1. Reperfusion Without Functional Independence in Late Presentation of Stroke With Large Vessel Occlusion
Fatih Seker, et al. Stroke. 2022 Dec;53(12):3594-3604. doi: 10.1161/STROKEAHA.122.039476. Epub 2022 Oct 14.
Background: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients. Methods: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3). Results: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH. Conclusions: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone. Registration: URL: https://www. Clinicaltrials: gov; Unique identifier: NCT04096248.
2. Acid-base properties of the (1-4,18-36) fragments of neuropeptide K and their mono- and polynuclear copper(II) complexes products of metal-catalyzed oxidation
Marta Błaszak, Elżbieta Jankowska, Teresa Kowalik-Jankowska Inorg Chem. 2013 Jan 7;52(1):130-43. doi: 10.1021/ic301476p. Epub 2012 Dec 17.
Mononuclear and polynuclear complexes of the (1-4,18-36)NPK, Asp(1)-Ala-Asp-Ser(4)-Gly(18)-His(19)-Gly-Gln-Ile-Ser-His(24)-Lys-Arg-His(27)-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met(36)-NH(2), and mononuclear complexes of its acethyl derivative Ac-Asp(1)-Ala-Asp-Ser(4)-Gly(18)-His(19)-Gly-Gln-Ile-Ser-His(24)-Lys-Arg-His(27)-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met(36)-NH(2) have been studied by potentiometric, UV-vis, CD, EPR spectroscopic, and mass spectrometry (MS) methods. As it was observed for other tachykinins (neurokinin A, neuropeptide gamma and its fragments) containing the same C-terminal sequence His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH(2), also for the fragments of neuropeptide K the additional deprotonation most likely on the serine OH group was observed. It is likely that tachykinin peptides contain catalytic Ser/His/Asp triad or dyads Ser/Lys and the serine protease activity. The high water solubility of the resulting metal complexes allowed us to obtain complete complex speciation at different metal-to-ligand ratios ranging from 1:1 to 4:1 for (1-4,18-36)NPK, while only the 1:1 molar ratio was studied for Cu(II)-Ac-(1-4,18-36)NPK because of precipitation. For the metal-to-ligand 1:1 molar ratio the (1-4,18-36)NPK forms in a wide 6.5-10.5 pH range the CuHL complex with a 3N {NH(2),2N(-),β-COO(-)-Asp(3)} binding site. For a metal-to-ligand 1:1 molar ratio at higher pH than 9.5 the dimeric species dominate. For the Ac-(1-4,18-36)NPK peptide the imidazole nitrogen atoms are the primary metal-binding sites forming macrochelates in the pH 4-7.5.
3. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial
Marius M Hoeper, et al. Lancet Respir Med. 2021 Jun;9(6):573-584. doi: 10.1016/S2213-2600(20)30532-4. Epub 2021 Mar 24.
Background: Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.
