Lactate Levels Research Articles

Is it useful to wash stored red blood cells in cardiopulmonary bypass priming fluid for neonatal cardiac surgery? A single-centre retrospective study.

Neonatal cardiac surgery requires careful consideration of cardiopulmonary bypass (CPB) priming fluid composition due to small blood volume and immature physiology. This study investigated the impact of allogeneic stored red blood cells (RBCs) processed using an autotransfusion system in CPB priming fluid for neonates. We compared perioperative parameters, inflammatory mediators, coagulation indicators, vasoactive-inotropic score (VIS) and clinical outcomes between neonates receiving unwashed (n = 56) and washed (n = 45) RBCs in CPB priming fluid. Regression models were used to assess the independent association between RBC washing and patient outcomes. The autotransfusion system improved stored RBC quality. The washed group showed higher peak haematocrit (p < 0.01) and haemoglobin levels (p = 0.04) during CPB, an increased oxygen delivery index during rewarming (p < 0.05) and lower postoperative lactate levels and VIS (p < 0.05). Inflammatory (IL-6, IL-8 and IL-10) and coagulation parameters (D-dimer, fibrinogen and fibrin degradation product) fluctuated compared with baseline but did not significantly differ between groups. The washed group had a lower incidence of hyperlactacidaemia and delayed sternal closure at CPB weaning. Adding washed allogeneic stored RBCs to neonatal CPB priming fluid reduced postoperative lactate elevation and VIS without early improvement in the inflammatory and coagulation systems.

Machine-learning-based evaluation of the usefulness of lactate for predicting neonatal mortality in preterm infants

BackgroundUnlike in adult and pediatric patients, the usefulness of lactate in preterm infants has not been thoroughly discussed. This study aimed to evaluate whether the lactate level in the first hours of life is an important factor associated with neonatal death in very-low-birth-weight (VLBW) preterm infants. MethodsElectronic medical records from a level 4 neonatal intensive care unit in South Korea were reviewed to obtain perinatal and neonatal outcomes. Data on lactate levels of preterm infants in the first 12 h of life were collected. Neonatal mortality and morbidities were compared based on lactate levels. Subsequently, machine-learning models incorporating 20 independent variables, both with and without lactate, were compared for model performances and feature importance of lactate for predicting in-hospital mortality in the applicable models. ResultsOne hundred and sixty-eight preterm infants were included. Death rates on days 7 and 30 of life (D30-mortality) were significantly higher in infants with high lactate levels (≥3rd interquartile range) than in those with lower levels (<3rd interquartile range). Though statistically insignificant, the overall in-hospital mortality was more than twice as high in the high lactate level group than in the lower lactate level group. Based on the machine learning results, Random Forest, Gradient Boosting, and LightGBM models all showed greater area under the curves when lactate was included. Lactate consistently ranked in the variables of top five feature importance, particularly showing the greatest value in the Gradient Boosting model. ConclusionLactate levels during the early hours of life may be an important factor associated with in-hospital death of preterm VLBW infants. Based on the enhanced performance of the above-mentioned machine learning models, lactate levels in the early postnatal period may add to assessing the clinical status and predicting the hospital course in this population.

Utilizing point-of-care lactate testing for rapid prediction of clinical outcomes in patients with acute gastrointestinal bleeding in the emergency department

ObjectivesWe aimed to rapidly predict the prognosis of patients who present to the emergency department (ED) with acute gastrointestinal bleeding (AGIB) using point-of-care (POC) lactate testing. MethodsThis single-center retrospective observational study included 327 patients (survival group, 287; non-survival group, 40) who presented to the ED with AGIB between March 2021 and February 2022. We compared POC-measured lactate levels with laboratory-measured lactate levels using Pearson's correlation. Multivariate logistic regression analysis was used to identify early predictors of in-hospital mortality and correlated clinical outcomes. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff for POC-measured lactate levels for predicting in-hospital mortality, and the ROC curves for POC-measured lactate levels and AIMS65 scores were compared using the DeLong test. ResultsPOC-measured lactate levels strongly correlated with laboratory-measured lactate levels (R2 = 0.82). Patients in the non-survival group had higher POC-measured lactate levels than did those in the survival group (2.6 mmol/L vs. 1.4 mmol/L, p < 0.001). POC-measured lactate level, age, systolic blood pressure, heart rate, and malignancy were identified as early predictors of in-hospital mortality (adjusted odds ratio [aOR] for POC-measured lactate levels: 1.15; 95 % confidence interval [CI] 1.02–1.30). The optimal POC-measured lactate level cutoff was 3.2 mmol/L. Areas under the ROC curves for POC-measured lactate level and the AIMS65 score were 0.70 and 0.73, respectively, showing statistical compatibility. Higher POC-measured lactate levels correlated with ICU admission, blood transfusion, and mechanical ventilation (aOR: 1.16, 95 % CI 1.05–1.27; 1.16, 1.04–1.30; and 1.31, 1.13–1.53, respectively]. Further, the hyperlactatemia subgroup (POC-measured lactate level ≥3.2 mmol/L) exhibited a lower survival probability in the Kaplan–Meier survival analysis (p < 0.01). ConclusionsOur study shows that rapidly obtainable POC-measured lactate levels are valuable for predicting critical outcomes in AGIB patients and should be considered an early prognostic indicator for in-hospital mortality in the ED.

O96 NICD LACTYLATION OF NOTCH SIGNALING IMPROVES MICROVASCULATION RAREFACTION IN HYPERTENSION

Background and Objective: Microvascular rarefaction is a key pathophysiologic basis of hypertension-related cardiovascular disease. Exercise decreases blood pressure and promotes angiogenesis related to inhibition of NOTCH signaling. The activation of the NOTCH pathway depends on the transcriptional regulation of its intracellular active fragment NICD after nuclear translocation. The post-translational modification status of proteins plays a crucial role in the nuclear translocation effect of transcription factors. Lactylation is influenced by the level of lactate in the body. Exercise can promote glycolysis in endothelial cells, and increase intracellular lactate levels. Therefore, we explored whether the beneficial effects of Exercise were mediated by promoting NICD lactylation, inhibiting the NOTCH signaling, and promoting angiogenesis. Methods: To test our hypotheses, WKYs (normotensive rats) and SHRs (spontaneously hypertensive rats) were given exercise for 12 weeks. Blood pressure was determined by the tail-cuff method, and cardiac function was assessed by echocardiography. Using rats’ retina, gastrocnemius, and myocardium detected microvascular density. The expression levels of NOTCH signaling pathway related proteins and angiogenesis related factors were measured by Western Blotting. The level of lactate was measured by using a lactate assay kit. Protein modification omics was used to detect the modification types and levels of NICD in microvascular endothelial cells, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to detect the lactylation sites of NICD in microvascular endothelial cells. Results: Exercise in SHRs resulted in reduced blood pressure and concentric hypertrophy. Exercise promoted angiogenesis and improved microcirculation rarefaction. Exercise also reduced the production of NOTCH pathway related proteins and increased the expression level of angiogenesis related factors. The lactate level increased after exercise, and the lactylation level of NICD increased. Conclusions: In summary, Exercise decreases hypertension and improves cardiac function in SHRs. Our research results indicated that exercise increases lactate production and induces NICD lactylation, thereby inhibiting the NOTCH signaling, upregulating the expression of angiogenic factors, promoting angiogenesis, and lowering blood pressure.

The effects of pathogen reduction technology on apheresis platelet concentrates stored in PAS.

The impact of pathogen reduction technology (PRT) such as Mirasol, and the effect of platelet additive solutions (PAS) on the activity and hemostatic profile of transfused apheresis platelets remain largely unknown. The aim of this study was to assess the in vitro hemostatic and metabolic profile of Mirasol treated platelets in PAS during a 7-day storage period. Ten split bags containing apheresis platelets stored in PAS were split into two groups; control platelets (No.=10 units) and PRT-treated platelets (No.=10 units). In vitro evaluation of the platelet components was performed on the 1st, 3rd, 5th, and 7th days of the storage period. Several metabolic parameters including pH, glucose, and lactate levels were evaluated, while assessment of their hemostatic capacity was performed using light transmission aggregometry (LTA) and viscoelastic studies such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG). Last, Annexin V levels were measured though flow cytometry for evaluation of platelet activation. Clot strength, as reflected by the maximum clot firmness (MCF) and the maximum amplitude (MA) parameters of the viscoelastic studies was significantly decreased in the PRT-treated platelets compared to the control platelets (p<0.05). Clot strength based on MCF and MA values was also found to be decreasing over storage time in PRT-treated platelets (p<0.001), while this was not evident in control platelets. Moreover, the comparison between pH, glucose, and lactate levels were indicative of increased metabolic activity in PRT-treated platelets compared to control platelets (p<0.001). Last, Annexin-V was significantly higher in PRT-treated platelets compared to control platelets on the 7th day of the storage period (p<0.001). The results of this study indicate that increased PSL induced by PRT treatment leads to a decreased in vitro platelet hemostatic efficacy and increased metabolic activity. However, the clinical impact of these alterations needs further investigation.

Hematocrit and Albumin Levels at Admission Predict in-Hospital Mortality in Pediatric COVID-19 Omicron Variant Patients.

The Omicron variant is the present predominant COVID-19 strain worldwide. Accurate mortality prediction can facilitate risk stratification and targeted therapies. The study aimed to evaluate the feasibility of the difference in hematocrit and albumin (HCT-ALB) levels, alone or combined with the pediatric Sequential Organ Failure Assessment (pSOFA) score and lactate level, to predict the in-hospital mortality of COVID-19 Omicron variant-infected pediatric patients. A multicenter retrospective cohort study was performed for children with COVID-19 Omicron variant infection between December 2021 and January 2022. The demographics, clinical characteristics, hospital admission laboratory test results, and treatments were recorded. The in-hospital mortality was documented. The associations between HCT-ALB levels and mortality, and between HCT-ALB+pSOFA+lactate and mortality were analyzed. A total of 119 children were included. The median age was 1.6 (interquartile range: 0.5-6.2) years old. There were 70 boys and 49 girls. The mortality rate was 14.3% (17/119). The univariate and multivariate Cox regression analysis revealed that HCT-ALB was associated to in-hospital mortality (hazard ratio: 1.500, 95% confidence interval: 1.235-1.822, p<0.001). The receiver operating characteristic curve analysis revealed that HCT-ALB can be used to accurately predict in-hospital mortality at a cut-off value of -0.7 (area under the curve: 0.888, sensitivity: 0.882, specificity: 0.225, Youden index: 0.657, p<0.001). These patients were assigned into three groups based on the HCT-ALB level, pSOFA score, and lactate level (low-, medium-, and high-risk groups). The Kaplan-Meier analysis revealed that the mortality increased in the high-risk group, when compared to the medium-risk group (p<0.01). The latter group had a higher mortality, when compared to the low-risk group (p<0.01). The HCT-ALB level can be applied to predict the in-hospital mortality of children infected with the COVID-19 Omicron variant. Its combination with other variables can improve prediction performance.

Association of Weight-indexed Conventional Ultrafiltration Volume with Post-operative Lactate in Patients Undergoing Cardiopulmonary Bypass.

Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) is utilized to minimize hemodilution. However, removing high volumes leads to tissue hypoperfusion by activating the anaerobic glycolysis pathways. This study aimed to determine the association between weight-indexed CUF volumes and lactate in patients who underwent coronary artery bypass grafting (CABG). In this single-center retrospective study, 641 CABG patients, who were referred to Al-Zahra Hospital (Shiraz, Iran) and underwent CPB, during 2019-2021, were recruited. Peri-operative parameters were extracted from the patient's records. The patients with non-elective status, pre-existing liver and renal diseases, ejection fraction<35%, and repeated sternotomy were excluded from the study. An increase in post-operative lactate level≥4 mmol/L after 6 hours was defined as hyperlactatemia (HL). To predict HL, univariable and multiple logistic regression modeling, while controlling confounding factors, were employed. The patients' mean age was 58.8±11.1 years, and 39.2% were women. The incidence of HL was 14.5% (93 patients). There was a significant association between weight-indexed CUF volume and HL. The volume removed in the HL patients was almost doubled (43.37±11.32 vs. 21.41±8.15 mL/Kg, P<0.001), and the higher the weight-indexed CUF volume, the more likely to develop an HL at a rate of 1.38 (Odds ratio=1.38 [1.27-1.49], 95% CI, P<0.001). Furthermore, the multiple logistic regression model showed that HL was associated with the lowest mean arterial pressure (MAP) during CPB. A higher volume of ultrafiltration was associated with increased post-operative serum lactate levels.

Potential Impact of Direct Versus Indirect Central Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) Cannulation in Refractory Postcardiotomy Cardiogenic Shock.

Background Central venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a commonly employed strategy to support patients in refractory postcardiotomy cardiogenic shock (RPCS). This support can be provided using either indirect central ECMO (icECMO) with a closed thorax or direct central ECMO (dcECMO) with an open thorax. Methods This single-center retrospective analysis included 60 patients undergoing central VA-ECMO for RPCS from January 2019 to December 2020. The primary endpoint of this study is to compare 30-day survival outcomes between the icECMO and dcECMO approaches in RPCS patients. Secondary endpoints include the evaluation of adverse events and the identification of predictors that influence 30-day mortality. Results The study included 60 patients, 25 received icECMO and 35 treated with dcECMO due to RPCS. The icECMO group demonstrated significantly better 30-day survival rates (icECMO; 10 [40%] vs. dcECMO; 5 [14.3%], log-rank test; p=0.042). Despite comparable ECMO flow rate and ECMO RPM (rotations per minute) in the first day between the study groups ([icECMO; 4.5 l/min vs. dcECMO; 4.6 l/min, p=0.124], [icECMO; 3510 rpm vs. dcECMO; 3800 rpm, p=0.115], respectively), lactate levels were significantly higher in the dcECMO group on the 1st and 3rd post-extracorporeal life support (ECLS) days (p=0.006 and p=0.008, respectively). Gastrointestinal ischemia was more common in the dcECMO group (p=0.036). Successful ECMO weaning was more frequent in the icECMO group (56% vs. 22.9%, p=0.014). Multivariable logistic regression identified arterial lactate on the first day with a cutoff 4 mmol/las an independent risk factor for 30-day mortality with Exp(B) of 8.9 (p=0.007). Conclusions Our findings suggest a potential survival advantage with the icECMO technique in patients undergoing central ECMO cannulation after RPCS. However, larger prospective studies are essential to confirm this observation.

Circulating factors, in both donor and ex-vivo heart perfusion, correlate with heart recovery in a pig model of DCD

BackgroundHeart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. MethodsCirculatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. ResultsCirculating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min. ConclusionsIn heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

Advances in textile-based microfluidics for biomolecule sensing.

Textile-based microfluidic biosensors represent an innovative fusion of various multidisciplinary fields, including bioelectronics, material sciences, and microfluidics. Their potential in biomedicine is significant as they leverage textiles to achieve high demands of biocompatibility with the human body and conform to the irregular surfaces of the body. In the field of microfluidics, fabric coated with hydrophobic materials serves as channels through which liquids are transferred in precise amounts to the sensing element, which in this case is a biosensor. This paper presents a condensed overview of the current developments in textile-based microfluidics and biosensors in biomedical applications over the past 20 years (2005-2024). A literature search was performed using the Scopus database. The fabrication techniques and materials used are discussed in this paper, as these will be key in various modifications and advancements in textile-based microfluidics. Furthermore, we also address the gaps in the application of textile-based microfluidic analytical devices in biomedicine and discuss the potential solutions. Advances in textile-based microfluidics are enabled by various printing and fabric manufacturing techniques, such as screen printing, embroidery, and weaving. Integration of these devices into everyday clothing holds promise for future vital sign monitoring, such as glucose, albumin, lactate, and ion levels, as well as early detection of hereditary diseases through gene detection. Although most testing currently takes place in a laboratory or controlled environment, this field is rapidly evolving and pushing the boundaries of biomedicine, improving the quality of human life.

Hepato-splanchnic fluxes during exercise in patients with cirrhosis-a pilot study.

In cirrhotic patients, compromised hepatocyte function combined with disturbed hepatic blood flow could affect hepato-splanchnic substrate and metabolite fluxes and exacerbate fatigue during exercise. Eight cirrhotic patients performed incremental cycling trials (3 × 10 min; at light (28 [19-37] W; median with range), moderate (55 [41-69] W), and vigorous (76 [50-102] W) intensity). Heart rate increased from 68 (62-74) at rest to 95 (90-100), 114 (108-120), and 140 (134-146) beats/min (P < 0.05), respectively. The hepatic blood flow, as determined by constant infusion of indocyanine green with arterial and hepatic venous sampling, declined from 1.01 (0.75-1.27) to 0.69 (0.47-0.91) L/min (P < 0.05). Hepatic glucose output increased from 0.6 (0.5-0.7) to 1.5 (1.3-1.7) mmol/min, while arterial lactate increased from 0.8 (0.7-0.9) to 9.0 (8.1-9.9) mmol/L (P < 0.05) despite a rise in hepatic lactate uptake. Arterial ammonia increased in parallel to lactate from 47.3 (40.1-54.5) to 144.4 (120.5-168.3) μmol/L (P < 0.05), although hepatic ammonia uptake increased from 19.5 (12.4-26.6) to 69.5 (46.5-92.5) μmol/min (P < 0.05). Among the 14 amino acids measured, glutamate was released in the liver, while the uptake of free fatty acids decreased. During exercise at relatively low workloads, arterial lactate and ammonia levels were comparable to those seen in healthy subjects at higher workloads, while euglycemia was maintained due to sufficient hepatic glucose production. The accumulation of lactate and ammonia may contribute to exercise intolerance in patients with cirrhosis.

Biomarkers of oxidative stress, biochemical changes, and the activity of lysosomal enzymes in the livers of rainbow trout (Oncorhynchus mykiss Walbaum) vaccinated against yersiniosis before a Yersinia ruckeri challenge

Abstract Introduction This study aimed to evaluate biomarkers of oxidative stress (2-thiobarbituric acid reactive substances, aldehyde and ketone derivatives of oxidatively modified proteins and total antioxidant capacity), the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase), that of lysosomal enzymes (alanyl aminopeptidase, leucyl aminopeptidase, β-N-acetylglucosaminidase and acid phosphatase) and changes in biochemical parameters (alanine aminotransferase, aspartate aminotransferase, de Ritis ratio, lactate dehydrogenase activity, lactate and pyruvate levels and their ratio) in the liver tissue of fish that were vaccinated against enteric redmouth disease and challenged with its causative agent, the bacterium Yersinia ruckeri. Material and Methods The vaccine was administered orally to trout, some of which were challenged with Y. ruckeri 61 days later. For comparison, unvaccinated and unchallenged trout and unvaccinated and challenged trout were also evaluated. Results In the unvaccinated fish, infection with Y. ruckeri disrupted the pro-oxidant/antioxidant balance, led to a significant increase in lipid peroxidation and oxidative modification of proteins, decreased total antioxidant capacity and significantly increased the activity of lysosomal enzymes. In vaccinated fish, the Y. ruckeri challenge increased the activity of glutathione-related enzymes and decreased lipid peroxidation, anaerobic metabolism and the activity of lysosomal enzymes in fish livers relative to the unvaccinated and challenged group. In contrast, these parameters increased after the Y. ruckeri challenge in unvaccinated trout relative to those in the untreated group. Conclusion Vaccination exerted a protective effect during the Y. ruckeri challenge and had no adverse effect on fish livers.

Body condition of stranded Razorbills and Atlantic Puffins in the Western Mediterranean.

Annual mass migrations of seabirds between their breeding and wintering grounds are critical for ensuring their survival and reproductive success. It is essential to comprehend their physical condition in order to identify the causes of death and to facilitate conservation efforts. This study focuses on evaluating the age, body condition index, and metabolites in liver and muscle (triglycerides, glycerol, glycogen, cholesterol, lactate, and glucose) of stranded Razorbills (n = 84) and Atlantic puffins (n = 11). The study was conducted along the Andalusian coast of Spain during the winter season of 2022-2023. The study examined the body condition of stranded individuals and their metabolic state to determine potential factors that may have caused their deaths. The study found that the majority of stranded individuals were juveniles. Both species exhibited low levels of carbohydrate (glucose and glycogen) in their tissues and high levels of lactate in their muscles. These findings could suggest that the individuals had undergone prolonged, strenuous exercise, demanding energy on anaerobic pathways, which may have been associated with migration. The study highlights the significance of adhering to standardized protocols when assessing the body condition of stranded seabirds. Doing so can help to identify causes of death and facilitate conservation efforts. A proposed index for body condition, which incorporates biometric measurements and individual physical condition, provides a comprehensive means of understanding the health of these unique species. This study underscores the importance of further research into the conservation measures and recommendations for protecting seabird populations. It is critical to comprehend the contributing factors of mass mortality incidents to work towards safeguarding these species and preserving their vital migration patterns.

Neurodevelopmental Outcomes of Pediatric Cardiac Extracorporeal Membrane Oxygenation Survivors With Central Cannulation.

Extracorporeal life support, such as pediatric cardiac extracorporeal membrane oxygenation (ECMO), is associated with significant mortality and morbidity risk. This study evaluated cardiac ECMO survivors with central cannulation and found that 51.1% were discharged from the hospital. The study also revealed high rates of developmental delay (82.7%), motor dysfunction (58.8%), and cognitive dysfunction (70.6%) among survivors. No significant correlation was found between the duration of ECMO, age at ECMO, pre-ECMO maximum lactate levels, and cognitive scores. Participants with motor dysfunction were significantly younger (p = 0.04). PRISM scores of those with an abnormal developmental status were significantly higher (p = 0.03). Logistic regression analysis did not show a significantly increased risk. Factors such as age, disease severity, and ECMO itself were identified as potential contributors to neurodevelopmental delay.

Umbilical arterial blood lactate as predictor of early neonatal outcome and evaluation of intrapartum asphyxia

BackgroundPerinatal asphyxia is a leading cause of under-5 mortality and exerts great pressure on the health system. Adequate foetal monitoring in labour is paramount in the early detection of foetal distress to prevent perinatal asphyxia. Several methods of foetal monitoring are in use with varying efficacy. This study investigated the efficacy of umbilical arterial (UA) lactate assay in predicting adverse perinatal outcomes. MethodologyThis was a prospective longitudinal study involving 160 pregnant women in the active phase of labour at term who met the inclusion criteria. They were recruited using a consecutive sampling technique and underwent a cardiotocography. Then they were classified into normal and abnormal cardiotocographic groups. At delivery, the UA blood of all of the babies was collected and assayed for serum lactate, and the levels were correlated with the perinatal outcome. The perinatal outcomes were measured by Apgar scores, admission into the neonatal unit, and hypoxic ischaemic encephalopathy. Analysis was done to determine the sensitivity and specificity of UA lactate in predicting birth asphyxia, hypoxic ischaemic encephalopathy, and neonatal unit admission. ResultsThe mean age ± standard deviation (SD) between the two cardiotocography (CTG) groups, normal years (30.55 ± 5.59) and abnormal years (29.86 ± 5.51), were similar. A critical UA lactate concentration > 9.1 mmol/L predicted Apgar scores < 7 at 5 min with a sensitivity and specificity of 76.47% (CI: 50.1–93.2) and 91.55% (CI: 85.7–95.6%), respectively. Also, the need for neonatal unit admission was predicted at a cut-off point >9.1 mmol/L with a sensitivity of 61.90% (CI: 38.4–81.9) and specificity of 91.30% (CI: 85.3–95.4). Umbilical artery lactate levels > 11.2 mmol/L predicted the development of hypoxic ischaemic encephalopathy in neonates with a sensitivity of 100% (CI: 39.8–100.0) and specificity of 88.39% (CI: 82.3–93.0). ConclusionUmbilical artery lactate correlates with adverse pregnancy outcomes and is an excellent tool for predicting adverse neonatal outcome.

Infusion of 20% Human Albumin Reduces the Requirement of Intraoperative Intravenous Fluids in Patients Undergoing Open Gastrointestinal Oncosurgeries – A Randomised Controlled Study

Background and Aims: The optimal strategy for intraoperative fluid management in patients undergoing major abdominal oncosurgery remains undecided. The present study was undertaken to determine the effect of 20% intravenous (IV) albumin on the requirement of IV fluids (IVFs) during open gastrointestinal (GI) cancer surgeries. Methods: This randomised, double-blinded, controlled trial was conducted in a tertiary care centre from August to October 2022 after obtaining approval from the institutional ethics committee and informed written consent from the study subjects. Forty patients were randomised to either Group A (n = 20), receiving an IV infusion of 25 mL/h of 20% albumin, or Group C (n = 20), receiving an IV infusion of 25 mL/h of plasmalyte for 4 h (total 100 mL). Fluid and vasopressor administration was guided by systemic and pulse pressure variations. The primary outcome was the intraoperative requirement for IVF in the two study groups. The secondary outcomes included intraoperative IV vasopressor requirement, serum lactate levels, incidence of post-operative complications and length of hospital stay. Results: After the exclusion of three patients due to intraoperative bleeding, 37 patients were included in the final analysis. Patients in Group A (n = 19) required less IVF (3.92 ± 0.54 mL/kg/h) as compared to Group C (n = 18) (5.03 ± 1.20 mL/kg/h) (P &lt; 0.001). Four patients (22%) in Group C required intraoperative noradrenaline IV infusion (P = 0.040). There was no significant difference between the two groups, regarding the mean intraoperative serum lactate values, incidence of post-operative complications and mean length of hospital stay (P &gt; 0.05). Conclusions: A 100 mL of 20% human albumin as an IV infusion over 4 h reduced the requirement of IV fluid and vasopressor intraoperatively in patients undergoing open GI cancer surgery.

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate-mediated lactylation of microglia-related proteins on spinal cord injury.

Spinal cord injury (SCI) results in significant neurological deficits, and microglia play the critical role in regulating the immune microenvironment and neurological recovery. Protein lactylation has been found to modulate the function of immune cells. Therefore, this study aimed to elucidate the effects of glycolysis-derived lactate on microglial function and its potential neuroprotective mechanisms via lactylation after SCI. Single-cell RNA sequencing (scRNA-seq) data were obtained from figshare to analyze cellular and molecular alterations within the spinal cord post-SCI, further focusing on the expression of microglia-related genes for cell sub-clustering, trajectory analysis, and glycolysis function analysis. We also evaluated the expression of lactylation-related genes in microglia between day 7 after SCI and sham group. Additionally, we established the mice SCI model and performed the bulk RNA sequencing in a time-dependent manner. The expression of glycolysis- and lactylation-related genes was evaluated, as well as the immune infiltration analysis based on the lactylation-related genes. Then, we investigated the bio-effects of lactate on the inflammation and polarization phenotype of microglia. Finally, adult male C57BL/6 mice were subjected to exercise first to increase lactate level, before SCI surgery, aiming to evaluate the protective effects of lactate-mediated lactylation of microglia-related proteins on SCI. scRNA-seq identified a subcluster of microglia, recombinant chemokine C-X3-C-motif receptor 1+ (CX3CR1+) microglia, which is featured by M1-like phenotype and increased after SCI. KEGG analysis revealed the dysfunctional glycolysis in microglia after SCI surgery, and AUCell analysis suggested that the decreased glycolysis an increased oxidative phosphorylation in CX3CR1+ microglia. Differential gene analysis suggested that several lactylation-related genes (Fabp5, Lgals1, Vim, and Nefl) were downregulated in CX3CR1+ microglia at day 7 after SCI, further validated by the results from bulk RNA sequencing. Immunofluorescence staining indicated the expression of lactate dehydrogenase A (LDHA) in CX3CR1+ microglia also decreased at day 7 after SCI. Cellular experiments demonstrated that the administration of lactate could increase the lactylation level and inhibit the pro-inflammatory phenotype in microglia. Functionally, exercise-mediated lactate production resulted in improved locomotor recovery and decreased inflammatory markers in SCI mice compared to SCI alone. In the subacute phase of SCI, metabolic remodeling in microglia may be key therapeutic targets to promote nerve regeneration, and lactate contributed to neuroprotection after SCI by influencing microglial lactylation and inflammatory phenotype, which offered a novel approach for therapeutic intervention.

Extracorporeal cardiopulmonary resuscitation for pediatric out-of-hospital cardiac arrest: A review of the Extracorporeal Life Support Organization Registry

AimsCurrent data are insufficient for the leading resuscitation societies to advise on the use of extracorporeal cardiopulmonary resuscitation (ECPR) for pediatric out-of-hospital cardiac arrest (OHCA). The aim of this study was to explore the current utilization of ECPR for pediatric OHCA and characterize the patient demographics, arrest features, and metabolic parameters associated with survival. MethodsRetrospective review of the Extracorporeal Life Support Organization Registry database from January 2020 to May 2023, including children 28 days to 18 years old who received ECPR for OHCA. The primary outcome was survival to hospital discharge. ResultsEighty patients met inclusion criteria. Median age was 8.8 years [2.0–15.8] and 53.8% of patients were male. OHCA was witnessed for 65.0% of patients and 46.3% received bystander cardiopulmonary resuscitation (CPR). Initial rhythm was shockable in 26.3% of patients and total CPR duration was 78 min [52–106]. Signs of life were noted for 31.3% of patients and a cardiac etiology precipitating event was present in 45.0%. Survival to discharge was 29.9%. Initial shockable rhythm was associated with increased odds of survival (unadjusted OR 4.7 [1.5–14.5]; p = 0.006), as were signs of life prior to ECMO (unadjusted OR 7.8 [2.6–23.4]; p < 0.001). Lactate levels early on-ECMO (unadjusted OR 0.89 [0.79–0.99]; p = 0.02) and at 24 h on-ECMO (unadjusted OR 0.62 [0.42–0.91]; p < 0.001) were associated with decreased odds of survival. ConclusionsThese preliminary data suggest that while overall survival is poor, a carefully selected pediatric OHCA patient may benefit from ECPR. Further studies are needed to understand long-term neurologic outcomes.

Abstract P429: Stronger Association of Angiotensinogen with Mortality than Renin or Lactate in Critical Illness

Introduction: Sepsis and septic shock remain global healthcare issues associated with high mortality rates affecting millions every year despite best care efforts. Activation of the renin-angiotensin-system (RAS) is an early event in sepsis, and renin levels may more strongly associate with mortality than serum lactate, a widely accepted index of patient status. We postulated that reduced levels of Angiotensinogen (AGT) may reflect a dysfunctional RAS driven by high renin levels but an attenuated expression of Ang II to adequately support tissue perfusion and blood pressure. This study compared the association with mortality of AGT to serum lactate and active renin in a subset of the VICTAS (Vitamin C, Thiamine, and Steroids in Sepsis) cohort (N=103) at baseline (day 0) prior to treatment. Methods: Serum levels of intact AGT and active renin protein were quantified by separate ELISAs. Biomarker discrimination for all-cause 30-day mortality was compared by receiver operating characteristic (ROC) curves generated by logistic regression models adjusted for age, sex, sequential organ failure assessment (SOFA) score, systolic blood pressure, and in-hospital vasopressor support. Association of serum AGT, renin, and lactate with mortality was assessed by Kaplan-Meier curves with log rank test and hazard ratios derived from Cox regression. Results: Median [interquartile range] serum levels for AGT were: 114 [78.2-205.4] nM; renin: 4.9 [2.2-13.6] pM; and lactate: 2.6 [1.7-3.8] mM. ROC curves revealed better discrimination of AGT for mortality than either active renin or lactate. The area under the curve (AUC) of AGT (0.82, 95% CI: 0.70, 0.93) was greater than lactate (AUC=0.68, 95% CI: 0.57, 0.80; p=0.022). Kaplan-Meier curves and log rank test also revealed that AGT levels below 114 nM associated with reduced survival. Renin levels greater than 4.9 pM were also associated with patient mortality albeit less than that for AGT while higher lactate levels (&gt;2.6 mM) were not associated with mortality in this cohort. Conclusion: AGT levels more strongly associated with 30-day mortality than renin or lactate in the VICTAS cohort. Reduced AGT may reflect increased consumption by high renin coupled with reduced expression by the liver ultimately impairing Ang II-AT 1 R tone in critically ill patients. The prospective assessment of circulating AGT may facilitate more precise therapeutic approaches treatment to restore a dysfunctional RAS and improve overall mortality in sepsis.

Mitochondrial dysfunction in platelets from severe trauma patients - A prospective case-control study

IntroductionTrauma-induced coagulopathy (TIC) refers to an abnormal coagulation process, an imbalance between coagulation and fibrinolysis due to several pathological factors, such as haemorrhage and tissue injury. Platelet activation and subsequent clot formation are associated with mitochondrial activity, suggesting a possible role for mitochondria in TIC. Comprehensive studies of mitochondrial dysfunction in platelets from severe trauma patients have not yet been performed. MethodsIn this prospective case-control study, patients with severe trauma (ISS≥16) had venous blood samples taken at arrival to the Emergency Unit of a Level 1 Trauma Centre. Mitochondrial functional measurements (Oxygraph-2k, Oroboros) were performed to determine oxygen consumption in different respiratory states, the H2O2 production and extramitochondrial Ca2+ movements. In addition, standard laboratory and coagulation tests, viscoelastometry (ClotPro) and aggregometry (Multiplate) were performed. Measurements data were compared with age and sex matched healthy control patients. ResultsSevere trauma patients (n = 113) with a median age of 38 years (IQR, 20–51), a median ISS of 28 (IQR, 20–48) met our inclusion criteria. Oxidative phosphorylation in platelet mitochondria from severe trauma patients significantly decreased compared to controls (34.7 ± 8.8 pmol/s/mL vs. 48.0 ± 19.7 pmol/s/mL). The mitochondrial H2O2 production significantly increased and greater endogenous Ca2+ release was found in the polytrauma group. Consistent with these results, clotting time (CT) increased while maximum clot firmness (MCF) decreased with the EX-test and FIB-test in severe trauma samples. Multiplate aggregometry showed significantly decreased ADP-test (38 ± 12 AUC vs. 112 ± 14 AUC) and ASPI test (78 ± 22 AUC vs. 84 ± 28 AUC) also tended to decrease in mitochondria of polytrauma patients as compared with controls. Significant strong correlation has been demonstrated between mitochondrial OxPhos and MCF while it was negatively correlated with ISS (R2=0.448, P˂0.05), INR, CT and lactate level of patients. ConclusionsThe present study revealed that severe trauma is associated with platelet mitochondrial dysfunction resulting in reduced ATP synthesis and impaired extramitochondrial Ca2+ movement. These factors are required for platelet activation, recruitment and clot stability likely thus, platelet mitochondrial dysfunction contributes to the development of TIC.