Πρώιμοι δείκτες υπερτασικής νεφροσκλήρυνσης

Η υπερτασική νεφροσκλήρυνση αποτελεί την δεύτερη αιτία, μετά τον διαβήτη, χρόνιας νεφρικής νόσου. Η πάθηση εξελίσσεται αθόρυβα σε ανεπάρκεια νεφρών και η διάγνωσή της είναι δύσκολη διότι δεν εμφανίζονται ειδικά συμπτώματα αλλά ούτε και μορφολογικές αλλοιώσεις στο νεφρικό παρέγχυμα στα αρχικά στάδια της ανάπτυξής της. Επιπλέον, δεν υπάρχουν αξιόπιστοι βιοδείκτες για την έγκαιρη εκτίμηση της νεφρικής βλάβης και οι ασθενείς εκδηλώνουν συμπτώματα όταν σχεδόν το 50% της λειτουργίας των νεφρών έχει χαθεί. Σκοπός της παρούσας διδακτορικής διατριβής είναι να βρεθούν πρώιμοι δείκτες που θα επιτρέπουν την έγκαιρη διάγνωση της υπερτασικής νεφροσκλήρυνσης και να αποσαφηνιστούν οι υποκείμενοι μηχανισμοί που οδηγούν στην εμφάνισή της και οι οποίοι σε μεγάλο βαθμό παραμένουν άγνωστοι. H καλύτερη προσέγγιση για την ανεύρεση τέτοιων πρωτεϊνών-δεικτών σε πολυπαραγοντικές παθολογικές καταστάσεις όπως η υπερτασική νεφροσκλήρυνση είναι η βιολογία συστημάτων και ειδικότερα η πρωτεομική ανάλυση. Καθώς η λήψη βιοψιών νεφρού είναι μια επίπονη εν πολλοίς μη ενδεικνυόμενη διαδικασία έχουν αναπτυχθεί διάφορα ζωικά μοντέλα μελέτης της υπέρτασης. Η μελέτη μας πραγματοποιήθηκε στο ευρέως διαδεδομένο υπερτασικό ζωικό μοντέλο Spontaneously Hypertensive Rat (SHR). Πραγματοποιήθηκαν τρεις διαφορετικές αλλά συμπληρωματικές πρωτεομικές προσεγγίσεις στο νεφρικό παρέγχυμα υπερτασικών SHR και νορμοτασικών WKY (Wistar Kyoto rats) ζώων ηλικίας 6, 13 και 20 εβδομάδων με στόχο την ανάλυση του πρωτεόματος του νεφρού σε βάθος. Από την ανάλυση των αποτελεσμάτων αναγνωρίστηκε πλήθος πρωτεϊνών με διαφορική έκφραση στα υπερτασικά ζώα και με πιθανό κρίσιμο ρόλο στην ανάπτυξη της υπέρτασης. Η βιοπληροφορική ανάλυση κατέδειξε σημαντικά μονοπάτια που απορρυθμίζονται λόγω της υπέρτασης και τα οποία σχετίζονται με το οξειδωτικό στρες, την δυσλειτουργία των μιτοχονδρίων και την απόπτωση. Από τις διαφορικά εκφραζόμενες πρωτεΐνες δύο ήταν εκείνες που παρουσίασαν μεγάλο ενδιαφέρον, η CLIC4 και η SGLT2. Η έκφραση και των δύο αυτών πρωτεϊνών βρέθηκε σημαντικά αυξημένη στα υπερτασικά ζώα όλων των ηλικιών και επιλέχθηκαν ως πιθανοί πρώιμοι δείκτες υπερτασικής νεφροσκλήρυνσης που χρήζουν περαιτέρω μελέτης. Τα ευρήματα της πρωτεομικής επιβεβαιώθηκαν με βιοχημικές και μορφολογικές τεχνικές. Τα αποτελέσματα έδειξαν πως η αυξημένη έκφραση τόσο της CLIC4 όσο και της SGLT2 εντοπίζεται στα επιθηλιακά κύτταρα των εγγύς εσπειραμένων σωληναρίων και ειδικότερα στην ψηκτροειδή παρυφή τους αυξάνοντας την πιθανότητα ότι τα μόρια αυτά μπορεί σε παθολογικές καταστάσεις να εκκρίνονται στα ούρα μέσω εξωσωμάτων. Το γεγονός αυτό σε συνδυασμό με την επιβεβαίωση στο μέλλον των ευρημάτων και σε υπερτασικούς ασθενείς είναι πολύ σημαντικό καθώς μπορεί να ανοίξει το δρόμο σε νέους τρόπους διάγνωσης της υπερτασικής νεφροσκλήρυνσης σε πολύ πρώιμα στάδια και μάλιστα με μη επεμβατικό τρόπο. Συμπερασματικά, τα ευρήματά μας υποδεικνύουν ότι πρώιμες αλλαγές συμβαίνουν στο σωληναριακό διαμέρισμα του νεφρού, και ότι οι αλλαγές αυτές είναι ειδικά εντοπισμένες στα εγγύς εσπειραμένα σωληνάρια. Είναι γνωστό πως τα σωληνάρια διαδραματίζουν σημαντικό ρόλο στην ανθρώπινη νεφρική ανεπάρκεια και την οξεία νεφρική βλάβη ωστόσο, μέχρι τώρα δεν είχαν καταγραφεί τόσο πρώιμες μοριακές μεταβολές. Η μελέτη μας καταγραφεί για πρώτη φορά τέτοιες μεταβολές στα κύτταρα των εγγύς σωληναρίων στο μοντέλο SHR και μάλιστα πριν εκδηλωθούν οι τυπικές παθολογοανατομικές αλλαγές της υπερτασικής νεφροσκλήρυνσης.Hypertension is a strong independent risk factor for Chronic Kidney Disease leading to hypertensive nephrosclerosis. Hypertensive nephrosclerosis, a multifactorial process not well understood, is the second most common cause of end-stage renal disease. In order to elucidate biological processes and macromolecules crucially involved in the development of kidney damage, the application of system biology approaches, like proteomics, is required. Applying proteomic analysis we aimed to identify novel markers associated with the pathogenesis and the development of hypertensive nephrosclerosis at very early stages in the well-established hypertensive animal model Spontaneously Hypertensive Rat (SHR). Blood pressure was measured in conscious SHR and Wistar Kyoto normotensive rat (WKY) animals using a tail-cuff technique. A comprehensive proteomic analysis of total kidney tissue from SHR and WKY animals at 6, 13, and 20 weeks of age was performed by two complementary methods, 2-Dimensional Gel Electrophoresis and Liquid Chromatography – Mass Spectrometry (LC-MS). Furthermore, using the novel technique Laser Capture Microdissection, renal vessels of SHR and WKY animals were isolated to almost total purity from kidney cryo-sections. Proteomic analysis (LC-MS) was performed aiming to detect molecular alterations associated with hypertension exclusively at the renal vessels before the onset of vascular damage. Proteomic analyses in whole kidney parenchyma and in the renal vessels generated a large amount of data that were analysed and compared. A large number (>200) of differentially expressed proteins emerged in hypertensive SHR animals in comparison to normotensive WKY animals. Two of them, CLIC4 and SGLT2, not implicated so far in the development of hypertensive nephrosclerosis were selected for further investigation and validation of proteomic results. Both of these proteins were upregulated in SHR animals at all three time intervals examined. The overexpression of CLIC4 and SGLT2 was confirmed by immunoassays and morphological techniques (western blot, immunohistochemistry, immunofluorescence). The results demonstrated that CLIC4 and SGLT2 were almost exclusively localized at the apical surface of the proximal tubular epithelial cells (brush border). Our studies suggest that major changes occur in the renal parenchyma of SHR animals at very early stages following the development of hypertension. Particularly, these data provide for the first time evidence that hypertension may generate dysfunction at the level of the proximal tubule. The specific localization of CLIC4 and SGLT2 at the luminal surface of proximal tubule epithelial cells raises the possibility that they may be detected in urine samples of hypertensive patients as well. In conclusion, our study suggest possible future use of CLIC4 and SGLT2 as early markers of renal damage during hypertension

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

The Role of Small Airway Disease in Pulmonary Fibrotic Diseases

Small airway disease (SAD) is a pathological condition that affects the bronchioles and non-cartilaginous airways 2 mm or less in diameter. These airways play a crucial role in respiratory function and are often implicated in various pulmonary disorders. Pulmonary fibrotic diseases are characterized by the thickening and scarring of lung tissue, leading to progressive respiratory failure. We aimed to present the link between SAD and fibrotic lung conditions. The evidence suggests that SAD may act as a precursor or exacerbating factor in the progression of fibrotic diseases. Patients with fibrotic conditions often exhibit signs of small airway dysfunction, which can contribute to worsening respiratory symptoms and decreased lung function. Moreover, individuals with advanced SAD are at a heightened risk of developing fibrotic changes in the lung. The interplay between inflammation, environmental factors, and genetic predisposition further complicates this association. The early detection and management of SAD can potentially mitigate the progression of fibrotic diseases, highlighting the need for comprehensive clinical evaluation and research. This review emphasizes the need to understand the evolving connection between SAD and pulmonary fibrosis, urging further detailed research to clarify the causes and potential treatment between the two entities

Brushed DC Motor Drives for Industrial and Automobile Applications with Emphasis on Control Techniques: A Comprehensive Review

The current paper presents an inclusive survey about the AC to DC and DC to DC converters for brushed DC Motor Drives. An essential number of different AC to DC and DC to DC topologies and control techniques, applied on the brushed DC motor drives are presented. This extensive literature review exposes advantages, disadvantages and limitations besides giving the basic operating principles of various topologies and control techniques

Comparative proteomic analysis in microdissected renal vessels from hypertensive SHR and WKY normotensive rats

Systemic hypertension leads to renal damage known as hypertensive nephrosclerosis without obvious clinical symptoms in the initial stages and it has a profound impact on the renal vascular physiology. Despite its major role in End Stage Renal Disease, many aspects of hypertensive nephrosclerosis remain unknown. In order to elucidate the biological pathways and macromolecules deregulated by hypertension, renal vessels were obtained by Laser Capture Microdissection (LCM) from Spontaneously Hypertensive Rats (SHR) and age-matched controls (20 weeks). Proteomic analysis was performed aiming to detect molecular alterations associated with hypertension at the renal vessels before the onset of vascular damage. This analysis identified 688 proteins, of which 58 were differentially expressed (15 up-regulated and 43 down-regulated) in SHR. Many of these proteins are involved in vascular tone regulation by modulating the activity of endothelial Nitric Oxide Synthase (eNOS) (Xaa-Pro aminopeptidase 1 (XPP1), N(G) N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), Dehydropteridine reductase (DHPR)) or in blood pressure control by regulating the renin-angiotensin system (Glutamyl aminopeptidase/Aminopeptidase A (AMPE), Aminopeptidase N (AMPN)). Moreover, pathway enrichment analysis revealed that the eNOS activation pathway is deregulated only in SHR. Our study demonstrates that hypertension causes early proteomic changes in the renal vessels of SHR. These changes are relevant to vascular tone regulation and consequently may be involved in the development of vascular damage and hypertensive nephrosclerosis. Further validation and interference studies to investigate potential therapeutic impact of these findings are warranted

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 (Intensive Care Medicine, (2021), 47, 2, (160-169), 10.1007/s00134-020-06234-9)

The original version of this article unfortunately contained a mistake. The members of the ESICM Trials Group Collaborators were not shown in the article but only in the ESM. The full list of collaborators is shown below. The original article has been corrected