14 research outputs found

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Thiolato-bridged arene-ruthenium complexes: synthesis, molecular structure, reactivity and anticancer activity of the dinuclear complexes [(arene)2Ru2(SR)2C12]

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    Treatment of an areneruthenium dichloride dimer with thiols RSH to lead to cationic trithiolato complexes of the type [(arene)2Ru2(SR)3]+ was shown to proceed through the neutral thiolato complexes [(arene)2Ru2(SR)2Cl2], which have been isolated and characterized for arene = p-MeC6H4iPr and R = CH2Ph (1), CH2CH2Ph (2), CH2C6H4-p-tBu (3), and C6H11 (4). The single-crystal X-ray structure analysis of the p-tert-butylbenzyl derivative 3 reveals that the two ruthenium atoms are bridged by the two thiolato ligands without a metalmetal bond. The neutral dithiolato complexes[(arene)2Ru2(SR)2Cl2] (13) are intermediates in the formation of the cationic trithiolato complexes [(arene)2Ru2(SR)3]+ (57). Of the new [(arene)2Ru2(SR)2Cl2] complexes, derivative 2 is highly cytotoxic against human ovarian cancer cells, with IC50 values of 0.20 mu M for the A2780 cell line and 0.31 for the cisplatin-resistant cell line A2780cisR

    Highly cytotoxic trithiophenolatodiruthenium complexes of the type [(η6-p-MeC6H4Pri)2Ru2(SC6H4-p-X)3]+: synthesis, molecular structure, electrochemistry, cytotoxicity, and glutathione oxidation potential

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    A series of cationic dinuclear p-cymene ruthenium trithiophenolato complexes of the type [(eta(6)-p-MeC6H4Pr (i) )(2)Ru-2(SC6H4-p-X)(3)](+) (1 X is H, 2 X is Me, 3 X is Ph, 4 X is Br, 5 X is OH, 6 X is NO2, 7 X is OMe, 8 X is CF3, 9 X is F, 10 X is Pr (i) , 11 X is Bu (t) ) have been synthesized from the reaction of [(eta(6)-p-MeC6H4Pr (i) )RuCl2](2) with the corresponding thiol, isolated as the chloride salts, and further studied for their electrochemical properties, cytotoxicity towards human ovarian cancer cells, and catalytic activity for glutathione (GSH) oxidation. Complex 1 was also compared with the benzene and hexamethylbenzene analogues [(eta(6)-C6H6)(2)Ru-2(SC6H5)(3)](+) (12) and [(eta(6)-C6Me6)(2)Ru-2(SC6H5)(3)](+) (13). The most active compound [11]Cl was structurally studied by single-crystal X-ray diffraction analysis. The concentrations corresponding to 50 % inhibition of cancer cell growth (IC50 values) in the A2780 and A2780cisR cell lines of these complexes except for 6 were in the submicromolar range, complex 11 showing an IC50 value of 0.03 A mu M in both cell lines. The high in vitro anticancer activity of these complexes may be at least partially due to their catalytic potential for the oxidation of GSH, although there is no clear correlation between the IC50 values and the turnover frequencies at about 50 % conversion. However, the cytotoxicity is tentatively correlated to the physicochemical properties of the compounds determined by the electronic influence of the substituents X (Hammett constants sigma (p)) and the lipophilicity of the thiols p-XC6H4SH (calculated log P parameters)

    Competition between glutathione and DNA oligonucleotides for ruthenium(ii) arene anticancer complexes

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    The organometallic anticancer complex [(η6-bip)Ru(en)Cl]+ (1; bip = biphenyl, en = ethylenediamine) selectively binds to N7 of guanine bases of oligonucleotides and native DNA. However, under physiologically relevant conditions (micromolar Ru concentrations, pH 7, 22 mM NaCl, 310 K), the tripeptide glutathione (γ-L-Glu-L-Cys-Gly; GSH) is kinetically competitive with guanine (as guanosine 3′,5′-cyclic monophosphate, cGMP) for coordination with complex 1, and gives rise to a ruthenium thiolato adduct. This thiolato adduct can subsequently undergo oxidation to a sulfenate intermediate, providing a facile route for the formation of a final cGMP adduct via the displacement of S-bound glutathione by G N7 (F. Y. Wang, J. J. Xu, A. Habtemariam, J. Bella and P. J. Sadler, J. Am. Chem. Soc., 2005, 127, 17734). In this work, the competition between GSH and the single-stranded 14-mer oligonucleotide 5′-TATGTACCATGTAT-3′ (I) and duplex III (III = I + II, II = 5′-ATACATGGTACATA) for complex 1 and its analogue [(η6-tha)Ru(en)Cl]+ (2, tha = tetrahydroanthracene) under physiologically relevant conditions was investigated using conventional ESI-MS and high resolution ESI-FTICR-MS coupled to conventional HPLC and nanoscale HPLC, respectively. The results indicate that whether there was high excess of GSH or not in the reaction mixtures, the reaction of complex 1 or 2 with single-stranded oligonucleotide I always gave rise to mono-ruthenated oligonucleotide, and the reaction of complex 1 or 2 with duplex III gave rise to the mono-ruthenated duplex oligonucleotide. Furthermore, the ruthenation of duplex III by complex 1 showed no significant discrimination between the complementary strands I and II, but complex 2 appeared to bind preferentially to strand II compared to strand I as revealed by the high resolution FTICR-MS analysis. GSH is highly abundant in cells at millimolar concentrations and is well known to be involved in the deactivation of the clinical drug cisplatin and in platinum resistance. Our findings reveal a potentially contrasting role for GSH in the mechanism of action of these ruthenium anticancer complexes that may contribute to the lack of cross-resistance with platinum drugs
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