7th Drug hypersensitivity meeting: part two

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Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

Low-cost disposable high-pressure setup for in situ X-ray experiments

A low-cost, flexible and fast method to create disposable sample cells suitable for in situ catalytic or material synthesis studies based on standard quartz capillaries, heat-shrinkable tubing and standard Swagelok components is described.doi: 10.1107/S1600577518011165status: publishe

Hyperpolarised Magnetic Resonance of Exchangeable Protons Using Parahydrogen and Aminosilane

Efficient, room temperature hyperpolarisation of exchangeable solvent protons combining parahydrogen (p-H2), ami-nopropyldiethoxymethylsilane (APDMS) and IrCl(COD)(IMES) to generate an active aminosilane-iridium complex, broadens the capabilities of SABRE-type hyperpolarisation of protons. A primary pool of hyperpolarised exchangeable protons transfers its hyperpolarisation to co-solutes with labile protons, partly overcoming the catalytic specificity of SABRE-type spin-transfer catalysis. The silane functionality of APDMS appears to be crucial to the improvement. Their role is unprecedented in p-H2-based hyperpolarisation of nuclear spins and promises to broaden applicability of ultra-sensitive solution-state NMR spectroscopy for the detection and elucidation of molecular behaviors otherwise unde-tectable at conventional sensitivity levels.doi: 10.1021/acs.jpcc.0c01149 Efficient, room temperature hyperpolarisation of exchangeable solvent protons combining parahydrogen (p-H2), ami-nopropyldiethoxymethylsilane (APDMS) and IrCl(COD)(IMES) to generate an active aminosilane-iridium complex, broadens the capabilities of SABRE-type hyperpolarisation of protons. A primary pool of hyperpolarised exchangeable protons transfers its hyperpolarisation to co-solutes with labile protons, partly overcoming the catalytic specificity of SABRE-type spin-transfer catalysis. The silane functionality of APDMS appears to be crucial to the improvement. Their role is unprecedented in p-H2-based hyperpolarisation of nuclear spins and promises to broaden applicability of ultra-sensitive solution-state NMR spectroscopy for the detection and elucidation of molecular behaviors otherwise unde-tectable at conventional sensitivity levels.status: publishe

Enhanced luminescence in ZnAlEu layered double hydroxides with interlamellar carboxylate and β-diketone ligands

The physico-chemical properties of layered double hydroxides (LDHs) can be tailored to a large extent by exploiting the flexibility of their chemical composition. This report describes the synthesis and the detailed quantitative characterization of the luminescence properties of novel Eu3+-containing LDHs intercalated by carboxylate and β-diketonate anionic ligands. To prepare the samples, Zn2+, Al3+ and Eu3+ were coprecipitated in a ligand-rich solution containing 1,3,5-benzenetricarboxylate (BTC), acetylacetonate (ACAC), and thenoyltrifluoroacetonate (TTA). Powder X-ray diffraction is supportive for the intercalation of BTC and ACAC. The presence of TTA is revealed by CHN quantification and by the photoluminescence results. Detailed spectroscopic investigation of these materials demonstrates quantum efficiencies (η) of 15–17% emerging from the symmetry reduction engendered by the organic ligands in the vicinity of Eu3+. Due to (i) the metal-to-ligand proximity provided by the layered structure, (ii) the existence of quasi-resonant electronic states between ligand and metal and (iii) the relaxation of the f-f selection rules caused by the distorted symmetry around Eu3+, these LDHs present enhanced luminescence in comparison to inorganic LDHs intercalated with nitrate.The physico-chemical properties of layered double hydroxides (LDHs) can be tailored to a large extent by exploiting the flexibility of their chemical composition. This report describes the synthesis and the detailed quantitative characterization of the luminescence properties of novel Eu3+-containing LDHs intercalated by carboxylate and β-diketonate anionic ligands. To prepare the samples, Zn2+, Al3+ and Eu3+ were coprecipitated in a ligand-rich solution containing 1,3,5-benzenetricarboxylate (BTC), acetylacetonate (ACAC), and thenoyltrifluoroacetonate (TTA). Powder X-ray diffraction is supportive for the intercalation of BTC and ACAC. The presence of TTA is revealed by CHN quantification and by the photoluminescence results. Detailed spectroscopic investigation of these materials demonstrates quantum efficiencies (η) of 15–17% emerging from the symmetry reduction engendered by the organic ligands in the vicinity of Eu3+. Due to (i) the metal-to-ligand proximity provided by the layered structure, (ii) the existence of quasi-resonant electronic states between ligand and metal and (iii) the relaxation of the f-f selection rules caused by the distorted symmetry around Eu3+, these LDHs present enhanced luminescence in comparison to inorganic LDHs intercalated with nitrate.status: publishe

Erbium enhanced formation and growth of photoluminescent Er/Si nanocrystals

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Photoluminescent Er/Si-nanocrystal composites were obtained after annealing Er doped silicon suboxide (SiOx) thin films. The filmswere prepared by reactive sputtering (Ar/O-2 atmosphere) with a pure silicon target partially covered with metallic Er. The presence of Er in the resulting films strongly influences Si nanocrystal nucleation and growth during thermal treatment at temperatures between 300 and 1300 degrees C. A correlation between Er photoluminescence (PL) spectra, Er speciation and Si nanocrystal properties indicated that PL bands and their intensity are directly influenced by the nanocrystal size and density, and their vicinity to the Er3+ centers. This correlation is explained by considering Er centers as promotor for SiOx disproportionation, locally increasing SiOx concentration which leads to formation of Si-0 nanocrystals in the vicinity of Er. (C) 2013 Elsevier B.V. All rights reserved.536196201Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)LNLS - National Synchrotron Light Laboratory, BrazilFWO-VlaanderenFlemish GovernmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Invasive pulmonary aspergillosis complicating severe influenza: epidemiology, diagnosis and treatment

PURPOSE OF REVIEW: Bacterial super-infection of critically ill influenza patients is well known, but in recent years, more and more reports describe invasive aspergillosis as a frequent complication as well. This review summarizes the available literature on the association of invasive pulmonary aspergillosis (IPA) with severe influenza [influenza-associated aspergillosis (IAA)], including epidemiology, diagnostic approaches and treatment options. RECENT FINDINGS: Though IPA typically develops in immunodeficient patients, non-classically immunocompromised patients such as critically ill influenza patients are at high-risk for IPA as well. The morbidity and mortality of IPA in these patients is high, and in the majority of them, the onset occurs early after ICU admission. At present, standard of care (SOC) consists of close follow-up of these critically ill influenza patients with high diagnostic awareness for IPA. As soon as there is clinical, mycological or radiological suspicion for IAA, antifungal azole-based therapy (e.g. voriconazole) is initiated, in combination with therapeutic drug monitoring (TDM). Antifungal treatment regimens should reflect local epidemiology of azole-resistant Aspergillus species and should be adjusted to clinical evolution. TDM is necessary as azoles like voriconazole are characterized by nonlinear pharmacokinetics, especially in critically ill patients. SUMMARY: In light of the frequency, morbidity and mortality associated with influenza-associated aspergillosis in the ICU, a high awareness of the diagnosis and prompt initiation of antifungal therapy is required. Further studies are needed to evaluate the incidence of IAA in a prospective multicentric manner, to elucidate contributing host-derived factors to the pathogenesis of this super-infection, to further delineate the population at risk, and to identify the preferred diagnostic and management strategy, and also the role of prophylaxis.status: publishe