high specificity and positive predictive value (98%/96% and 100% respectively), however relatively low sensitivity (65% and 45% respectively). NT1 more than NT2 patients have shorter mSL and more frequent SOREMP in MSLT and shorter SL as well as REML during nocturnal PSG. Increasing numbers of SOREMP in MSLT and especially SOREMP during PSG increase specificity on the expense of sensitivity in diagnosing narcolepsy. Therefore, frequency of SOREMP in MSLT naps and PSG can help to discriminate but not clearly separate narcoleptic from non-narcoleptic patients.
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Dynamics of concomitant therapy in children with juvenile idiopathic arthritis treated with etanercept and methotrexate
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01.10.2019 |
Alexeeva E.
Dvoryakovskaya T.
Denisova R.
Sleptsova T.
Isaeva K.
Chomahidze A.
Fetisova A.
Mamutova A.
Alshevskaya A.
Gladkikh V.
Moskalev A.
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Pediatrics and Neonatology |
10.1016/j.pedneo.2019.02.003 |
2 |
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© 2019 Background: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient's condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA. Methods: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years). Results: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy. Conclusion: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high.
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Comparative analysis of the etanercept efficacy in children with juvenile idiopathic arthritis under the age of 4 years and children of older age groups using the propensity score matching method
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03.09.2019 |
Alexeeva E.
Dvoryakovskaya T.
Denisova R.
Sleptsova T.
Isaeva K.
Chomahidze A.
Fetisova A.
Mamutova A.
Alshevskaya A.
Gladkikh V.
Moskalev A.
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Modern Rheumatology |
10.1080/14397595.2018.1516329 |
1 |
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© 2018, © 2018 Japan College of Rheumatology. Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups. Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group). Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3–6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3–9) months (p =.028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p =.045). Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.
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Neutropenia during tocilizumab treatment is not associated with infection risk in systemic or polyarticular-course juvenile idiopathic arthritis
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01.09.2019 |
Pardeo M.
Wang J.
Ruperto N.
Alexeeva E.
Chasnyk V.
Schneider R.
Horneff G.
Huppertz H.
Minden K.
Onel K.
Zemel L.
Martin A.
Koné-Paut I.
Siamopoulou-Mavridou A.
Silva C.
Porter-Brown B.
Bharucha K.
Brunner H.
De Benedetti F.
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Journal of Rheumatology |
10.3899/jrheum.180795 |
0 |
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© 2019 The Journal of Rheumatology. All rights reserved. Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.
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Growth during tocilizumab therapy for polyarticular-course juvenile idiopathic arthritis: 2-year data from a phase III clinical trial
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01.08.2018 |
Bharucha K.
Brunner H.
Penadés I.
Nikishina I.
Rubio-Pérez N.
Oliveira S.
Kobusinska K.
Schmeling H.
Sztajnbok F.
Weller-Heinemann F.
Zholobova E.
Zulian F.
Allen R.
Chaitow J.
Frane J.
Wells C.
Ruperto N.
De Benedetti F.
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Journal of Rheumatology |
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1 |
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Copyright © 2018. All rights reserved. Objective: Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial. Methods: Patients with pcJIA lasting at least 6 months and inadequate response to methotrexate received open-label TCZ intravenously every 4 weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8 mg/kg if they weighed ≥ 30 kg) for 16 weeks. Patients with JIA American College of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo for 24 weeks, with an open-label extension through Week 104. Mean ± SD height velocity (cm/yr) and World Health Organization (WHO) height SD score (SDS) were measured in patients receiving ≥ 1 dose of TCZ who did not receive growth hormone and in patients whose baseline Tanner stage was ≤ 3. Results: The study included 187 of 188 patients (99.5%) with mean WHO height SDS -0.5 ± 1.2, which was unrelated to age or disease duration (Spearman rank correlations r = 0.08 and r = -0.12, respectively). There were 123 patients at Tanner stage ≤ 3 at baseline, among whom 103 completed the study with 2 years of height SDS data. Mean height SDS increased from baseline to year 2 (+0.40, p < 0.0001). In 74 of 103 patients (72%), height SDS was greater than at baseline, and mean height velocity was 6.7 ± 2.0 cm/year. Conclusion. Among patients with pcJIA at Tanner stage ≤ 3 at baseline, 72% (74/103) had increased height SDS at the end of the study.
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Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial
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01.07.2018 |
Opoka-Winiarska V.
Żuber Z.
Alexeeva E.
Chasnyk V.
Nikishina I.
Dębowska G.
Smolewska E.
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Clinical Rheumatology |
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2 |
Ссылка
© 2018, The Author(s). Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783.
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Selection and switching of genetically engineered biological agents in treatment of juvenile arthritis
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01.05.2018 |
Zholobova E.
Ignatova A.
Seylanova N.
Golubeva A.
Shpitonkova O.
Afonina E.
Nikolaeva M.
Chebysheva S.
Meleshkina A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Therapy with genetically engineered biological preparations (GEBP) significantly improved the prognosis and quality of life of patients with juvenile idiopathic arthritis (JIA). However, primary or secondary in efficiency, the development of undesirable phenomena require switching to another GEBP. Objective of the research – to determine optimal GEBP preparations when selecting and switching therapy based on the analysis of prescribed GEBP in real practice, depending on the clinical version of the JIA and the presence of uveitis. Materials and methods: the study included 322 patients with JIA on GEBP therapy, observed in the Pediatric Rheumatology Department of Children's Clinical Hospital of the I.M. Sechenov First Moscow State Medical University from Jan. 1, 2015 to Dec. 31, 2017. Retrospective, continuous observational clinical study. Of 322 patients, 70 (21,74%) had systemic JIA, 155 patients (48,14%) had polyarterial seronegative for rheumatoid factor (RF–) variant of JIA, 9 patients (2,8%) – polyarticular seropositive for rheumatoid factor RF+) variant of JIA, 55 patients (17,08%) – oligoarticular (persistent and spreading) variant of JIA, 26 patients (8,07%) – enthesitis (juvenile spondylitis), 7 patients (2,17%) – psoriatic variant of JIA. Results: as the first biological preparation were prescribed: etanercept to 177 (54,97%) patients; adalimumab to 51 (15,84%); tocilizumab to 44 (13,66%); abatacept to 39 (12,11%); infliximab to 11 (3,42%) patients. Transition to the second line of biological therapy was performed in 51 patients (in 15,8% of cases), on the third line of therapy in 13 patients (in 4,04% of cases), on the fourth line in 3 patients (in 0,93% of cases). As the second-line GEBP adelimumab was prescribed in 22 cases (43,14%), tocilizumab in 13 (25,49%), etanercept in 11 (21,57%), abatacept in 5 (9,8%). GEBP inefficiency was the reason for switching to the second line in 32 cases (9,9%). Of these, secondary inefficiency in 22 cases (6,8%); primary inefficiency – in 4 (1,3%), low efficiency – in 6 (1,9%), development/exacerbation of uveitis – in 7 patients (2,2%), in 6 cases (1,9%) due to insufficient compliance, drug shortage in the community, etc. Adverse effects caused switching in 5 patients (1,6%), incl. in 4 children – infusion reactions, in one – tuberculosis. Analysis of GEBP choice depending on the disease form and the presence of uveitis, was performed in 3 groups. Group 1 (n=70) consisted of patients with systemic JIA. Group 2 (n=53) included patients with articular form of JIA and concomitant uveitis. Group 3 (n=199) included patients with articular form of JIA without concomitant uveitis. Patients with systemic JIA as the first-line GEBP tocilizumab was prescribed significantly more often – to 38 patients out of 70 (54,29±5,96%) than etanercept – to 19 patients (27,14±10,19%) (t=2, 3, p<0,05), and other drugs in total (infliximab, abatacept, adalimumab) – to 13 (18,57±10,88%) (t=2,9, p<0,05). Switching to GEBP second line in this group was performed in 20 patients (28,57%). Tocilizumab was the final choice drug (after 3 years of follow-up) at the time of samples collection in 50 patients (71,43%) with systemic JIA. In patients with articular forms of JIA and concomitant uveitis as the first-line GEBP, adalimumab was prescribed significantly more often – in 34 of 53 cases (64,15±8,23%) than other drugs (abatacept, etanercept, infliximab) in total – 19 of 53 cases (35,85±11,01%) (t=2,06, p<0,05). Adalimumab was the drug final choice at the time of sample collection for 43 (81,13%) patients with JIA and uveitis. Most patients with articular form without uveitis received etanercept as first-line GEBP, 150 of 199 (75,38±3,54%), and etanercept prescription frequency was significantly higher than that of other drugs (abatacept, adalimumab, tocilizumab, infliximab) in total – 49 of 199 (24,62±6,19%) (t=7,1, p<0,01). In this group, the switching frequency was the smallest and amounted only 8,54%. The number of patients who received etanercept at the end of the study actually remained unchanged – 148 patients (74,37%).
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Vitamin D status in children with rheumatic diseases
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01.01.2018 |
Podchernyaeva N.
Geppe N.
Ivina A.
Shpitonkova O.
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Voprosy Prakticheskoi Pediatrii |
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1 |
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© 2018, Dynasty Publishing House. All rights reserved. The objective. To determine vitamin D status in children with rheumatic disease who live on the territory of Russia. Patients and methods. A pilot study was conducted that included 52 children (35 girls and 17 boys) aged 5 to 17 years (11.88 ± 0.48 years), among them 29 children with systemic connective tissue disorders (SCTD) and 23 children with juvenile idiopathic arthritis (JIA). All patients underwent complex clinical-laboratory and instrumental examination in order to confirm the diagnosis and assess the patients’ health. Vitamin D status was assessed by 25(ОН)D serum levels using the method of chemiluminescence immunoassay. Results. Sufficient levels of 25(ОН)D (>30 ng/l) were found only in 5 (9.5%) children, vitamin D insufficiency (25(ОН)D 21–30 ng/l) was observed in 6 (11.5%) children, deficiency (25(ОН) <20 ng/l) in 41 (79.0%) children, among them in 7 (13.4%) it was severe (25(OH)D <10 ng/l), in spite of a long-term intake of low-doses of cholecalciferol (100–400 U/day) by 40 (76.9%) patients. Average levels of 25(ОН)D in patients with SCTD were significantly higher than in patients with JIA (20.86 ± 2.15 ng/l vs. 14.98 ± 0.91 ng/l, p = 0.0151), deficiency was more rarely found in these patients (69.0% vs. 91.3%), which was to a certain degree conditioned by more intensive vitamin D therapy. Conclusion. Insufficiency/deficiency of vitamin D is noted in an overwhelming majority of children with RD. Standard therapy with low doses of cholecalciferon offered to patients with RD is not sufficient for obtaining optimal 25(ОН)D levels and needs correction.
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New tactics for the treatment of pulmonary hypertension: Switching to a more effective therapy
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01.01.2018 |
Tsareva N.
Avdeev S.
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Kardiologiya |
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0 |
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© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. The article deals with the modern tactics of pulmonary hypertension therapy, used in case of unsatisfactory clinical response to previous therapy. All classes of pathogenetic therapy of pulmonary hypertension are presented, as well as modern views on the risk stratification of annual mortality of patients. Switching to a more effective drug both within one group of pathogenetic PAHtherapy, and to drugs of other classes is discussed. The latest classification of pulmonary hypertension (Nice, 2018) is presented.
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Experience of vaccination of a patient with systemic juvenile idiopathic arthritis (sJIA) with a 13-valent pneumococcal conjugate vaccine, prior to the appointment of therapy with tocilizumab, an anti-IL-6-receptor monoclonal antibody
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01.01.2018 |
Vankova D.
Alekseeva E.
Soloshenko M.
Dvoriakovskaia T.
Isaeva K.
Denisova R.
Mamutova A.
Rudnitskaya M.
Mayansky N.
Tkachenko N.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Infections are the main cause of death for patients with autoimmune rheumatic diseases. In adult patients with rheumatoid arthritis (RA), mortality caused by respiratory infections is 2-5 times higher than in the population. One of the frequent infectious complications in the course of treatment with tocilizumab, the first-choice drug for treating systemic juvenile idiopathic arthritis (sJIA), is pneumonia characterized by a poor clinical picture, normal values of laboratory indices of the disease activity (ESR, C-reactive protein) with pronounced changes in the lungs revealed by computed tomography. In case of acute respiratory infection in children with systemic JIA, immunosuppressants and genetically engineered biological preparations (GEBP) are discontinued. This often leads to an exacerbation of the underlying disease and the progression of a pathological process. At present, vaccination against pneumococcal infection in Russia is not included in the standard for managing patients with rheumatic diseases. Studies of the safety and efficacy of vaccination with 13-valent pneumococcal conjugate vaccine (PCV) in patients with sJIA receiving genetically engineered biological preparations were not conducted. Clinical Case Description. The article shares the experience of vaccination of a girl aged 9 years with a 13-valent PCV that was conducted in the course of a scientific investigation, which studied the efficacy and safety of vaccination of children with systemic JIA prior to prescription of GEBP tocilizumab. Vaccination did not cause a deterioration in the course of the main disease (1 month), led to a reduction in the incidence of acute respiratory infections (from 4 to 1 time within 6 months before and after vaccination), and discontinuation of antibacterial drugs within 6 months after vaccination. Conclusion. The safety of a 13-valent PCV in a child with sJIA and a decrease of the incidence of respiratory diseases after vaccination, their complications, and the use of antibacterial drugs have been shown.
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Switching to a second TNF-α inhibitor in a patient with severe juvenile polyarthritis: A clinical case
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01.01.2018 |
Denisova R.
Alexeeva E.
Dvoryakovskaya T.
Soloshenko M.
Mamutova A.
Isayeva K.
Fetisova A.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Insufficient efficacy or intolerance of the first TNF-α inhibitor in patients with juvenile idiopathic arthritis (JIA) is an indication for the appointment of a second inhibitor. Golimumab is a new TNF-α inhibitor registered for treating JIA under pediatric indications. Clinical Case Description. At an early age, the patient had an onset of polyarticular JIA. Due to the aggressive and rapidly progressive course, failure of therapy with nonsteroidal anti-inflammatory drugs, methotrexate and glucocorticosteroids for intra-articular administration, infliximab was prescribed to the patient, with a positive effect. Subsequently, the patient developed a secondary resistance to infliximab, inflammatory changes in the joints relapsed; thus, a second TNF-α inhibitor (golimumab) was prescribed. In the course of therapy, pain and signs of arthritis in the patient were reversed, and the range of motion in the affected joints increased. After one year of therapy, JIA remission was ascertained. At the same time, the child was not administered oral glucocorticosteroids. The duration of remission of the joint syndrome was 5 years. Adverse events were not serious and did not constitute a basis for drug discontinuation. Conclusion. Switching to a second TNF-α inhibitor (golimumab) was effective in a patient with a secondary resistance to the first TNF-α inhibitor.
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Effect of monotherapy with methotrexate, etanercept and their combination on the quality of life in children with early and late juvenile idiopathic arthritis: A prospective study
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01.01.2018 |
Alexeeva E.
Fetisova A.
Dvoryakovskaya T.
Chernikov V.
Vinyarskaya I.
Denisova R.
Soloshenko M.
Isaeva K.
Mamutova A.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Abstarct:-Background. An important goal of treating patients with juvenile idiopathic arthritis (JIA) is to achieve the best quality of life associated with health. Objective. Our aim was to assess the impact of methotrexate plus etanercept therapy on the quality of life of patients with early and late JIA. Methods. The prospective study included patients with early and late JIA without systemic manifestations. The patients' quality of life was assessed with the help of questionnaires for children and parents: the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale, the Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module, and the Health Utilities Index Mark 3 (HUI3). The quality of life was assessed prior to the therapy and after one, six, and 12 months of treatment. Results. 150 children with JIA aged 5.1 (2.0; 17.7) years; 50 children aged 4.0 (2.3-11.4) years in the group of etanercept monotherapy, 50 children aged 5.0 (3.2-9.0) years in the group of methotrexate monotherapy, and 50 children aged 9.9 (6.4-13.0) years in the group of methotrexate plus etanercept combination therapy. All groups showed low scores on all questionnaires before treatment, compared to healthy children. In the course of therapy, there was a tendency for score increase to almost 1.0 according to the HUI3 questionnaire in all groups. After one year of etanercept therapy, the parameters of the quality of life of children with early JIA did not differ from healthy children; the score increased from 56 to 90 p = 0.942 according to the physical functioning scale and from 60 to 85 p = 0.889 according to the emotional functioning scale. In the 2nd group, there was a tendency for score increase, but a statistically significant difference was found across all scales of the questionnaire. After 12 months of etanercept plus methotrexate combination therapy in patients with late JIA, the questionnaire analysis showed that the responses of healthy children and children with JIA differed with probability p = 0.001 for the physical functioning scale, p = 0.001 for the social functioning scale, p = 0.001 for role functioning, and p = 0.001 for the total score. The score increase from 60 to 85 p = 0.789 was noted for emotional functioning scales. Conclusion. The use of questionnaires to assess the quality of life in children with severe chronic diseases can significantly improve the efficacy of treatment and ensure its control.
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Acute exacerbation of idiopathic pulmonary fibrosis
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01.01.2018 |
Avdeev S.
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Pulmonologiya |
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© 2018 National Research University Higher School of Economics. All rights reserved. Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is defined as an acute clinically significant respiratory deterioration characterized by evidence of new, widespread alveolar abnormalities, such as diffuse bilateral ground-glass opacification and/or consolidation, and the absence of other obvious clinical causes like fluid overload, left heart failure, or pulmonary embolism, etc. AE-IPF is subcategorized as “triggered” (where specific causes are identified, for example, infections, surgery procedures, drug toxicity, etc.) or “idiopathic” (where no specific causes are identified). In randomized trials, the annual incidence of AE-IPF is about 8%, in retrospective studies it reaches 19%. Severe forms of IPF are an important risk factor for the development of AE-IPF. In-hospital mortality from AE-IPF is more than 50%, and the average survival of patients with AE-IPF is 1-4 months. Currently, there remain no proven, effective therapies for AE-IPF. In real clinical practice patients with AE-IPF still receive high doses of systemic corticosteroids and antibiotics. Antifibrotic therapy can reduce the risk of exacerbations; it has been shown that therapy with nintedanib leads to a reduction in the number of confirmed/suspected AE-IPF by 68%. It is necessary to further study the potential methods of prevention and therapy of AE-IPF in future clinical trials.
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Apoptosis in seminiferous tubules of human in normal and in idiopathic infertility
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01.01.2018 |
Demyashkin G.
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Tsitologiya |
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© 2018 Sankt Peterburg. All rights reserved. The purpose of this study was to assess the level of apoptosis in cells of human seminiferous tubules in normal and pathological spermatogenesis by revealing the proportion of immunostaining cells for caspase-9 and -3 and by comparing the expression of pro-apoptotic (BAK and BAX) and anti-apoptotic genes (BCL2 and BCLW). A retrospective study involved men (n = 42) who complained of childlessness in marriage for 2 years with a diagnosis of idiopathic infertility, established after physical, genetic, biochemical (hormones) and cytological (spermogram) analyzis. The biopsies of the testes as well as the autopsy material of men 22—35 (n = 10), 64—75 (n = 10) and 75—90 (n = 10) years were studied using the immunohistochemical method (caspase-9 and -3) and PCR-RT. The marking level for caspase-9 in spermatogonies with normal spermatogenesis is approximately at the same level (the proportion of stained spermatogonies is 39.5 0.33 % in young men, 35.6 0.44 % in the elderly, and 32.2 0.28 % in man of senile age), and increases when the maturation is blocked and in the case of focal variant of Sertoli-cell-only syndrome (64.3 0.39 and 72.0 0.41 %, respectively). When using antibodies to caspase-3, the percentage of immunopositive spermatogonia in normal spermatogenesis was 60.1 0.44 % in young men, 78.2 1.2 % in the elderly, and 87.3 0.9 % in men of senille age, and with idiopathic infertility, a sharp increase in the proportion of labeled spermatogonia was observed (an average of 91.4 1.1 %). In the case of hypospermatogenesis and the blocking of maturation, a significant increase in the relative level of expression of the proapoptotic genes of the internal pathway of apoptosis of BAX and BAK was observed against the background of a decrease in the expression of the anti-apoptotic genes BCL2 and BCLW, compared to men of the same age but with normal spermatogenesis. Based on the results, we can conclude that in the elderly’s testes the receptor-mediated pathway of apoptosis predominates over the mitochondrial (internal) pathway. In the idiopathic form of male infertility the internal pathway of apoptosis is dominant. An increase in the activity of apoptosis markers can be associated with impaired maturation of the germ cells in the meiosis block and with the depletion of the germ cell pool in Sertoli-cell-only syndrome.
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Idiopathic lobular panniculitis in rheumatology practice: The authors’ own data
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01.01.2018 |
Egorova O.
Belov B.
Glukhova S.
Radenska-Lopovok S.
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Nauchno-Prakticheskaya Revmatologiya |
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© 2018 Ima-Press Publishing House. All rights reserved. Idiopathic lobular panniculitis (ILP) (synonym: Weber-Christian panniculitis) is the least studied disease in the group of systemic connective tissue lesions and characterized by systemic damage to subcutaneous adipose tissue (SAT). There is no unified concept of the etiology and pathogenesis of ILP now. The literature contains almost no data on the diagnostic value of laboratory studies and therapeutic approaches, which served as the basis for this investigation. Objective: to investigate the relationship between the clinical presentation of ILP and immune inflammatory parameters in patients with this disease. Subjects and methods. Examinations were made in 67 patients (9 men and 58 women) aged 20 to 76 years with a verified diagnosis of ILP (median duration, 78.91 [48; 540] months), who were followed up at the V.A. Nasonova Research Institute of Rheumatology for the period 2007 to 2017. The determination of α1-antitrypsin titer, liver fractions, amylase, lipase, trypsin, ferritin, creatine phosphokinase, leptin, and tumor necrosis factor-α (TNFα), chest computed tomography, and induration morphological examination were done in addition to physical examination. Results and discussion. The disease was found in all age groups, but it accounted for more than half (57%) of cases at the most able-bodied age (45–60 years). Analysis of the clinical manifestations of ILP could identify its four types: nodular (n=30), plaque (n=10), infiltrative (n= 5), and mesenteric (n=12), which were characterized by typical clinical features. The observed group showed a significant increase in erythrocyte sedimentation rate (ESR) (p=0.01) and C-reactive protein (CRP) level (p < 0.0001). ESR correlated with tenderness on the visual analogue scale (VAS) (p<0.05; r=0.29), induration area (p<0.05; r=0.50), and rises in body temperature (p<0.05; r=0.68) and CRP level (p<0.05; r=0.68). The concentration of CRP correlated with tenderness on visual analog scale (p<0.05; r=0.46), induration area (p<0.05; r=0.61), node stage (p<0.05; r=0.41), and TNF-α concentrations (p<0.05; r=0.32). The latter showed a direct correlation with node stage (p<0.05; r=0.41) and leptin levels (p<0.05; r=0.28) and an inverse correlation with the number of nodes (p<0.05; r=-0.24). Leptin levels were increased in 35 (52.23%) patients and displayed a direct correlation with body mass index (p<0.05; r=0.46), induration area (p<0.05; r=0.31), CRP level (p<0.05; r=0.36) and an inverse correlation with the number of nodes (p≤0.05; r=-0.33). Morphological examination of skin and SAT biopsy specimens was performed in 65 (97.01%) patients. Pre- and retroperitoneal adipose tissues were biopsied in three of five patients without skin and SAT lesions; this was not done in the remaining patients because of access difficulties. ILP was verified in all cases. Therapy was performed using the essential drugs adopted in rheumatology practice. Their therapeutic effects were noted in 62.68% of cases; inefficiency and health deterioration were detected in 12 (17.91%) patients, which necessitated an increase in the dose of disease-modifying antirheumatic drugs. Seven patients were given the following biological agents: abatacept (n=2), adalimum-ab (n = 3), etanercept (n=1), and rituximab (n=1). Conclusion. There is an obvious need to expand knowledge about this pathology amongst physicians and to conduct further investigation in order to timely diagnose and search for the most effective treatment options for ILP.
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Genetic determinants of the development and course of membranous nephropathy
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01.01.2018 |
Kamyshova E.
Bobkova I.
Gorelova I.
Êàkhsurueva P.
Filatova E.
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Terapevticheskii Arkhiv |
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© 2018 Media Sphera Publishing Group. All rights reserved. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.
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