Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

The electronic spectrum of [Pt(tpy)Cl]+ (tpy = 2,2':6',2"-terpyridine) is influenced dramatically by intermolecular stacking interactions in solution and in the solid state. The crystal structure of [Pt(tpy)Cl]ClC>4 (monoclinic, P2\!c (No. 14); a = 7.085(2), b = 17.064(5), c = 26.905(8) Á; ß = 90.0(1)°; Z = 8) consists of discrete Pt2 units (Pt-Pt = 3.269(1) Á) arranged along an infinite tpy-stack (spacing ~3.35 Á). Variable-temperature and concentration studies of the absorption and emission spectra of [Pt(tpy)Cl]+ suggest that similar metal-metal and ligand-ligand interactions persist in the solution phase. The high concentration, low-temperature emission spectrum (5:5:1 ethanol:methanol:DMF) reveals a 740-nm band indicative of -M oligomerization, a 650-nm band attributable to tpy -interactions, and a 470-nm band characteristic of mononuclear [Pt(tpy)Cl]+ -* emission. Concentration-dependent absorption spectra were fit to a "two-dimer" model, yielding equilibrium constants for the formation of Pt-Pt-, and tpy-tpy-bound dimers of 1.3(1) x 10* 123 and 1.0(1) x 103 M-1, respectively, in 0.1 M aqueous NaCl. The low temperature solid-state luminescence of [Pt(tpy)Cl]+ is assigned to a 3(MMLCT) (MMLCT = metal-metal-to-ligand charge transfer) transition. The energy of this band is highly dependent on the counterion (PFe-, CIO4-, Cl-, CF3SO3-), in line with the different colors of these various salts. In contrast, the room-temperature solid-state emission spectra are more difficult to interpret. While the red perchlorate salt exhibits a relatively narrow emission band at 725 nm (red-shifted from the 77-K maximum at 695 nm), consistent with a 3(MMLCT) transition, the orange (Cl-, CIO4-, CF3SO3-) and yellow (PFe-) salts have extremely broad room-temperature emission bands that all appear at nearly the same energy (Amax ~640 nm). We assign this luminescence to an eximeric intraligand transition resulting frominteractions and propose that the temperature dependent emissions from the orange and yellow solid materials originate from multiple electronic states.

Abstract. Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for Ͼ3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P ϭ 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P ϭ 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P ϭ 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with Ͻ3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.The annual mortality rate among patients undergoing maintenance hemodialysis is approximately 18%, with cardiovascular events being the most common cause of death. Morbidity is also substantial, with an average of 1.94 hospitalizations and approximately 14 d of hospitalization each year (1). The HEMO Study was a randomized, prospective, clinical trial designed to examine the effects on clinical outcomes of two treatment parameters, i.e., hemodialysis dose based on the clearance of urea (molecular mass, 60 D) and membrane porosity or flux, which serves...

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[Pt(tpy)Cl]+ (tpy is 2,2‘:6‘,2‘‘-terpyridine) undergoes reversible one-electron reductions in 0.1 M TBAH/DMF (TBAH is tetrabutylammonium hexafluorophosphate) at E° ‘+/0 = −0.74 V and E° ‘0/ - = −1.30 V (vs AgCl (1.0 M KCl)/Ag). The first reduction couple is substantially positive of those observed for other M(II)−tpy complexes (for example, E° ‘0/ - = −1.36 V for [Zn(tpy)Cl2]), a finding that suggests there is coupling between the empty 6p z orbital of square planar Pt(II) and the π* orbital of tpy, stabilizing the (π*)1 radical state. The dimerization constants of both [Pt(tpy)Cl]+ and [Pt(tpy)Cl] in 0.1 M TBAH/DMF were determined spectroelectrochemically and found to be 8(1) × 10 and 10(4) × 10 M-1, respectively. On the basis of variable-concentration studies, a species observed at an intermediate level of reduction is formulated as the mixed-valence dimer [(Pt(tpy)Cl)2]+, with K mix = [(Pt(tpy)Cl)2 +]/([Pt(tpy)Cl+][Pt(tpy)Cl]) = 18(4) × 10 M-1. Analysis of variable-temperature EPR spectra indicates that the first reduction is ligand-centered (2B2) with substantial contributions from Pt(II) 5d yz (4−6%) and 6p z (3−4%). The second reduction is tentatively assigned as metal-centered; 5d x 2 - y 2 is the likely acceptor orbital.

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We report the use of photoinduced electron transfer to drive reductive cleavage of an ester to produce bilayer-forming molecules; specifically, visible photolysis in a mixture of a decanoic acid ester precursor, hydrogen donor molecules, and a ruthenium-based photocatalyst that employs a linked nucleobase (8-oxo-guanine) as an electron donor generates decanoic acid. The overall transformation of the ester precursor to yield vesicles represents the use of an external energy source to convert nonstructure forming molecules into amphiphiles that spontaneously assemble into vesicles. The core of our chemical reaction system uses an 8-oxo-G-Ru photocatalyst, a derivative of [tris(2,2'-bipyridine)-Ru(II)](2+).