Arterial Blood Samples Research Articles

Accuracy of the Nova StatStrip® glucometer in patients undergoing major abdominal surgery: an observational study.

While the Nova StatStrip® Glucose Hospital Meter System (Nova Biomedical, Waltham, MA, USA) is approved for point-of-care testing (POCT) in critically ill patients, its use during major abdominal surgery has not been evaluated. The purpose of this study was to assess the accuracy of the Nova StatStrip glucometer in patients undergoing major hepatobiliary procedures using the Parkes error grid (ISO15197:2013) and criteria defined by the Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 guideline. This study was a post hoc exploratory study of patients participating in a prospective randomized controlled trial on the effects of hyperinsulinemic normoglycemia (HNC) on infectious outcomes after hepatobiliary surgery. Arterial blood samples were collected before surgery and one hour, two hours, and three hours after baseline. Blood glucose levels were analyzed by the Nova StatStrip glucometer and the GEM® PremierTM 5000 blood gas analyzer. Accuracy of the StatStrip glucometer was assessed using the Parkes error grid for type 1 diabetes mellitus (when 99% of samples were within zones A and B on the Parkes error grid and clinical accuracy was acceptable) and the CLSI POCT12-A3 criteria. Blood glucose levels were analyzed in 135 patients, 70 of whom received the HNC. In the Parkes error grid plotted, all samples at all time-points were within zones A and B. The Nova StatStrip glucometer also satisfied CLSI POCT12-A3 criteria at all time-points. The Nova StatStrip glucometer was accurate in patients undergoing major upper abdominal surgery, independent of the administration of high-dose insulin therapy. ClinicalTrials.gov (NCT01528189); registered 7 February 2012.

Inhibition of bradykinin in SARS-CoV-2 infection: a randomised, double-blind trial of icatibant compared with placebo (ICASARS)

SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently...

Abstract 061: Identification of Proteins Predictive of Post‐Thrombectomy Outcome Based on an Appalachian vs. Non‐Appalachian Cohort

Introduction The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions such as mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non‐Appalachian areas, we set out to identify proteomic biomarkers predictive of stroke outcomes specific to subjects residing in Appalachia. Methods Eighty‐one subjects met inclusion criteria for this study. These subjects underwent MT for ELVO, and during the procedure, carotid arterial blood samples were acquired and subsequently sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT 03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional outcomes (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), cognitive outcomes (Montreal Cognitive Assessment; MoCA), and mortality. Results No significant differences were found in demographic data nor co‐morbidities when comparing Appalachia to non‐Appalachia subjects. However, time from stroke onset to treatment (last known normal) was significantly longer in patients from Appalachia, so this datapoint was entered as a co‐variate in all predictive models. A comprehensive analysis of 184 cardiometabolic and inflammatory proteins revealed seven Appalachia‐specific proteins predictive of NIHSS, fourteen predictive of MoCA, six predictive of mRS, and seven proteins related to mortality. Specifically, within the Appalachian group, the protein multiple epidermal growth factor‐like domains protein 9 (MEGF9) was positively correlated to discharge NIHSS, elevated levels of the proteins coagulation factor XI (F11) and mannose binding protein (MBL2) were found to have an increased likelihood of worse mRS, but there were no proteins identified from the Appalachian cohort that were predictive of worse MoCA score, nor worse mortality. Conclusion Appalachia is an underserved population with significantly worse health disparities, specifically related to ischemic stroke. Our study found that patients who presented from Appalachian regions have a different proteomic response at time of MT when compared to otherwise similar subjects presenting from non‐Appalachian communities. These differentially expressed proteins could be used as prognostic biomarkers as well as novel therapies targeted at an underserved population. Lastly, expression differences may be in part related to environmental exposures, such as coal pollution, which will require additional studies moving forward.

Large animal ventilator-integrated volumetric capnography generates clinically acceptable values of physiologic dead space in anesthetized healthy adult horses.

To evaluate the agreement between the Tafonius large animal ventilator-integrated volumetric capnography (vCap) software and the Respironics NICO noninvasive cardiac output monitor reference system. Data were collected from 56 healthy adult horses undergoing general anesthesia. Animals were placed under general anesthesia and connected to the Tafonius large animal ventilator circle system. A flow partitioning device with CO2 and flow sensors was utilized to couple the endotracheal tube to the NICO monitor. Tafonius CO2 and flow sensors are incorporated into the Y-piece of the breathing circuit. Arterial blood samples were collected to determine the partial pressure of arterial carbon dioxide (PaCO2) immediately before data collection. The PaCO2 was input into the Tafonius and NICO monitor, and dead space ventilation (%Vd), end-tidal CO2 partial pressure (ETco2), mixed-expired CO2 partial pressure (Peco2), and expired tidal volume (Vt) were calculated over a single breath. Multiple measurements were completed for each patient, with a total of 200 paired data points collected for analysis. Data were assessed for normality, and Bland-Altman analysis was performed. Bias and 95% limits of agreement were calculated. The limits of agreement for %Vd of the ventilator-derived measurements fell within ± 10% of the NICO monitor reference method. Our results indicate that, when compared to the NICO monitor method, the Tafonius-integrated vCap software provides clinically acceptable values of Peco2, Vt, and %Vd in healthy adult horses.

Acid-base Status and Electrolyte Changes During Propofol Based General Anesthesia in Patients Undergoing Septoplasty

Propofol is a widely used hypnotic agent globally; however, it may have adverse effects on critical patient outcomes, potentially by interfering with the organ-protective properties of other interventions. Propofol anesthesia can lead to disruptions in metabolic balance. This research aims to examine alterations in acid-base and electrolyte levels during septoplasty surgery when propofol-based anesthesia is administered. In this prospective, observational cohort study, a total of 30 patients between the ages of 18 and 65 with an American Society of Anesthesia physical status I-II were included. Arterial blood samples were collected both before the administration of propofol and five minutes after propofol injection, with the purpose of evaluating the acid-base status and electrolyte parameters including sodium, chloride, calcium and potassium. No cases of acidosis or statistically significant alterations in electrolyte levels were observed in patients following the administration of propofol. Furthermore, none of the patients exhibited any adverse effects such as cardiac failure, rhabdomyolysis, severe metabolic acidosis, or renal failure attributable to propofol during the study. We suggest that the induction dose of propofol for general anesthesia does not lead to metabolic acidosis or electrolyte disturbances. Keywords: Propofol, Arterial, Metabolic acidosis, Anesthesia, Acid-base balance, Potassium, Anion gap

Reliability of Handheld Blood Glucose Monitors in Neonates: Trustworthy Arterial Readings but Capillary Results Warrant Caution for Hypoglycemia.

Accurate glucose monitoring is vitally important in neonatal intensive care units (NICUs) and clinicians use blood glucose monitors (BGM), such as the Inform II, for bedside glucose monitoring. Studies on BGM use in neonates have demonstrated good reliability; however, most studies only included healthy-term neonates. Therefore, the applicability of results to the preterm and/or ill neonate is limited. In preterm and ill neonates, quantify differences in glucose concentrations between (1) capillary glucose (measured by BGM) and arterial glucose (measured by YSI 2300 Stat Plus) and (2) between aliquots from the same arterial blood sample, one measured by BGM versus one by YSI. Forty neonates were included in the study. Using Inform II, we measured glucose concentrations on blood samples simultaneously collected from capillary circulation via heel puncture and from arterial circulation via an umbilical catheter. Plasma was then separated from the remainder of the arterial whole blood sample and a YSI 2300 Stat Plus measured plasma glucose concentration. The dominant majority of arterial BGM results met the Clinical and Laboratory Standard Institute (CLSI) and Food and Drug Administration (FDA) tolerance criteria. Greater discrepancy was observed with capillary BGM values with an average of 27.5% of results falling outside tolerance criteria. Blood glucose monitor testing provided reliable results from arterial blood. However, users should interpret hypoglycemic results obtained from capillary blood with caution.

Arterial Blood Gas, Electrolyte and Acid-Base Values as Diagnostic and Prognostic Indicators in Equine Colic.

The study aimed to investigate if arterial blood analysis in conscious horses presenting with signs of colic and breathing ambient air had diagnostic or prognostic value. Arterial blood samples from 352 horses presenting with colic at a university equine referral hospital were analysed for pH, partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), concentrations of sodium (Na+), potassium (K+), ionised calcium (Ca2+) and chloride (Cl-), actual and standardised plasma bicarbonate concentration (HCO3- (P) and HCO3- (P, st)), blood and extracellular fluid base excess (Base (B) and Base (ecf)) and anion gap (AG). Results were compared to previously reported values for healthy horses, and comparisons were made between final diagnosis, treatment and survival to hospital discharge. Significant differences were found between colic cases and healthy reference values between some primary aetiologies. Overall, surgical and non-surgical colic cases differed in Ca2+ and Cl- concentrations and Ca2+ differed between cases that survived to discharge and those that did not. PaO2 differed between small intestinal surgical cases that survived and those that did not. From these results, we developed regression models that demonstrated excellent or good predictive value in identifying the likelihood of surgical versus medical management and survival to hospital discharge.

Parametric Imaging of P-Glycoprotein Function at the Blood-Brain Barrier Using kE,brain-maps Generated from [11C]Metoclopramide PET Data in Rats, Nonhuman Primates and Humans.

PET imaging using [11C]metoclopramide revealed the importance of P-glycoprotein (P-gp, ABCB1) in mediating the brain-to-blood efflux of substrates across the blood-brain barrier (BBB). In this work, the elimination rate constant from the brain (kE,brain), calculated from dynamic PET images without the need for arterial blood sampling, was evaluated as an outcome parameter for the interpretation of [11C]metoclopramide PET data. kE,brain parameter was obtained by linear regression of log-transformed brain time-activity curves (TACs). kE,brain values (h-1) obtained under baseline conditions were compared with values obtained after complete P-gp inhibition using tariquidar in rats (n = 4) and baboons (n = 4) or after partial inhibition using cyclosporine A in humans (n = 10). In baboons, the sensitivity of kE,brain to measure complete P-gp inhibition was compared with outcome parameters derived from kinetic modeling using a 1-tissue compartment model (1-TCM). Finally, kE,brain-maps were generated in each species using PMOD software. The linear part of the log-transformed brain TACs occurred from 10 to 30min after radiotracer injection in rats, from 15 to 60min in baboons, and from 20 to 60min in humans. P-gp inhibition significantly decreased kE,brain values by 39 ± 12% in rats (p < 0.01), by 32 ± 6% in baboons (p < 0.001), and by 37 ± 22% in humans (p < 0.001). In baboons, P-gp inhibition consistently decreased the brain-to-plasma efflux rate constant k2 (36 ± 9%, p < 0.01) leading to an increase in the total brain volume of distribution (VT, 101 ± 12%, p < 0.001). In all studied species, brain kE,brain-maps displayed decreased P-gp-mediated efflux across the BBB. kE,brain of [11C]metoclopramide provides a simple outcome parameter to describe P-gp function in the living brain when arterial input function data are unavailable, although less sensitive than VT. kE,brain-maps represent easy to compute parametric images reflecting the effect of P-gp on [11C]metoclopramide elimination from the brain.

ARTERIAL CATHETERIZATION IN GREAT APES.

Anesthesia is frequently required to provide appropriate medical care to captive great apes. Anesthetic safety can be optimized through placement of an arterial catheter, which allows direct measurement of arterial blood pressure and easy sampling of arterial blood for blood-gas analysis. Arterial catheterization in great apes can be achieved through palpation-guided or ultrasound-guided placement with or without a modified Seldinger technique. Potential sites for arterial catheterization include the anterior tibial artery, caudal tibial and posterior saphenous arteries, dorsal pedal artery, femoral artery, radial artery, and brachial artery. Arterial catheterization is recommended for lengthy great ape anesthetic procedures or those involving invasive procedures.

Evaluation of procedural pain for neonates in a neonatal intensive care unit: a single-centre study

BackgroundTo evaluate the procedural pain experienced by neonates in a neonatal intensive care unit (NICU) setting and determine the corresponding pain grades.MethodsTwo experienced nurses independently used the Neonatal Infant Pain...

A Novel Filtration Membrane for Clustered Circulating Tumor Cell Extraction: A Prospective Feasibility Study.

Circulating tumor cells (CTCs) have garnered attention as biomarkers for therapeutic response and prognosis in malignant neoplasms. Nonetheless, existing literature predominantly relies on surrogate markers of tumor cells or focuses on single-cell CTC, failing to adequately address the challenge of detecting cluster-forming CTCs, which bear considerable prognostic implications. This prospective study aims to validate the efficacy of a novel filtration membrane, namely Soft Micro Pore Filter (S-MPF®), for rare cell recovery in detecting CTCs through the analysis of clinical samples. Patients with confirmed lung cancer or highly suspected lung cancer based on specific criteria (solid tumor size >2.0 cm, serum carcinoembryonic level >7.5 ng/ml, maximum standard uptake value derived from fluorodeoxyglucose-position emission tomography >2.9) were included in the study. CTCs were extracted from preoperative peripheral arterial blood samples using S-MPF®, and the validity of the filtration system was positively verified. Out of the 25 enrolled patients, 23 had lung cancer. CTC positivity was observed in 17 cases (73.9%), whereas cluster CTC positivity was observed in 16 cases (69.6%), with a median count of two clusters. Single CTC positivity was observed in 11 cases (52.1%), with a median count of one cell. The utilization of the newly developed S-MPF® filtration membrane exhibited a high rate of CTC identification, demonstrating its suitability for clinical applications.

Clinical Characterization of [18F]T-008, a Cholesterol 24-Hydroxylase PET Ligand: Dosimetry, Kinetic Modeling, Variability, and Soticlestat Occupancy.

This series of studies characterized [18F]T-008, a PET radiotracer for imaging cholesterol 24-hydroxylase (CH24H), in healthy volunteers (ClinicalTrials.gov identifier NCT02497235). Assessments included radiation dosimetry, kinetic modeling, test-retest variability (TRT) evaluation, and a dose occupancy evaluation using soticlestat, a selective CH24H inhibitor. Soticlestat is currently in phase 3 development for the treatment of seizures in Dravet syndrome and Lennox-Gastaut syndrome. Methods: In the dosimetry study, 5 participants (3 men) underwent serial whole-body scans to estimate organ-absorbed doses and effective doses of [18F]T-008 using OLINDA/EXM 1.1. For the kinetic modeling and TRT study, 6 participants (all men) underwent two 210-min dynamic [18F]T-008 PET scans with arterial blood sampling. The regional total volume of distribution was estimated using a 1-tissue-compartment model, a 2-tissue-compartment model, and Logan graphic analysis. In the dose occupancy study, 11 participants (all men) underwent 120-min scans at baseline and 2 time points (peak and trough) after receiving single oral doses of soticlestat (50-600 mg). The relationship between effect-site soticlestat concentration and brain occupancy was evaluated with a specially developed pharmacokinetic model and a saturable maximal occupancy model. Results: The estimated mean whole-body effective dose was 0.0292 mSv/MBq (SD, 0.00147 mSv/MBq). [18F]T-008 entered the brain rapidly, with a distribution consistent with known CH24H distribution densities. The 2-tissue-compartment model and Logan graphic analysis best described the tracer kinetics. The mean TRT for estimating total volume of distribution was 7%-15%. Single doses of soticlestat in the range 50-600 mg resulted in occupancies of 64%-96% at 2 h and 11%-79% at 24 h. The estimated half-maximal effect-site concentration of soticlestat was 5.52 ng/mL. Conclusion: [18F]T-008 is a suitable PET radiotracer for quantitatively analyzing CH24H in the human brain. Using [18F]T-008 and PET, we demonstrated that soticlestat was brain-penetrant and established target engagement by displacing [18F]T-008 in a dose-dependent manner in the brain.

DETERMINE PRE-ANALYTICAL ERRORS ' PERCENTAGE IN CLINICAL BIOCHEMISTRY LABS AND DEVELOP REMEDIAL PROCEDURES FOR THEIR PREVENTION

Diagnostic inaccuracies pose a formidable issue in Laboratory Medicine, necessitating immediate initiatives to expand understanding and minimize these discrepancies. Our study delves into the nuances of errors associated with laboratory testing processes, from the test request to result interpretation, underlining the imperative for reducing such errors. Our investigation seeks to identify the incidence of errors in a round-the-clock lab setting over four months, covering pre-analytical, analytical, and post-analytical phases.Over a span period from Jan 2021 to Jan 2022, a broad spectrum of errors within pre-analytical, analytical, and post-analytical phases was methodically logged using a bespoke proforma. The collected data was systematically analyzed utilizing SPSS version 22.All venous and arterial blood samples were processed in the 24-hour lab throughout this period. From the 185,012 samples received, 2,450 were deemed unsuitable for testing, accounting for a 1.32% rejection rate. These samples were disqualified due to an array of pre-analytical errors, including misidentification (0.07%), incorrect tube usage (0.11%), missing samples (0.07%), drawing from an intravenous site (0.10%), inadequate sample volume (0.51%), improper timing of sample collection (0.10%), hemolysed samples (0.31%), and lipemic samples (0.11%).Utilizing an agreed list of evidence-based Quality Indicators, compliant with the current International Standard (ISO 15189:2012), for incorporation into accreditation programs of clinical laboratories stands as a potent approach to augment quality, mitigate error risks, and bolster patient safety.

Coagulofibrinolytic effects of recombinant soluble thrombomodulin in prolonged porcine cardiac arrest

AimTo evaluate coagulofibrinolytic abnormalities and the effects of ART-123 (recombinant human thrombomodulin alpha) in a porcine model of cardiac arrest and prolonged cardiopulmonary resuscitation (CA/CPR). MethodsFifteen pigs (n = 5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR, while 2 pigs underwent sham arrest. CA/CPR animals were randomized to receive saline or 1 mg/kg ART-123 pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Arterial and venous blood samples were drawn at multiple time points for blood gas analysis and measurement of plasma and whole blood markers of coagulation and fibrinolysis. ResultsIn saline-treated CA/CPR, but not sham animals, robust and persistent activation of coagulation and fibrinolysis was observed throughout resuscitation. After 50 minutes of CPR, plasma tests and thromboelastography indicated a mix of hypercoagulability and consumptive coagulopathy. ART-123 had a robust anticoagulant effect, reducing both thrombin-antithrombin (TAT) complexes and d-dimer (p < 0.05 for each). The duration of anticoagulant effect varied depending on the timing of ART-123 administration. Similarly, ART-123 when given prior to cardiac arrest was found to have pro-fibrinolytic effects, increasing free tissue plasminogen activator (tPA, p = 0.02) and decreasing free plasminogen activator inhibitor-1 (PAI-1, p = 0.04). ConclusionA porcine model of prolonged CA/CPR reproduces many of the coagulofibrinolytic abnormalities observed in human cardiac arrest patients. ART-123 demonstrates a combination of anticoagulant and profibrinolytic effects, depending on the timing of its administration relative to cardiac arrest.

A-379 Frequency of Reassignment of Blood Gas Sample Source at a Large Tertiary Care Hospital

Abstract Introduction Arterial blood gases analysis are central to the assessment and management of the critical patient acid-base status and its collection requires expertise and is often collected by trained respiratory therapists, nursing, and medical staff. Venous blood gases, arterialized venous blood gases, and capillary samples are however easier to collect. In this retrospective, study we examined the frequency of reassignment of blood gases results to a different sample type. Method Retrospective review of blood gases results requiring sample type reassignment collected during the last three years from January 2020 to December 2022 were obtained. Results were analyzed for concordance with sampling site and workflow analysis. Results Over the three years study period (2020 to 2022), a total of 196 samples for blood gases analysis required reassignment to a different collection site representing 0.12% of all blood gases testing. Among the 123 initial arterial collections, 72 were reassigned as venous, 40 reassigned to mixed venous sample, and one to capillary collection. Whereas, among the initial 24 venous samples collections 16 were reassigned as arterial and 8 to mixed venous collections. Additionally, among the 25 initial mixed venous collections, 16 were reassigned as arterial, 9 reassigned as venous and 3 were reassigned as capillary collections. The frequency of reassignment from arterial to venous was significantly higher compared to venous to arterial (P &amp;lt; 0.05) or for the reassignment in the mixed venous collections. Although a smaller number of samples were amended to capillary, capillary blood gases reflect arterial samples.There was no significant difference in the frequency of sample type reassignment between the three years of collection with the exception of a slight drop in year 2020 where the majorly of patients were of COVID-19 infection and that collections were likely performed by the same assigned medical personnel. Conclusion Common errors in blood gases collection are failure to obtain an arterial sample and accidental collection of venous samples instead often due to close proximity is common. In this retrospective review, the common reassignment is that of arterial to venous followed by arterial to mixed venous and venous to arterial sample types. Artifactual causes that may lead to misclassification of sample type include sample integrity as exposure to room air falsely reduces pCO2 and elevates pO2 giving a false impression of an arterial collection, similarly, dilution of arterial blood samples by heparin is common (inadequate blood fill of syringe) falsely lowers pCO2 both raising doubt as to the sample type.The impact of reassignment of change of sample type on outcomes and on interpretation requires analysis.

Investigation of the association between oxygen reserve index and arterial partial oxygen pressure in anesthetized dogs

ObjectiveTo evaluate the relationship between oxygen reserve index (ORI) and arterial partial pressure of oxygen (PaO2) in anesthetized dogs. Study designProspective experimental study. AnimalsA total of eight healthy adult Beagle dogs with a median age of 38 (range 20–87) months and a median body mass of 8.6 (range 7.0–13.8) kg. MethodsAfter induction of general anesthesia with propofol, dogs were mechanically ventilated and anesthesia maintained with isoflurane carried in oxygen. Arterial blood samples were collected from a catheter placed in the femoral artery. ORI was measured by placing a CO-oximeter sensor on the tongue. Inspired oxygen fraction (FiO2) was increased from 21% to > 95% in increments of 5%. PaO2 and ORI were recorded and compared at different times. The relationship between ORI and PaO2 was investigated using a nonlinear function, the Hill equation, and a linear regression analysis was performed, as appropriate. ResultsA total of 128 pairs of values were compared for all dogs. Applying the Hill equation to the relationship between ORI and PaO2 resulted in R2 = 0.80 (p < 0.001) with a Hill coefficient of 3.7. It was predicted that ORI ranged 0.1–0.9 as PaO2 ranged 127.0–417.9 mmHg and that in the more linear portion of the range, PaO2 of 127.0–289.9 mmHg ORI ranged 0.1–0.7. Linear regression analysis in the more linear portion showed a weak correlation (R2 = 0.29, p = 0.006). Conclusions and clinical relevanceIn the present study, the Hill equation predicted the relationship between PaO2 and ORI for PaO2 ranging 127.0–417.9 mmHg in anesthetized dogs. However, in the linear portion of the PaO2, the coefficient of determination was low, indicating that ORI is not a surrogate for PaO2.

Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children

BackgroundThe pharmacokinetic properties of the new benzodiazepine remimazolam have been studied only in adults. We investigated the pharmacokinetics of remimazolam after i.v. infusion in anaesthetised paediatric patients. MethodsTwenty-four children (2–6 yr, ASA physical status 1–2, BMI 15–18 kg m−2) undergoing general anaesthesia with sevoflurane were enrolled. During surgery, remimazolam was administered as an i.v. infusion over 1 h at 5 mg kg−1 h−1 for 5 min, followed by 1.5 mg kg−1 h−1 for 55 min. Plasma concentrations of remimazolam and its metabolite CNS7054 were determined from arterial blood samples using ultra-high performance liquid chromatography–mass spectrometry. Pharmacokinetic modelling was performed by population analysis. ResultsPharmacokinetics were best described by a three-compartment model for remimazolam and a two-compartment model for CNS7054 linked by a transit compartment. Remimazolam showed a high clearance of 15.9 (12.9, 18.2) ml kg−1 min−1 (median, Q25, Q75), a small central volume of distribution of 0.11 (0.08, 0.14) L kg−1 and a short terminal half-life of 67 (49, 85) min. The context-sensitive half-time after an infusion of 4 h was 17 (12, 21) min. The metabolite CNS7054 showed a low clearance of 0.89 (0.33, 1.40) ml kg−1 min−1, a small central volume of distribution of 0.011 (0.005, 0.016) L kg−1, and a long terminal half-life of 321 (230, 770) min. ConclusionsRemimazolam in children was characterised by a high clearance and short context-sensitive half-time. When normalised to weight, pharmacokinetic properties were similar to those reported for adults. Clinical trial registrationChiCTR2200057629.

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation.

The global donor kidney shortage crisis has necessitated the use of suboptimal kidneys from donors-after-cardiac-death (DCD). Using an ex vivo porcine model of DCD kidney transplantation, the present study investigates whether the addition of hydrogen sulfide donor, AP39, to University of Wisconsin (UW) solution improves graft quality. Renal pedicles of male pigs were clamped in situ for 30 min and the ureters and arteries were cannulated to mimic DCD. Next, both donor kidneys were nephrectomized and preserved by static cold storage in UW solution with or without AP39 (200 nM) at 4 °C for 4 h followed by reperfusion with stressed autologous blood for 4 h at 37 °C using ex vivo pulsatile perfusion apparatus. Urine and arterial blood samples were collected hourly during reperfusion. After 4 h of reperfusion, kidneys were collected for histopathological analysis. Compared to the UW-only group, UW+AP39 group showed significantly higher pO2 (p < 0.01) and tissue oxygenation (p < 0.05). Also, there were significant increases in urine production and blood flow rate, and reduced levels of urine protein, serum creatinine, blood urea nitrogen, plasma Na+ and K+, as well as reduced intrarenal resistance in the UW+AP39 group compared to the UW-only group. Histologically, AP39 preserved renal structure by reducing the apoptosis of renal tubular cells and immune cell infiltration. Our finding could lay the foundation for improved graft preservation and reduce the increasingly poor outcomes associated with DCD kidney transplantation.

Analysis of circulating ceramides and hexosylceramides in patients with coronary artery disease and type II diabetes mellitus

BackgroundCardiovascular disease (CVD) remains the leading cause of death worldwide. The main driving force behind this association is coronary artery disease (CAD), the manifestation of atherosclerosis in the coronary circulation. Cornerstones in the development of CAD are pathologies in lipid metabolism. In recent years, ongoing research has identified ceramides, a subclass of sphingolipids to be mediators of CVD. The aim of this study is to investigate the influence of type II diabetes mellitus (DM) on circulating ceramides and hexosylceramides (HexCers) in CAD patients.Methods24 patients aged 40–90 years with CAD confirmed by angiography were included into a pilot study. Patients with DM were identified by analysis of discharge letters or other medical documents available at the study center. During coronary angiography, arterial blood samples were collected and quantification of sphingolipids in patient serum was performed by mass spectrometry.ResultsStatistical analysis showed nine significantly different HexCers in CAD patients with DM compared to patients without DM. Among the nine significantly regulated HexCers, we identified seven d18:1 HexCers. This group contributes to the fourth most abundant subgroup of total ceramides and HexCers in this dataset. HexCer-d18:1–23:1(2-OH) showed the strongest downregulation in the patient group with DM.ConclusionThis study suggests that levels of circulating HexCers are downregulated in patients with CAD and concomitant DM compared to patients without DM. Further research is needed to investigate the underlying mechanisms and the suitability of HexCers as possible mediators and/or prognostic markers in CAD.