Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies

Background: several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value. Objective: this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI. Methods: a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used. Results: there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled p = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I-2 = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled p = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I-2 = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI. Conclusions: a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored

Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model

The diagnosis of mechanical asphyxia remains one of the most difficult issues in forensic pathology. Asphyxia ultimately results in cardiac arrest (CA) and, as there are no specific markers, the differential diagnosis of primitive CA and CA secondary to asphyxiation relies on circumstantial details and on the pathologist experience, lacking objective evidence. Histological examination is currently considered the gold standard for CA post-mortem diagnosis. Here we present the comparative results of histopathology versus those previously obtained by 1H nuclear magnetic resonance (NMR) metabolomics in a swine model, originally designed for clinical purposes, exposed to two different CA causes, namely ventricular fibrillation and asphyxia. While heart and brain microscopical analysis could identify the damage induced by CA without providing any additional information on the CA cause, metabolomics allowed the identification of clearly different profiles between the two groups and showed major differences between asphyxiated animals with good and poor outcomes. Minute-by-minute plasma sampling allowed to associate these modifications to the pre-arrest asphyxial phase showing a clear correlation to the cellular effect of mechanical asphyxia reproduced in the experiment. The results suggest that metabolomics provides additional evidence beyond that obtained by histology and immunohistochemistry in the differential diagnosis of CA

Cardiopulmonary resuscitation in a swine model of cardiac arrest

Εισαγωγή. Η καρδιοαναπνευστικη ανακοπή (ΚΑ) αποτελεί την πλέον επείγουσα ιατρική κατάσταση. Για να απαντηθούν διάφορα ερωτήματα σχετικά με την ΚΑ, αλλά και για να εφαρμοστούν διάφορα θεραπευτικά πρωτόκολλα, που θα ήταν αδύνατο να πραγματοποιηθούν σε ανθρώπινα θύματα ΚΑ, έχουν χρησιμοποιηθεί διαφορετικά πειραματικά μοντέλα.Σκοπός. Ο σκοπός της παρούσας μελέτης είναι η περιγραφή του πειραματικού μοντέλου ΚΑ και καρδιοαναπνευστικής αναζωογόνησης(ΚΑΑ), που αναπτύχθηκε στο εργαστήριο μας.Υλικά και Μέθοδοι: Μετά από χορήγηση γενικής αναισθησίας και ενδοτραχειακής διασωλήνωσης σε 20 χοίρους, πραγματοποιήθηκε χειρουργική παρασκευή των δυο έσω σφαγίτιδων φλεβών καιτης δεξιάς καρωτίδας. Η πειραματική πρόκληση Κοιλιακής Μαρμαρυγής (KM) προκλήθηκε με απλή επαναφορτιζόμενη μπαταρία λιθίου, μέσω διαφλέβιου βηματοδοτικου καλωδίου, που τοποθετήθηκε στη δεξιά κοιλία. Στη συνέχεια, εφαρμόστηκε το πρωτόκολλο εξειδικευμένης υποστήριξης της ζωής, με τις νέες κατευθυντήριες οδηγίες των διεθνών οργανισμών του 2005. Η συνεχής εντατική παρακολούθηση των πειραματόζωων συνεχίστηκε και μετά 30 min από την ανάκτηση της αυτόματης κυκλοφορίας.Αποτελέσματα: Από τα 20 πειραματόζωα της μελέτης τα 9 ζώα ανέκτησαν αυτόματη κυκλοφορία με την εφαρμογή του πρωτοκόλλου, ενώ στα 11η εφαρμογή του ίδιου πρωτοκόλλου ΚΑΑ δεν ήταν επιτυχής. Επιτυχής αναζωογόνηση συσχετίστηκε με τα επίπεδα πίεσης πλήρωσης των στεφανιαίων αγγείων και της PETC0 2 κατά τη διάρκεια των θωρακικών συμπιέσεων.Συμπεράσματα: Η χρήση μιας κοινής μπαταρίας είναι ένας απλός και αποτελεσματικός τρόπος πρόκλησης KM. Οι αιμοδυναμικές παράμετροι στο χοίρο προσομοιάζουν αυτές του ανθρώπου, καθιστώντας έτσι το ζωικό αυτό είδος κατάλληλο μοντέλο ΚΑΑ.Introduction: Cardiac arrest (CA) is a daunting medical emergency. In order to answer various questions regarding CA, and furthermore to implement novel therapeutic strategies, various animal models have been used.Aim: The aim of the present study is to describe the experimental model of CA and cardiopulmonary resuscitation (CPR), developed in our department.Materials and methods: Twenty pigs were anaesthetized and intubated. The internal jugular veins were surgically prepared, together with the carotid artery. Ventricular fibrillation (VF) was induced with an ordinary lithium battery through a pacing wire inserted into the right ventricle. The animals were resuscitated with the 2005 advanced life support algorythm (ALS), as proposed by International organizations. If the animals restored spontaneous circulation, they were further monitored for 30 minutes.Results: Nine animals restored spontaneous circulation with the implementation of the aforementioned protocol. Successful resuscitation was associated with the coronary perfusion pressure and PETCQ2 during external cardiac compressions.Conclusions: The use of an ordinary lithium battery is a safe and efficient way to induce CA. Swine baseline hemodynamics closely resemble those of human, making the swine model, a favorable model for experimental CA-induction and CPR

The role of nano-perovskite in the negligible thorium release in seawater from Greek bauxite residue (red mud)

We present new data about the chemical and structural characteristics of bauxite residue (BR) from Greek Al industry, using a combination of microscopic, analytical, and spectroscopic techniques. SEM-EDS indicated a homogeneous dominant “Al-Fe-Ca-Ti-Si-Na-Cr matrix”, appearing at the microscale. The bulk chemical analyses showed considerable levels of Th (111 μg g−1), along with minor U (15 μg g−1), which are responsible for radioactivity (355 and 133 Bq kg−1 for 232Th and 238U, respectively) with a total dose rate of 295 nGy h−1. Leaching experiments, in conjunction with SF-ICP-MS, using Mediterranean seawater from Greece, indicated significant release of V, depending on S/L ratio, and negligible release of Th at least after 12 months leaching. STEM-EDS/EELS & HR-STEM-HAADF study of the leached BR at the nanoscale revealed that the significant immobility of Th4+ is due to its incorporation into an insoluble perovskite-type phase with major composition of Ca0.8Na0.2TiO3 and crystallites observed in nanoscale. The Th LIII-edge EXAFS spectra demonstrated that Th4+ ions, which are hosted in this novel nano-perovskite of BR, occupy Ca2+ sites, rather than Ti4+ sites. That is most likely the reason of no Th release in Mediterranean seawater

Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury

Background: Polymyxin B treatment is limited by kidney injury. This study sought to identify Polymyxin B-related urinary metabolomic profile modifications for early detection of polymyxin-associated nephrotoxicity. Methods: Samples were obtained from a previously conducted study. Male Sprague-Dawley rats received dose-fractionated polymyxin B (12 mg/kg/day) once daily (QD), twice daily (BID), and thrice daily (TID) for three days, with urinary biomarkers and kidney histopathology scores determined. Daily urine was analysed for metabolites via 1H nuclear magnetic resonance (NMR). Principal components analyses identified spectral data trends with orthogonal partial least square discriminant analysis applied to classify metabolic differences. Metabolomes were compared across groups (i.e., those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome. Results: A total of 25 rats were treated with Polymyxin B, and n = 2 received saline, contributing 77 urinary samples. Pre-dosing samples clustered well, characterised by higher amounts of citrate, 2-oxoglutarate, and hippurate. Day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite that significantly increased in both BID and TID compared with the QD group. Day 1 taurine correlated with increasing histopathology scores (rho = 0.4167, P = 0.038) and kidney injury molecule-1 (KIM-1) (rho = 0.4052, P = 0.036), whereas KIM-1 on day 1 and day 3 did not reach significance with histopathology (rho = 0.3248, P = 0.11 and rho = 0.3739, P = 0.066). Conclusions: Polymyxin B causes increased amounts of urinary taurine on day 1, which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B

Clinical practice recommendations on the management of perioperative cardiac arrest: A report from the PERIOPCA Consortium

Background: Perioperative cardiac arrest is a rare complication with an incidence of around 1 in 1400 cases, but it carries a high burden of mortality reaching up to 70% at 30 days. Despite its specificities, guidelines for treatment of perioperative cardiac arrest are lacking. Gathering the available literature may improve quality of care and outcome of patients. Methods: The PERIOPCA Task Force identified major clinical questions about the management of perioperative cardiac arrest and framed them into the therapy population [P], intervention [I], comparator [C], and outcome [O] (PICO) format. Systematic searches of PubMed, Embase, and the Cochrane Library for articles published until September 2020 were performed. Consensus-based treatment recommendations were created using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The strength of consensus among the Task Force members about the recommendations was assessed through a modified Delphi consensus process. Results: Twenty-two PICO questions were addressed, and the recommendations were validated in two Delphi rounds. A summary of evidence for each outcome is reported and accompanied by an overall assessment of the evidence to guide healthcare providers. Conclusions: The main limitations of our work lie in the scarcity of good quality evidence on this topic. Still, these recommendations provide a basis for decision making, as well as a guide for future research on perioperative cardiac arrest

Mood and transient cardiac dysfunction in everyday life

Emotion in daily life may be associated with transient myocardial ischemia, ventricular tachycardia and impaired autonomic function in cardiac patients, but the precise temporal sequence is unclear. Eighty-eight patients with suspected coronary artery disease underwent 24-h electrocardiographic monitoring, and affect was measured with the Day Reconstruction Method. Thirteen patients (15%) experienced one or more episodes of ST depression or ventricular tachycardia, nine of whom provided concurrent mood data. Mood and heart rate variability were analyzed for the 15 min before, during, and 15 min after each ST depression/ventricular tachycardia episode, and were compared with control periods not associated with cardiac dysfunction. Patients reported more negative mood in the 15 min preceding cardiac dysfunction compared with control periods (P = 0.02). Heart rate increased in the 5 min before cardiac dysfunction (P = 0.005), whereas low frequency heart rate variability was reduced at onset but not before cardiac dysfunction (P = 0.007). There were not changes in high frequency heart rate variability. This small study indicates that emotional state may contribute to vulnerability of cardiac dysfunction in everyday life