Влияние Эреспала на клиническое течение и показатели воспаления у больных хронической обструктивной болезнью легких

We studied effects of Eurespal (fenspirid) on clinical course and inflammation in COPD patients. The trial included 2 stages: 3-week therapy of exacerbation and 3-month outpatient treatment in stable condition. The drug was given twice a day, 160 mg dally. We assessed scoring of main clinical signs, lung function parameters, bronchoscopic findings, laboratory markers of inflammation, antioxidant status, and quality of life, performed cytological and cytochemical investigation of induced sputum (IS). During the exacerbation Eurespal had early and distinct cough-inhibiting and mucolytic effects, reduced bronchial obstruction, bronchial inflammation severity, decreased C-reactive protein level, IS cytosis, and neutrophil percentage (p < 0.01), increased IS concentration of lyzosomal and cationic proteins (p < 0.01) and serum level of total antioxidants (in 46.2 % of the patients compared with 26.3 % under the typical therapy). Three-month treatment with Eurespal in COPD patients resulted in further positive shifts in clinical and laboratory inflammation markers, IS cytological and cytochemical parameters. The results show Eurespal to increase the efficiency of the COPD treatment and could be included in the complex therapy of COPD. It has high antiinflammatory activity, inhibits bronchial obstruction progressing and improves quality of life of COPD patients.Изучали влияние Эреспала (фенспирид) на клиническое течение и показатели воспаления у больных ХОБЛ. Исследование проводили в 2 этапа: в течение 3 нед. терапии при обострении заболевания и на протяжении 3 мес. амбулаторного лечения в период клинической ремиссии. Эреспал назначали в дозе 160 мг в сутки при 2-кратном приеме. Оценивали основные клинические симптомы в баллах, ФВД, данные бронхоскопии, лабораторные показатели воспаления, антиоксидантного статуса, качество жизни (КЖ). Проводили цитологическое и цитохимическое исследование индуцированной мокроты (ИМ). При обострении ХОБЛ терапия Эреспалом оказывала ранний и отчетливый противокашлевый, муколитический эффекты, сопровождалась уменьшением обструкции, интенсивности воспаления в бронхах, достоверным уменьшением С-реактивного белка, снижением цитоза в ИМ, процентного содержания нейтрофилов (р < 0,01) и повышением в них лизосомально-катионных белков (р < 0,01), увеличением общих антиоксидантов в сыворотке крови (у 46,2 % больных, по сравнению 26,3 % в группе традиционной терапии). Длительное (в течение 3 мес.) лечение Эреспалом больных ХОБЛ обеспечивало дальнейшую положительную динамику клинико-лабораторных показателей воспаления, данных цитологического и цитохимического исследования ИМ. Результаты исследования позволяют считать, что включение Эреспала в комплексную терапию ХОБЛ повышает эффективность лечения как при обострении, так и в стадии относительной ремиссии заболевания, оказывая выраженное противовоспалительное действие; предупреждает нарастание обструкции, улучшает КЖ больных

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health

Addition of aluminium, zinc and magnesium hydrides to rhodium(III)

We report the addition of M–H bonds (M = Al, Zn, Mg) to a Rh(III) intermediate generated from the reductive elimination of triethylsilane from [Cp*Rh(H)2(SiEt3)2]. A series of new heterobimetallic complexes possessing Rh–M bonds have been isolated and characterised by a number of spectroscopic (1H, 29Si, 13C, 103Rh NMR, infrared, and X-ray diffraction) and computational techniques (NBO and QTAIM analysis). Experimental and computational data are consistent with cleavage of the M–H bond upon addition to rhodium with formation of new Rh–M and Rh–H bonds. Upon photolysis the Al analogue of this series undergoes a further elimination reaction producing triethylsilane and a highly unusual Rh2Al2H4 containing cluster proposed to contain an Al(I) bridging ligand