Classification of amyloidosis by model‐assisted mass spectrometry‐based proteomics

Funding Information: Funding: This research was partly funded by a “Center of Clinical Excellence” research grant from the Health Region of Southern Denmark to Odense Amyloidosis Center (AmyC). Publisher Copyright: © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.Amyloidosis is a rare disease caused by the misfolding and extracellular aggregation of proteins as insoluble fibrillary deposits localized either in specific organs or systemically through-out the body. The organ targeted and the disease progression and outcome is highly dependent on the specific fibril‐forming protein, and its accurate identification is essential to the choice of treat-ment. Mass spectrometry‐based proteomics has become the method of choice for the identification of the amyloidogenic protein. Regrettably, this identification relies on manual and subjective inter-pretation of mass spectrometry data by an expert, which is undesirable and may bias diagnosis. To circumvent this, we developed a statistical model‐assisted method for the unbiased identification of amyloid‐containing biopsies and amyloidosis subtyping. Based on data from mass spectrometric analysis of amyloid‐containing biopsies and corresponding controls. A Boruta method applied on a random forest classifier was applied to proteomics data obtained from the mass spectrometric analysis of 75 laser dissected Congo Red positive amyloid‐containing biopsies and 78 Congo Red negative biopsies to identify novel “amyloid signature” proteins that included clusterin, fibulin‐1, vitronectin complement component C9 and also three collagen proteins, as well as the well‐known amyloid signature proteins apolipoprotein E, apolipoprotein A4, and serum amyloid P. A SVM learning algorithm were trained on the mass spectrometry data from the analysis of the 75 amyloid-containing biopsies and 78 amyloid‐negative control biopsies. The trained algorithm performed su-perior in the discrimination of amyloid‐containing biopsies from controls, with an accuracy of 1.0 when applied to a blinded mass spectrometry validation data set of 103 prospectively collected am-yloid‐containing biopsies. Moreover, our method successfully classified amyloidosis patients ac-cording to the subtype in 102 out of 103 blinded cases. Collectively, our model‐assisted approach identified novel amyloid‐associated proteins and demonstrated the use of mass spectrometry‐based data in clinical diagnostics of disease by the unbiased and reliable model‐assisted classification of amyloid deposits and of the specific amyloid subtype.publishersversionpublishe

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

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