4 research outputs found
ΠΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΏΡΠΎΠ³Π½ΠΎΠ·Π° ΡΠΊΠΎΡΠΎΡΡΠΈ ΡΠΈΠ±ΡΠΎΠ·Π° ΠΏΠ΅ΡΠ΅Π½ΠΈ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ Ρ Ρ ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π³Π΅ΠΏΠ°ΡΠΈΡΠΎΠΌ Π‘ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΉ Π³Π΅Π½ΠΎΠΌΠ½ΡΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ²
Aim of study. To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, NOS3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC).Subjects and methods: 118 patients with CHC were divided into Β«fastΒ» and Β«slowΒ» (fibrosis rate progression β₯0,13 and 0,13 fibrosis units/yr; n =64 and n =54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10.Results. A allele (p =0,012) and genotype AA (p =0,024) of AGT G-6T gene, as well as T allele (p =0,013) and MT+TT genotypes (p =0,005) of AGT 235 M/T gene were significantly more common in Β«fast fibrosersΒ» than in Β«slow fibrosersΒ». Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p =0,02). Our analysis showed a protective effect of TT genotype of ITGA2 807 C/T on fibrosis progression rate (p =0,03). There was a trend (p 0,15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI -675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical model for prediction of liver fibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R =0,39, p =0,000).Conclusion: Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.Β ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠ΅. Π Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ Π±ΠΎΠ»ΡΡΠΎΠ΅ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ ΡΠ΄Π΅Π»ΡΠ΅ΡΡΡ ΠΏΠΎΠΈΡΠΊΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ°ΠΊΡΠΎΡΠΎΠ², ΠΎΠ±ΡΡΡΠ½ΡΡΡΠΈΡ
ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π³Π΅ΠΏΠ°ΡΠΈΡΠ° Π‘ (Π₯ΠΠ‘).Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΠΎΡΠ΅Π½ΠΈΡΡ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΡΡ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ Π½ΠΎΡΠΈΡΠ΅Π»ΡΡΡΠ²Π° ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΉ Π°Π»Π»Π΅Π»ΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½ΠΎΠ² IL 1b, IL 6, IL 10, TNF Ξ±, HFE, TGF b, ATR1, NOS3, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI Π½Π° ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΈΠ±ΡΠΎΠ·Π° ΠΏΠ΅ΡΠ΅Π½ΠΈ ΠΏΡΠΈ Π₯ΠΠ‘.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ: 118 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π₯ΠΠ‘ ΡΠ°Π·Π΄Π΅Π»Π΅Π½Ρ Π½Π° Π³ΡΡΠΏΠΏΡ Ρ Π±ΡΡΡΡΡΠΌ ΠΈ ΠΌΠ΅Π΄Π»Π΅Π½Π½ΡΠΌ (ΡΠΊΠΎΡΠΎΡΡΡ ΡΠΈΠ±ΡΠΎΠ·Π° β₯0,13 ΠΈ 0,13 Π΅Π΄. ΡΠΈΠ±ΡΠΎΠ·Π°/Π³ΠΎΠ΄; n =64 ΠΈ n =54, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ) ΡΠΈΠ±ΡΠΎΠ·ΠΎΠΌ. ΠΡΠΏΠΎΠ»Π½Π΅Π½ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ°. Π‘ΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΡΡ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠ°ΠΊΠ΅ΡΠΎΠ² ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌ Statistica 10.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π£ Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ Π±ΡΡΡΡΡΠΌ ΡΠΈΠ±ΡΠΎΠ·ΠΎΠΌ Π² ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ Π³ΡΡΠΏΠΏΠΎΠΉ Ρ ΠΌΠ΅Π΄Π»Π΅Π½Π½ΡΠΌ ΡΠ°ΡΠ΅ Π²ΡΡΡΠ΅ΡΠ°Π»ΠΈΡΡ Π°Π»Π»Π΅Π»Ρ Π (Ρ =0,012) ΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΠΉ Π³Π΅Π½ΠΎΡΠΈΠΏ ΠΠ (Ρ =0,024) Π³Π΅Π½Π° AGT G-6T, ΡΠ°ΠΊΠΆΠ΅ Π² Π΄Π°Π½Π½ΠΎΠΉ Π³ΡΡΠΏΠΏΠ΅ ΡΠ°ΡΠ΅ Π²ΡΡΠ²Π»ΡΠ»ΠΈ Π°Π»Π»Π΅Π»Ρ Π’ (Ρ =0,013) ΠΈ Π³Π΅Π½ΠΎΡΠΈΠΏ ΠΠ’+Π’Π’ Π³Π΅Π½Π° AGT 235 M/T (Ρ =0,005). ΠΠΎΠ»ΡΠ½ΡΠ΅ Ρ Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠΌ Π’Π’ Π³Π΅Π½Π° CYBA 242 C/T ΠΈΠΌΠ΅Π»ΠΈ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΡΡ ΡΠΊΠΎΡΠΎΡΡΡ ΡΠΈΠ±ΡΠΎΠ·Π° ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π±ΠΎΠ»ΡΠ½ΡΠΌΠΈ Ρ Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠΌ Π‘Π‘+Π‘Π’ (Ρ =0,02). Π Ρ
ΠΎΠ΄Π΅ Π°Π½Π°Π»ΠΈΠ·Π° Π²ΡΡΠ²Π»Π΅Π½ΠΎ ΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π³ΠΎΠΌΠΎΠ·ΠΈΠ³ΠΎΡΡ Π’Π’ Π³Π΅Π½Π° ITGA2 807 C/T Π½Π° ΡΠ΅ΠΌΠΏΡ ΡΠΈΠ±ΡΠΎΠ·Π° (Ρ =0,03). ΠΠ°Π±Π»ΡΠ΄Π°Π»ΠΈΡΡ ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΠΈ ΠΊ ΡΠ°Π·Π»ΠΈΡΠΈΡ ΠΏΠΎ Π²ΡΡΡΠ΅ΡΠ°Π΅ΠΌΠΎΡΡΠΈ Π°Π»Π»Π΅Π»Π΅ΠΉ ΠΈ Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠ² ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² TGFb +915 G/Π‘, FXIII 103 G/T, PAI -675 5G/4G ΠΌΠ΅ΠΆΠ΄Ρ Π΄Π²ΡΠΌΡ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ. ΠΠ»Ρ ΠΎΡΡΠ°Π»ΡΠ½ΡΡ
Π³Π΅Π½ΠΎΠ² Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΡΡ
ΠΎΡΠ»ΠΈΡΠΈΠΉ Π½Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ. Π Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΌ ΠΏΠΎΡΡΡΠΎΠ΅Π½Π° ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΌΠΎΠ΄Π΅Π»Ρ, ΡΡΠΈΡΡΠ²Π°ΡΡΠ°Ρ ΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ΅ ΠΈ ΠΏΡΠΎΡΠΈΠ±ΡΠΎΠ³Π΅Π½Π½ΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ², Π² ΡΠ°ΠΊΠΆΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π³Π΅Π½ΠΎΡΠΈΠΏΠ° Π²ΠΈΡΡΡΠ°. ΠΡΡΠ²Π»Π΅Π½Π° ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΡ ΠΌΠ΅ΠΆΠ΄Ρ ΡΡΠΌΠΌΠΎΠΉ Π±Π°Π»Π»ΠΎΠ² Π² ΡΡΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΈ ΡΠ΅ΠΌΠΏΠΎΠΌ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΈΠ±ΡΠΎΠ·Π° Π² ΠΏΠ΅ΡΠ΅Π½ΠΈ (R =0,39, p =0,000).ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅: ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½Π°Ρ ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°ΡΡ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π±ΠΎΠ»Π΅Π·Π½ΠΈ
Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4.5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial
Background: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4.5 h after symptom onset. Methods: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4.5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0.9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0-1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. Findings: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89-89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1.47, 95% CI 0.93 to 2.32; p=0.10). The difference in the rate of favourable outcome at day 90 was 9.5% (95% CI -1.7 to 20.7) and the lower limit did not cross the margin of non-inferiority (p(non-inferiority) <0.0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0.087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0.32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0.044). Interpretation Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4.5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. Copyright (C) Elsevier Ltd. All rights reserved
Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4Β·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial
Background: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4Β·5 h after symptom onset. Methods: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4Β·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0Β·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0β1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0β1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. Findings: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89β89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1Β·47, 95% CI 0Β·93 to 2Β·32; p=0Β·10). The difference in the rate of favourable outcome at day 90 was 9Β·5% (95% CI β1Β·7 to 20Β·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0Β·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0Β·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0Β·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0Β·044). Interpretation: Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4Β·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. Funding: The Russian Academy of Sciences. Β© 2021 Elsevier Lt