Elevated Lactate Levels Research Articles

Early Postoperative Serum Lactate Levels Predict Anastomotic Leakage After Minimally Invasive Esophagectomy.

Anastomotic leakage (AL) is a major complication after esophagectomy for esophageal cancer, and the significance of elevated postoperative lactate levels in the occurrence of AL is unclear. We evaluated 583 patients who underwent minimally invasive esophagectomy for esophageal cancer. Serum lactate levels were measured immediately after esophagectomy and in the morning on postoperative days (POD) 1, 2, 3, and 4. We also evaluated the factors associated with AL using multivariable logistic regression analysis. AL occurred in 8.9% (n = 52) of patients, and the median onset of AL was POD10 (interquartile range: 7-13). The lactate levels immediately after esophagectomy through POD3 were significantly higher in patients with AL than in those without AL. A further multivariable logistic regression analysis showed that elevated lactate level on POD2 was an independent predictor of the occurrence of AL (odds ratio 11.9; 95% confidence interval: 4.04-17.3; P < 0.001). Severe AL was significantly more frequent in the higher lactate patients (P < 0.001). Furthermore, in patients with AL with higher lactate, the onset tended to be earlier (P = 0.054), and the treatment duration of AL was significantly longer compared with those with lower lactate (P = 0.037). AL was significantly associated with elevated postoperative lactate levels. Elevated lactate levels on POD2 could be significant predictor of AL development after esophagectomy.

A cross-sectional study of point-of-care lactate testing in integrated community care management (ICCM) for children with acute respiratory illness in rural uganda.

Integrated community case management (iCCM) programs leverage lay village health workers (VHWs) to carry out the initial evaluation of children with common conditions including malaria, pneumonia and diarrhea. Therefore, it is imperative that VHWs are able to identify children who are critically ill and require referral to a health facility. Elevated venous lactate levels have been associated with severe illness and adverse health outcomes, including death. However, lactic acidosis may not be recognized in rural settings because it is not routinely measured outside of hospitals and research studies. Point-of-care lactate tests may help identify patients in need of a higher level of care and improve VHWs' ability to make timely and appropriate referrals. The study was a cross-sectional evaluation of children aged <5 y presenting to VHWs in rural southwestern Uganda with complaints of fever and cough. Demographics, clinical presentation, evaluation, management and disposition were recorded. VHWs were trained and instructed to perform lactate testing using a point-of-care assay in eligible participants. During the study period, 238 children were enrolled and completed an initial assessment. Of the 204 participants included in the analysis, 113 (55.4%) were female, and the median (IQR) age was 23 (9-36) months. Most participants, 139/200 (69.5%), had negative results on the malaria rapid diagnostic test. The median lactate level was 2.1mmol/L; 12% (24/204) had a lactate ≥3.5 mmol/L and only nine participants (4.4%) had a lactate ≥5mmol/L. Having a lactate level above either cut-off was not associated with the presence of danger signs at presentation. Few children presenting with fever and cough to VHWs in western Uganda had elevated lactate levels. However, most of the children with elevated lactate levels did not otherwise satisfy established iCCM criteria based on physical examination findings for referral to a health facility. Therefore, while elevated lactate was not associated with danger signs in this small study, it is possible that there is under-recognition of severe illness using current iCCM guidelines.

Early mNGS testing for diagnose and prognostic prediction of early onset pneumonia among in-hospital cardiac arrest patients undergoing extracorporeal cardiopulmonary resuscitation

ObjectivesMetagenomic next-generation sequencing (mNGS) is emerging as a novel diagnostic technology for various infectious diseases; however, limited studies have investigated its application in etiological diagnosis of early onset pneumonia (EOP) among patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital cardiac arrest (IHCA), The clinical significance of early mNGS in predicting short-term prognosis of IHCA patients after ECPR remains unclear.MethodsThis retrospective study included 76 patients with IHCA who underwent ECPR at the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022. Baseline characteristics and etiological data of all patients during their hospitalization were collected and statistically analyzed. The primary outcome of this study was the diagnosis of EOP, while the secondary outcomes included successful extracorporeal membrane oxygenation (ECMO) weaning and survival at discharge. Additionally, the characteristics of bronchoalveolar lavage fluid (BALF) flora in these patients were compared by analyzing both mNGS results and culture results.ResultsMultivariate logistic regression were employed to analyze the predictors of ECMO weaning failure, mortality at discharge, and the incidence of EOP. Ultimately, patients with lower SOFA scores on admission [OR (95%CI): 1.447 (1.107-1.890), p=0.007] and those who underwent early mNGS testing within 48 hours after ECPR [OR (95%CI): 0.273 (0.086-0.865), p=0.027] demonstrated a higher probability of successful weaning from ECMO. Patients with higher SOFA scores on admission [OR (95%CI): 2.404 (1.422-4.064), p=0.001], and elevated lactate levels [OR (95%CI): 1.176 (1.017-1.361), p=0.029] exhibited an increased likelihood of mortality at discharge. Furthermore, early mNGS detection [OR (95%CI): 0.186 (0.035-0.979), p=0.047], and lower CRP levels (48h-7d after ECMO) [OR (95%CI):1.011 (1.003-1.019), p=0.006] were associated with a reduced incidence of EOP. In addition, the pathogens detected by mNGS within 48 hours after ECPR were mainly oral colonizing bacteria and viruses, and viruses were in the majority, while all BALF cultures were negative. In contrast, between 48 hours and 7 days after ECPR, BALF cultures were positive in all EOP patients.ConclusionsEarly mNGS testing to identify microbial flora facilitates timely adjustment of antibiotic regimens, thereby reducing the incidence of EOP and improving short-term prognosis in patients undergoing ECPR following IHCA.

ACEF score and lactate: lifeline predictors in endocarditis valve procedures: insights from a single-center study.

This study aimed to assess the prognostic value of routinely collected laboratory parameters, specifically lactate, troponin-T, and CK-MB, in predicting mortality in patients with surgically treated endocarditis. Additionally, the study evaluated the effectiveness of two mortality scores, EuroSCORE II and ACEF II Score, in this clinical context. We retrospectively analyzed data from 130 patients diagnosed with endocarditis who underwent surgery at a single tertiary center over nine years. The study utilized preoperative mortality scores and laboratory parameters collected within the first 24h post-surgery. Statistical analyses included AUROC curves, Kaplan-Meier survival analyses, and correlation analyses to determine predictive values and associations with patient outcomes. Among the 130 patients, 28 (21.5%) died within one year post-surgery. Elevated postoperative lactate levels were significantly associated with increased short- and long-term mortality, with AUROC values indicating strong predictive capability. The ACEF II Score also demonstrated significant predictive value for mortality at various time points, outperforming EuroSCORE II. Higher lactate levels and ACEF II Scores correlated with increased hazard ratios for mortality. Kaplan-Meier analyses revealed significant survival differences based on lactate and ACEF II Score thresholds. Postoperative lactate levels and the ACEF II Score are robust predictors of mortality in patients undergoing cardiac surgery for endocarditis. Integrating these parameters into clinical practice can enhance risk stratification and guide therapeutic decisions, improving patient outcomes through personalized care. Further studies are needed to validate these findings across diverse populations and explore additional biomarkers for refined predictive accuracy.

Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway

As a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1α activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1α signaling. Mice given HIF-1α inhibitor PTX-478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1α pathway, suggesting potential new targets for combating the virus.

Glycolytic activity following anti-CD19 CAR-T cell infusion in non-Hodgkin lymphoma.

Energy metabolism of chimeric antigen receptor-T cells (CAR-T) activation in humans remains unexplored. As a glycolytic activity surrogate, we investigated the dynamics of peripheral blood (PB) lactate in the first weeks post-CAR-T infusion. In 17 patients treated with CD28 harbording anti-CD19 CAR-T for relapsed/refractory non-Hodgkin lymphomas, PB lactate levels increased following CAR-T infusion. Elevated lactate levels correlated with longer CAR-T persistence and higher CD8+/CD4+ ratio. Peripheral blood lactate kinetics may reflect immune cells activation and be useful for bedside monitoring.

Scalable enzymatic lactate sensor for continuous monitoring in interstitial fluid

Abstract Elevated lactate levels have been shown to be an indicator of poor outcome in cardiovascular patients [1]. Moreover, continuous monitoring of lactate may be more clinically valuable than the absolute value of lactate for risk stratification [2]. A promising approach involves the implementation of a lactate monitoring system inspired by advanced continuous glucose monitoring [3] to provide real-time measurements of lactate in interstitial fluid (ISF) based on miniaturized lactate sensors with submillimeter dimensions. The proposed amperometric lactate sensor employs Pt electrodes (WE = 0.785 mm²) on which the enzyme lactate oxidase is immobilized to selectively detect lactate. The sensing mechanism, shown in Fig. 1a, is based on the conversion of lactate to hydrogen peroxide, which then undergoes oxidation at the electrode surface, generating a current proportional to the concentration of lactate. Amperometric measurements are performed with an applied potential of 0.5 V, a sample volume of 2 µL and a flow rate of 1 µL/min, respecting real-life conditions. The response of the sensor towards lactate is shown in Fig. 1c, demonstrating excellent reversibility, long-term stability over 8 hours and negligible cross sensitivity to glucose (G), ascorbic acid (AA) and uric acid (UA). In addition, the sensor linear range can be extended by 10x by incorporating an outer Nafion layer, acting as a diffusion-limiter. As shown in Fig. 1d, by adjusting the thickness of Nafion layer, the linear range increases up to 20 mM lactate, as per ICU specifications. The physiological challenges associated with ISF extraction prompted us to develop a minimally invasive, submillimeter-sized sensor for direct placement inside the body. To address the most critical step of miniaturization, we have successfully fabricated a three-electrode platform on a Si ribbon measuring 300x1500 µm² and a thickness of 100 µm (Fig. 2a). The sensor is also drastically scaled down, with smallest design having a total sensing area of 200x500 µm² (WE = 0.026 mm², Fig. 2b). Its response to lactate is displayed in Fig. 2c, confirming a reliable functionality. Fig. 2d presents the calibration curves obtained from sensors with different sizes, indicating that the reduction in size does not affect the sensitivity. The developed lactate sensor demonstrates excellent performance: high sensitivity, excellent reversibility, and high stability. In addition, the linear range of the sensor is tunable by integrating an outer Nafion membrane. Finally, we demonstrate the successful fabrication and characterization of submillimeter-sized sensors, opening up their potential for minimally invasive in-vivo measurements.Working principle and characterizationCharacterization miniaturized sensors

Patient characteristics and clinical outcome in acute myocardial infarction related cardiogenic shock according to vascular access site for PCI

Abstract Background / Introduction The optimal vascular access site for percutaneous coronary interventions (PCI) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains uncertain. While observational data favor trans-radial access (TRA) due to lower complication rates and mortality, trans-femoral (TFA) PCI offers advantages such as shorter access and procedure times, along with quicker escalation to mechanical circulatory support (MCS). Purpose In this study, we aimed to investigate factors associated with a transfemoral approach and compare mortality rates between TRA and TFA in AMI-CS patients undergoing PCI. Methods Data from a nationwide registry of AMI-CS patients undergoing PCI (2017-2021) were analyzed. We compared patient demographics, procedural details, and outcomes between TRA and TFA groups. Logistic regression identified access site factors and radial-to-femoral cross-over predictors. Propensity score matched (PSM) analysis examined the impact of access site on mortality. Results Of 1562 patients, 45% underwent TRA PCI, with an increasing trend over time. TFA patients were more often female, had a history of coronary artery bypass grafting (CABG), lower blood pressure, higher resuscitation and intubation rates, and elevated lactate levels. After PSM, 30-day mortality was lower in TRA (33% vs. 46%, p &amp;lt;0.001). Predictors for cross-over included left coronary artery interventions, multivessel PCI, and MCS initiation. Conclusion Significant differences exist between TRA and TFA PCI in AMI-CS. TFA was more common in patients with worse hemodynamics and was associated with higher 30-day mortality compared to TRA. TRA should be the default access, given its feasibility and favorable outcomes in many patients.Baseline characteristicsPredictors for femoral access

Classification of 90-day mortality risk among patients with cardiogenic shock requiring advanced mechanical circulatory support

Abstract Background The SCAI shock classification aims to provide a simple and practical stratification of the severity of patients with cardiogenic shock (CS) and to immediately offer them crucial treatments such as mechanical circulatory support (MCS). Additionally, the IABP shock II risk score is designed to predict 30-day mortality in patients with CS following acute coronary syndrome (ACS), and the SAVE score can also predict in-hospital mortality for patients after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) insertion due to refractory CS. However, previous studies on SCAI staging in patients with MCS have been inconsistent, and the association with prognosis remains unclear. Purpose The aim of this study is to investigate the correlation between the SCAI shock stage and prognosis in ACS patients requiring advanced MCS, and to compare it with other prognostic scores. Methods From January 2012 to July 2023, 137 ACS patients with advanced MCS (excluding IABP) were evaluated. Upon ICU admission, patients were categorized into SCAI stages B to E. The IABP shock II score and the SAVE score were also calculated to serve as prognostic tools. The type of MCS was categorized as Impella, VA-ECMO with IABP, and ECPELLA (VA-ECMO with Impella). We compared the 90-day survival rates with the SCAI shock stage and other prognostic tools. Result The distribution for SCAI classifications stage B to E was 13 (10%), 38 (28%), 21 (15%), and 65 (47%), respectively. There were no significant differences among the groups regarding age, gender, comorbidities, the ratio of ST-elevation myocardial infarction, door-to-balloon time, and onset-to-reperfusion time. In SCAI Stage E, a significantly higher proportion of patients (86%) underwent extracorporeal cardiopulmonary resuscitation, exhibiting elevated lactate and peak CK-MB levels, along with higher IABP Shock II and lower SAVE scores, compared to other stages. A Kaplan-Meier analysis of 90-day mortality, based on the SCAI, the IABP Shock II, the SAVE categories, and the type of MCS, demonstrated that outcomes deteriorated as the stage advanced across all classifications. In the univariate Cox regression analysis for 90-day mortality, significant differences in outcomes were observed across the four classifications. However, in the multivariate Cox regression analysis that incorporated all four classifications, only the type of MCS (Impella vs. ECMO with IABP; hazard ratio [HR] 0.36; 95% confidence interval [CI], 0.16 - 0.78, p = 0.012) and the SCAI classification (stage E vs. stage C; HR 3.03; 95% CI, 1.51 - 6.08, p = 0.002) demonstrated a significant association with 90-day mortality. Conclusion The SCAI shock stage upon ICU admission suggests the potential for convenient prediction of mid-term outcomes in ACS patients who received advanced MCS.

Effect of glucose-insulin-potassium on lactate levels at the end of surgery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a randomized controlled trial

IntroductionCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications.Methods and analysisThe modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization.Ethics and disseminationThe trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals.Trial registrationChiCTR2200057258. Registered on March 5, 2022.

Establishment and Verification of a Novel Gene Signature Connecting Hypoxia and Lactylation for Predicting Prognosis and Immunotherapy of Pancreatic Ductal Adenocarcinoma Patients by Integrating Multi-Machine Learning and Single-Cell Analysis.

Pancreatic ductal adenocarcinoma (PDAC) has earned a notorious reputation as one of the most formidable and deadliest malignant tumors. Within the tumor microenvironment, cancer cells have acquired the capability to maintain incessant expansion and increased proliferation in response to hypoxia via metabolic reconfiguration, leading to elevated levels of lactate within the tumor surroundings. However, there have been limited studies specifically investigating the association between hypoxia and lactic acid metabolism-related lactylation in PDAC. In this study, multiple machine learning approaches, including LASSO regression analysis, XGBoost, and Random Forest, were employed to identify hub genes and construct a prognostic risk signature. The implementation of the CERES score and single-cell analysis was used to discern a prospective therapeutic target for the management of PDAC. CCK8 assay, colony formation assays, transwell, and wound-healing assays were used to explore both the proliferation and migration of PDAC cells affected by CENPA. In conclusion, we discovered two distinct subtypes characterized by their unique hypoxia and lactylation profiles and developed a risk score to evaluate prognosis, as well as response to immunotherapy and chemotherapy, in PDAC patients. Furthermore, we indicated that CENPA may serve as a promising therapeutic target for PDAC.

Correlation of Serum Lactate and Shock Index as Mortality Predictor in Polytrauma Patients

In polytrauma patients, serum lactate and hypovolemic shock are critical biomarkers for prognosis and treatment guidance. Elevated lactate levels indicate tissue hypoperfusion and anaerobic metabolism, often correlating with increased mortality. Objective: To analyze the correlation between serum lactate levels and shock index as predictors of in-hospital mortality in polytrauma patients. Methods: A Cohort study was conducted from August 2022 to July 2023 at a single tertiary care hospital in Karachi. Patients were chosen via consecutive sampling techniques and included adult patients with polytrauma injuries (ISS ≥ 15) who survived at least 24 hours. Patients with a history of diabetes were excluded. The serum lactate levels and shock index at the time of admission and over the first 24 hours were the exposures while in-hospital mortality, was the primary outcome. Statistical analyses were conducted using Stata 16.0. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression evaluated mortality risk, adjusting for age, ISS, and shock index. Results: The in-hospital mortality rate in the study was 6.4% with significant predictors of mortality included increasing age (47.05 vs. 27.62 years, p&lt;0.001), higher Injury Severity Scores (ISS) (24 vs. 19, p= 0.02), and elevated shock index at admission (0.84 vs. 0.71, p&lt;0.001). Lactate metrics were strongly associated with mortality, showing significant correlations. Conclusions: Higher serum lactate levels and shock index are strong predictors of mortality in polytrauma patients. Greater age and injury severity also contribute to poorer outcomes.

CNDP2: An Enzyme Linking Metabolism and Cardiovascular Diseases?

The heart requires a substantial amount of energy to function, utilising various substrates including lipids, glucose and lactate as energy sources. In times of increased stress, lactate becomes the primary energy source of the heart, but persistently elevated lactate levels are linked to poor patient outcomes and increased mortality. Recently, carnosine dipeptidase II (CNDP2) was discovered to catalyse the formation of Lac-Phe, an exercise-induced metabolite derived from lactate, which has been shown to suppress appetite in mice and reduce adipose tissue in humans. This review discusses CNDP2, including its role in lactate clearance, carnosine hydrolysis, oxidative stress regulation, and involvement in metabolite regulation. The association between CNDP2 and cardiometabolic and renal diseases is also explored, and knowledge gaps are highlighted. CNDP2 appears to be a complex participant in human physiological processes and disease, necessitating additional research to unveil its functions and potential therapeutic applications.

LDHB-deficient brain exhibits resistance to ischemic neuronal cell death due to increased vasodilation

Ischemic stroke triggers a cascade of metabolic and inflammatory events leading to neuronal death, particularly in the hippocampus. Here, we investigate the role of lactate metabolism in ischemic resistance using LDHB-deficient mice, which exhibit impaired lactate utilization. Contrary to expectations of severe neuronal damage due to metabolic defects, LDHB-deficient mice displayed significantly increased neuronal survival following ischemic insult. Magnetic resonance spectroscopy revealed elevated lactate levels in LDHB-deficient brains, which correlated with enhanced vasodilation of the posterior communicating artery (PComA) and increased extracellular PGE2 levels. These findings suggest that elevated lactate inhibits PGE2 reabsorption, promoting vasodilation and neuronal protection. Our results highlight lactate's potential role in neuroprotection and its therapeutic promise for ischemic stroke.

Cerebrospinal Fluid Lactate Levels as a Prognostic Indicator in Patients With Cryptococcal Meningitis Who Are HIV Negative: A Retrospective Cohort Study.

Cryptococcal meningitis (CM) is a severe central nervous system infection. In patients with HIV infections and coexisting CM, elevated baseline cerebrospinal fluid (CSF) lactate levels can predict increased mortality. However, the CSF lactate level's significance in patients with CM who are HIV negative remains unclear, necessitating further investigation to elucidate the potential distinctions and enhance patient management. This study investigated the significance of CSF lactate levels in patients with CM who were HIV negative. This retrospective study utilized data from the clinical databases of patients who underwent lumbar punctures at a medical center in Kaohsiung City, southern Taiwan. Demographic data, CSF lactate levels, routine CSF analyses, and hematologic and neurologic findings were evaluated. The optimal CSF lactate threshold value was determined by the Youden index. This retrospective study included 70 patients with CM, among whom 44 (63%) and 26 (37%) tested negative and positive for HIV, respectively. The group without HIV exhibited higher CSF lactate levels, with an optimal CSF lactate cutoff point of 7.935 mmol/L for predicting 90-day mortality, resulting in significant predictive accuracies (area under the curve, 0.755; sensitivity, 57.1%; specificity, 100%); this value was an independent mortality predictor in patients who were HIV negative. In patients with CM who were HIV negative, CSF lactate levels ≥7.935 mmol/L correlated with higher mortality rates but without statistical significance. All patients with CM who were HIV negative and had CSF lactate levels ≥7.935 mmol/L died within 3 months of admission. Patients with CM who were HIV negative had elevated CSF lactate levels that correlated with adverse outcomes, enabling early identification of high-risk individuals.

A Rapid Increase in Serum Lactate Levels after Cardiovascular Surgery Is Associated with Postoperative Serious Adverse Events: A Single Center Retrospective Study.

Hyperlactatemia is a common predictive factor for poor post-cardiovascular surgery outcomes. However, it is not well understood whether the rapid postoperative lactate level elevation in a short period of time is associated with patient outcomes. Herein, we investigated the relationship between the degree of change in serum lactate levels and postoperative serious adverse events (PSAEs), including mortality, within 24 h of cardiovascular surgery. In this retrospective study, we evaluated the relationship between a rapid serum lactate level increase and PSAEs after open-heart and major vascular surgery. We divided the patients into those with and without PSAEs. Univariate and multivariate analyses were performed to evaluate the association between PSAEs and rapid lactate level increases. We enrolled 445 patients; 16% (n = 71) had PSAEs. The peak lactate levels during the first 24 h of intensive care unit (ICU) stay were higher in patients with PSAEs than in those without. The maximum change in lactate levels between two consecutive lactate measurements during the first 24 h after ICU admission was higher in patients with PSAEs than in those without. A multivariate logistic regression analysis revealed that changes in lactate levels of 2 mmol/L or more between two consecutive lactate measurements were associated with PSAEs. ICU peak lactate levels of 3 mmol/L or more were not associated with PSAEs. Rapid serum lactate level increases of 2 mmol/L or more during the first 24 h of ICU admission post-cardiovascular surgery are associated with PSAEs.

β-Adrenergic Agonist-Induced Lactic Acidosis: A Case Report.

β-Adrenergic agonist medications such as albuterol are the mainstay for treatment of patients with acute asthma exacerbations. Patients who present to the emergency department with severe symptoms are often treated with multiple albuterol doses in sequence to maximize the impact of the medications, relax bronchoconstriction, and relieve their breathlessness. Patients who present with acute dyspnea have numerous potential causes of hyperlactatemia and acidosis including an uncommonly recognized outcome of albuterol administration. This clinical case report outlines a scenario where a patient who was treated for an acute asthma exacerbation had rising lactate levels despite improving clinically. Causes of elevated lactate levels are discussed, particularly related to β-adrenergic agonist use, and considerations for monitoring and withdrawal of albuterol administration are outlined.

Prognostic Significance of Lactate Clearance in Cardiogenic Pulmonary Edema in the Emergency Department.

Background and Objectives: Acute cardiorespiratory failure disrupts the delicate balance of energy supply, demand, and consumption, with elevated lactate levels and decreased blood pH serving as crucial indicators. Acute cardiogenic pulmonary edema (ACPO), a common cause of acute respiratory failure, poses a substantial mortality risk. Lactate, a byproduct of pyruvate reduction, is a pertinent marker in perfusion assessment. Lactate clearance (LC) has proven prognostic efficacy in various conditions but lacks consensus on its predictive power in acute cardiogenic pulmonary edema. Materials and Methods: This prospective observational study, conducted in a metropolitan area's third-level emergency department, involved patients with cardiogenic pulmonary edema from May 2021 to August 2023. The inclusion criteria specified acute cardiogenic pulmonary edema, excluding patients with incomplete data or other respiratory conditions. Lactate clearance, calculated at presentation and after 6 h, served as the primary outcome predictor. Our data analysis employed logistic regression, the ROC curve, and statistical tests. Results: The cohort of 106 patients revealed that a lactate clearance below 14.29% was significantly associated with mortality. While 51.6% of survivors were discharged, LC's predictive success for discharge was inconclusive. Logistic regression underscored the significance of lactate clearance, with a one-unit increase yielding a 5.55-fold probability of survival. The AUC for LC was 0.759. Conclusions: This study pioneers the exploration of lactate clearance in patients with acute cardiogenic pulmonary edema. LC below 14.29% signifies a poor prognosis, emphasizing its potential as an early treatment initiation marker. While acknowledging this study's limitations, we advocate for further multicenter research to refine the understanding of lactate clearance in this context.

Lactate supports Treg function and immune balance via MGAT1 effects on N-glycosylation in the mitochondria.

Current research reports that lactate affects Treg metabolism, although the precise mechanism has only been partially elucidated. In this study, we presented evidence demonstrating that elevated lactate levels enhanced cell proliferation, suppressive capabilities, and oxidative phosphorylation (OXPHOS) in human Tregs. The expression levels of Monocarboxylate Transporters 1/2/4 (MCT1/2/4) regulate intracellular lactate concentration, thereby influencing the varying responses observed in naive Tregs and memory Tregs. Through mitochondrial isolation, sequencing, and analysis of human Tregs, we determined that α-1,3-Mannosyl-Glycoprotein 2-β-N-Acetylglucosaminyltransferase (MGAT1) served as the pivotal driver initiating downstream N-glycosylation events involving progranulin (GRN) and hypoxia-upregulated 1 (HYOU1), consequently enhancing Treg OXPHOS. The mechanism by which MGAT1 was upregulated in mitochondria depended on elevated intracellular lactate that promoted the activation of XBP1s. This, in turn, supported MGAT1 transcription as well as the interaction of lactate with the translocase of the mitochondrial outer membrane 70 (TOM70) import receptor, facilitating MGAT1 translocation into mitochondria. Pretreatment of Tregs with lactate reduced mortality in a xenogeneic graft-versus-host disease (GvHD) model. Together, these findings underscored the active regulatory role of lactate in human Treg metabolism through the upregulation of MGAT1 transcription and its facilitated translocation into the mitochondria.

Pluronic F127-Complexed PEGylated Poly(glutamic acid)-Cisplatin Nanomedicine for Enhanced Glioblastoma Therapy.

Glioblastoma is one of the most aggressive and treatment-resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127-complexed PEGylated poly(glutamic acid)-cisplatin (PLG-PEG/PF127-CDDP). PLG-PEG/PF127-CDDP demonstrated an optimal size of 133.97±12.60nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half-maximal (50%) inhibitory concentration (IC50) of 12.61µgmL-1 at 48h and a 72.53%±1.89% reduction in cell invasion. Furthermore, PLG-PEG/PF127-CDDP prolonged the circulation half-life of cisplatin to 9.75h in vivo, leading to a more than 50% reduction in tumor size on day 16 post-treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG-PEG/PF127-CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer-based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications.