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

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

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

The original version of this article unfortunately contained a mistake

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

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

Biomarcadores de complicaciones diabéticas en enfermedad y trasplante renal

Tesis doctoral por compendio de publicaciones.Programa de Doctorado en Biomarcadores de Salud y Estados Patológicos por la Universidad de Extremadura.Existen variantes en el gen del receptor de leptina (LEPR) que afectan a los niveles y función de esta citoquina, que a su vez interviene en los niveles de insulina y en el grado de disfunción del riñón en enfermos renales. Nuestro primer objetivo fue estudiar en 315 pacientes trasplantados renales el vínculo existente entre estas variantes genéticas, la PTDM y otros factores fisiológicos implicados. En los siguiente dos trabajos estudiamos marcadores genéticos y no genéticos relacionados con la nefropatía diabética (ND). Existe una necesidad acuciante de nuevos biomarcadores de esta complicación que mejoren su diagnóstico y manejo. Es por ello que medimos en 132 pacientes con ND y 202 controles no diabéticos, los niveles de DHETs en plasma y 20-HETE en orina, con el objetivo de analizar su relación con la enfermedad y con parámetros de función y daño renal. Posteriormente, analizamos en 430 pacientes con ND y 658 controles con función renal normal la influencia de variantes genéticas en genes implicados en la síntesis y metabolismo de estos eicosanoides sobre el desarrollo de la ND y varios parámetros clínicos característicos de la enfermedad. Por último, estudiamos la correlación de los niveles plasmáticos y urinarios de estos eicosanoides con la presencia de polimorfismos en estos mismos genes. Pudimos comprobar que, efectivamente, ciertas variantes genéticas en los genes LEPR, CYP4F2 y CYP2C8, así como los niveles de 20-HETE y DHETs, tienen el potencial de convertirse en biomarcadores eficaces de las complicaciones diabéticas en la enfermedad y el trasplante renal.There are variants in the leptin receptor (LEPR) gene that affect the levels and function of this cytokine, which in turn affects insulin levels and the degree of kidney dysfunction in renal patients. Our first objective was to study the link between these genetic variants, PTDM and other physiological factors involved, in 315 kidney transplant recipients. In the next two works we studied genetic and non-genetic markers related to kidney disease caused by diabetes. There is a pressing need for new biomarkers of this complication that improve its diagnosis and management. That is why we measured in 132 patients with diabetic nephropathy (DN) and 202 non-diabetic controls, the levels of plasma DHETs and urinary 20-HETE, in order to analyze their relationship with the disease and with parameters of function and kidney damage. Subsequently, we analyzed in 430 patients with DN and 658 controls with normal renal function the influence of genetic variants in genes involved in the synthesis and metabolism of these eicosanoids on the development of DN and several clinical parameters characteristic of the disease. Finally, we study the correlation of the plasma and urinary levels of vasoactive eicosanoids with the presence of polymorphisms in these genes. According to our starting hypothesis, we were able to verify that, indeed, certain genetic variants in the LEPR, CYP4F2 and CYP2C8 genes, as well as the levels of 20-HETE and DHETs, have the potential to become accurate biomarkers of diabetic complications in kidney disease and transplantation

Genetics Variants in the Epoxygenase Pathway of Arachidonic Metabolism Are Associated with Eicosanoids Levels and the Risk of Diabetic Nephropathy

Genes in the epoxygenase pathway of arachidonic acid metabolism leading to vasoactive eicosanoids, mainly 20-hydroxyeicosatetraenoic (20-HETE) and epoxyeicosatrienoic (EETs) acids, have been related to glucose-induced renal damage in preclinical reports. We genotyped 1088 diabetic kidney disease (DKD) patients and controls for seven polymorphisms in five genes (CYP2C8, CYP2J2, CYP4F2, CYP4A11, and EPHX2) along this metabolic route and evaluated their effect on DKD risk, clinical outcomes, and the plasma/urine levels of eicosanoids measured by LC/MS/MS and immunoenzymatic assays. The CYP4F2 433M variant allele was associated with lower incidence of DKD (OR = 0.65 (0.48–0.90), p = 0.008), whilst the CYP2C8*3/*3 genotype was related to increased risk (OR = 3.21 (1.05–9.87), p = 0.036). Patients carrying the 433M allele also showed lower eGFR [median and interquartile range vs. wildtype carriers: 30.8 (19.8) and 33.0 (23.2) mL/min/1.73 m2, p = 0.037). Finally, the 433VM/MM variant genotypes were associated with lower urinary levels of 20-HETE compared with 433VV (3.14 (0.86) vs. 8.45 (3.69) ng/mg Creatinine, p = 0.024). Our results indicate that the CYP4F2 V433M polymorphism, by decreasing 20-HETE levels, may play an important role in DKD

Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients

Prostaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (PTGER1-4) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in PTGER1-4 and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two PTGER3 SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07–1.95), p = 0.016 and OR = 0.71 (0.51–0.99), p = 0.041, respectively). In the nephrosclerosis patients, a proximal region of PTGER3 was tagged as relevant for eGFR (p values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive PTGER3 SNPs, rs2284362 and rs2284363, significantly decreased systolic (p = 0.005 and p = 0.0005), diastolic (p = 0.039 and p = 0.005), and pulse pressure values (p = 0.038 and 0.014). Patients were followed for a median of 47 months (7–54) to evaluate cardiovascular (CV) risk. Cox regression analysis showed that carriers of the PTGER1rs2241360 T variant had better CV event-free survival than wild-type individuals (p = 0.029). In addition, PTGER3rs7533733 GG carriers had lower event-free survival than AA/AG patients (p = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk

A Custom Target Next-Generation Sequencing 70-Gene Panel and Replication Study to Identify Genetic Markers of Diabetic Kidney Disease

Diabetic kidney disease (DKD) has been pointed out as a prominent cause of chronic and end-stage renal disease (ESRD). There is a genetic predisposition to DKD, although clinically relevant loci are yet to be identified. We utilized a custom target next-generation sequencing 70-gene panel to screen a discovery cohort of 150 controls, DKD and DKD-ESRD patients. Relevant SNPs for the susceptibility and clinical evolution of DKD were replicated in an independent validation cohort of 824 controls and patients. A network analysis aiming to assess the impact of variability along specific pathways was also conducted. Forty-eight SNPs displayed significantly different frequencies in the study groups. Of these, 28 with p-values lower than 0.01 were selected for replication. MYH9 rs710181 was inversely associated with the risk of DKD (OR = 0.52 (0.28–0.97), p = 0.033), whilst SOWAHB rs13140552 and CNDP1 rs4891564 were not carried by cases or controls, respectively (p = 0.044 and 0.023). In addition, the RGMA rs1969589 CC genotype was significantly correlated with lower albumin-to-creatinine ratios in the DKD patients (711.8 ± 113.0 vs. 1375.9 ± 474.1 mg/g for TC/TT; mean difference = 823.5 (84.46–1563.0); p = 0.030). No biological pathway stood out as more significantly affected by genetic variability. Our findings reveal new variants that could be useful as biomarkers of DKD onset and/or evolution

Polymorphisms in vasoactive eicosanoid genes of kidney donors affect biopsy scores and clinical outcomes in renal transplantation

Cytochrome P450 (CYP) enzymes metabolize arachidonic acid to vasoactive eicosanoids such as epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), whilst soluble epoxide hydrolase, encoded by the EPHX2 gene, is in charge of EETs degradation. We aimed to analyze the influence of common, functional polymorphisms in four genes of the donor on the renal biopsy scores independently assigned by pathologists. Additionally, we examined whether this score or the presence of these SNPs were independent risk factors of clinical outcomes in the first year after grafting. A cohort of 119 recipients and their corresponding 85 deceased donors were included in the study. Donors were genotyped for the CYP4F2 V433M, CYP2C8*3, CYP2J2*7, EPHX2 3'UTR A>G, EPHX2 K55R and EPHX2 R287Q polymorphisms. The association of the donors' SNPs with the biopsy scores and clinical outcomes was retrospectively evaluated by multivariate regression analysis. The CYP2C8*3 polymorphism in the donor was significantly associated with higher scores assigned to pretransplant biopsies [OR = 3.35 (1.03-10.93), p = 0.045]. In turn, higher scores were related to an increased risk of acute rejection [OR = 5.28 (1.32-21.13), p = 0.019] and worse glomerular filtration rate (eGFR) (45.68±16.05 vs. 53.04±16.93 ml/min in patients whose grafts had lower scores, p = 0.010) one year after transplant. Patients whose donors carried the CYP4F2 433M variant showed lower eGFR values (48.96±16.89 vs. 55.94±18.62 ml/min in non-carriers, p = 0.038) and higher risk of acute rejection [OR = 6.18 (1.03-37.21), p = 0.047]. The CYP2J2*7 SNP in the donor was associated with elevated risk of delayed graft function [OR = 25.68 (1.52-43.53), p = 0.025]. Our results taken together suggest that donor genetic variability may be used as a predictor of tissue damage in the graft as well as to predict clinical outcomes and graft function in the recipient.This work has been supported in part by grants PI15/00804 and PI18/00745 from Instituto de Salud Carlos III, Madrid(Spain), and by grants IB16014 (authorGG) and GR18007 from Junta de Extremadura, and Fondo Europeo de Desarrolo Regional (FEDER).Peer reviewe

Polymorphisms in genes involved in vasoactive eicosanoid synthesis affect cardiovascular risk in renal transplant recipients

<p><b>Objective:</b> Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory properties. We aim to determine whether genetic variability in these routes may contribute to cardiovascular (CV) risk in renal transplant recipients.</p> <p><b>Methods:</b> In a cohort of 355 patients, we determined the presence of two polymorphisms, <i>CYP2C8*3</i> and <i>CYP2J2*7</i>, known to affect eicosanoid levels. Associations with CV mortality, CV event-free long-term survival and graft survival were retrospectively investigated by logistic regression models.</p> <p><b>Results:</b><i>CYP2J2*7</i> showed a statistical trend towards higher CV mortality (<i>p</i> = .06) and lower cardiac or cerebral event-free long-term survival (<i>p</i> = .05), whilst <i>CYP2C8*3</i> displayed a significant inverse association with the risk of CV event (hazard ratio [HR] = 0.34 [0.15–0.78], <i>p</i> = .01). The association of <i>CYP2J2*7</i> with CV mortality became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation (HR = 15.72 [2.83–91.94], <i>p</i> = .005). In this subgroup of patients both single nucleotide polymorphisms (SNPs) were significantly associated with event-free survival. HR values were 5.44 (1.60–18.51), <i>p</i> = .007 and 0.26 (0.09–0.75), <i>p</i> = .012 for <i>CYP2J2*7</i> and <i>CYP2C8*3</i>, respectively.</p> <p><b>Conclusions:</b> Our results show, for the first time to our knowledge, that two SNPs in <i>CYP2C8</i> and <i>CYP2J2</i>, which synthesize EETs, may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.</p