Elevated Lactate Levels Research Articles

Elevated venous lactate level as an early predictive marker of organ failure in acute pancreatitis: a retrospective study.

The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.

Initial lactate levels linked to oliguria in term neonates with perinatal asphyxia

BackgroundOliguria is a sign of impaired kidney function and has been shown to be an early predictor of adverse prognoses in patients with acute kidney injury. The relationship between urine output (UOP) and early lactate levels in neonates with perinatal asphyxia (PA) has not been extensively explored. This study aimed to investigate the link between oliguria during the first 24 h of life and early lactate levels in neonates with PA.MethodsThe medical records of 293 term neonates with asphyxia from 9216 hospitalized newborns were retrospectively analyzed, including 127 cases designated as the oliguria group and 166 cases as controls. Peripheral arterial blood gas after PA and UOP within 24 h after birth were analyzed. Logistic regression analyses and receiver operating characteristic curve analysis were conducted.ResultsOliguria occurred in 43.34% of neonates with PA. The median UOP of the oliguria and control groups were 0.65 and 1.46 mL/kg/h, respectively. Elevated lactate levels after PA are an independent risk factor for oliguria in the following 24 h (p = 0.01; OR: 1.19; 95%CI: 1.04–1.35) and show a moderate discriminatory power for oliguria (AUC = 0.62). Using a cut off value of 8.15 mmol/L, the positive and negative predictive values and the specificity were 59.34%, 63.86%, and 78.30%, respectively.ConclusionNeonates with elevated lactate levels after PA face a risk of oliguria in the following 24 h. Based on early elevated lactate levels after resuscitation, especially ≥ 8.15 mmol/L, meticulously monitoring UOP will allow this vulnerable population to receive early, tailored fluid management and medical intervention.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Inhibition of Pyruvate Dehydrogenase Kinase 4 Protects Cardiomyocytes from lipopolysaccharide-Induced Mitochondrial Damage by Reducing Lactate Accumulation.

Mitochondrial dysfunction is considered one of the major pathogenic mechanisms of sepsis-induced cardiomyopathy (SIC). Pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of mitochondrial metabolism, is essential for maintaining mitochondrial function. However, its specific role in SIC remains unclear. To investigate this, we established an in vitro model of septic cardiomyopathy using lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Our study revealed a significant increase in PDK4 expression in LPS-treated H9C2 cardiomyocytes. Inhibiting PDK4 with dichloroacetic acid (DCA) improved cell survival, reduced intracellular lipid accumulation and calcium overload, and restored mitochondrial structure and respiratory capacity while decreasing lactate accumulation. Similarly, Oxamate, a lactate dehydrogenase inhibitor, exhibited similar effects to DCA in LPS-treated H9C2 cardiomyocytes. To further validate whether PDK4 causes cardiomyocyte and mitochondrial damage in SIC by promoting lactate production, we upregulated PDK4 expression using PDK4-overexpressing lentivirus in H9C2 cardiomyocytes. This resulted in elevated lactate levels, impaired mitochondrial structure, and reduced mitochondrial respiratory capacity. However, inhibiting lactate production reversed the mitochondrial dysfunction caused by PDK4 upregulation. In conclusion, our study highlights the pathogenic role of PDK4 in LPS-induced cardiomyocyte and mitochondrial damage by promoting lactate production. Therefore, targeting PDK4 and its downstream product lactate may serve as promising therapeutic approaches for treating SIC.

A comparison between the enzymatic oxidation method and headspace gas chromatography with a flame ionization detector in the determination of postmortem blood ethanol.

Ethanol is the most commonly encountered substance in forensic toxicology. Determining blood alcohol concentration (BAC) in autopsies accounts for the majority of work in forensic diagnosis. The most common method to assess BAC is the enzymatic oxidation method because of its low cost, easy operation, and high throughput. Still, the elevated lactate and lactate dehydrogenase (LDH) levels in postmortem blood may affect accuracy. This study uses headspace gas chromatography with a flame ionization detector (HS-GC/FID) to assess the interference of lactate and LDH levels on BAC in 110 autopsied blood samples determined by the enzymatic oxidation method. The results showed that lactate and LDH levels in postmortem blood were higher than in normal blood. There was a weak correlation between the lactate levels and BAC difference (r = 0.23, p < 0.05) and a strong correlation between LDH levels and BAC difference (r = 0.67, p < 0.001). The differentiation of BAC between the enzymatic oxidation method and HS-GC/FID was significant (p < 0.001), confirming the interference significantly. All postmortem blood samples with lactate and LDH levels higher than regular lead to a positive error in determining BAC by enzymatic oxidation method. The study results suggest that the HS-GC/FID method should be used to determine BAC in postmortem blood samples instead of the enzymatic oxidation method to avoid mistakes in forensic diagnosis.

Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review

BackgroundPontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH.MethodsCases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH.ResultsThis study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9.ConclusionsThis study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH.

A comprehensive multiplatform metabolomic analysis reveals alterations of 2-hydroxybutyric acid among women with deep endometriosis related to the pesticide trans-nonachlor

BackgroundExposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. MethodologyA hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance (1H NMR) to cover polar and non-polar fractions. A “meet-in-the-middle” statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. ResultsFourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. ConclusionsTo the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms.

Pseudomonas Aeruginosa Affects the Function of Pulmonary Vascular Endothelial Cells

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.

Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined usingreal-time quantitative polymerase chain reaction,while EV species were identified by5'UTR region sequencing.Median viral load was 5.72 log10 copies/mL and did not differ by subjects'age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Metformin Attenuates Neutrophil Recruitment through the H3K18 Lactylation/Reactive Oxygen Species Pathway in Zebrafish.

Beyond its well-established role in diabetes management, metformin has gained attention as a promising therapeutic for inflammation-related diseases, largely due to its antioxidant capabilities. However, the mechanistic underpinnings of this effect remain elusive. Using in vivo zebrafish models of inflammation, we explored the impact of metformin on neutrophil recruitment and the underlying mechanisms involved. Our data indicate that metformin reduces histone (H3K18) lactylation, leading to the decreased production of reactive oxygen species (ROS) and a muted neutrophil response to both caudal fin injury and otic vesicle inflammation. To investigate the precise mechanisms through which metformin modulates neutrophil migration via ROS and H3K18 lactylation, we meticulously established the correlation between metformin-induced suppression of H3K18 lactylation and ROS levels. Through supplementary experiments involving the restoration of lactate and ROS, our findings demonstrated that elevated levels of both lactate and ROS significantly promoted the inflammatory response in zebrafish. Collectively, our study illuminates previously unexplored avenues of metformin's antioxidant and anti-inflammatory actions through the downregulation of H3K18 lactylation and ROS production, highlighting the crucial role of epigenetic regulation in inflammation and pointing to metformin's potential in treating inflammation-associated conditions.

The Role of Lactate Level as Predictor of Mortality Critically Ill Children at Moewardi Hospital

Background: The prevalence of mortality among critically ill children worldwide, particularly in Indonesia, remains alarmingly high. Numerous studies have indicated that elevated lactate levels serve as a significant predictor of mortality in this vulnerable population. The primary objective of this study is to elucidate the predictive value of lactate levels in determining mortality risk among critically ill children. Subjects and Method: A cohort prospective study was conducted in children aged between 1 month and 18 years old who met the criteria for critically ill children treated in the Pediatric High care unit (PHCU) of Dr. Moewardi General Hospital, Surakarta from January to June 2023. The dependent variable was the mortality. The independent variable was lactate level serum. The data were collected using questionnaire and observation sheet. The cut off point of lactate level was determined with ROC curve. Results: Among thirty critically ill pediatric patients, 43.3% died, while 56.7% survived. The deceased predominantly comprised females, with a mean age of 5.62 years (SD= 4.14). The mean lactate levels of those who died in the first hour, 6 hours, and 24 hours (Mean= 2.94; SD= 0.90) with a cut-off value of ≥2.35 mmol/L, (Mean= 3.20; SD= 0.50) with a cut-off value of ≥ 2.35 mmol/L and (Mean= 3.65; SD= 0.53) with a cut-off value of ≥2.95 mmol/L, respectively. The 24th hours lactate levels (persistence hyperlactatemia) had the highest sensitivity (92.3%) and specificity (100%) for predicting mortality (p&lt;0.001). Conclusion: In critically ill children, lactate level of ≥2.95 mmol/L is a good predictor of mortality. Keywords: lactate level, mortality, critically ill children. Correspondence: Reza Ervanda Zilmi. Department of Pediatrics, Sebelas Maret University/Dr. Moewardi General Hospital, Surakarta, Central Java, Indonesia. Kolonel Sutarto Street No. 132, Surakarta, Indonesia. email: zilmiervanda@gmail.com Phone: 081258038925.

Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis

BackgroundCisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. MethodsLactate levels were measured by lactate detection kit. Cisplatin-resistance NSCLC cells were established using progressive concentration of cisplatin. Cell viability, proliferation, and apoptosis were detected by CCK-8, EdU, and flow cytometry, respectively. Cell proliferation in vivo was determined by immunohistochemistry of Ki67 and apoptotic cells were calculated by the TUNEL. MeRIP-PCR was used to measure FOXO3 m6A levels. The interactions of genes were analyzed via RIP, ChIP, Dual-luciferase reporter, and RNA pull-down, respectively. ResultsElevated lactate levels were observed in both NSCLC patients and cisplatin-resistance cells. Lactate treatment increased cisplatin-resistance cell viability in vitro and promoted tumor growth in vivo. Mechanistically, lactate downregulated FOXO3 by YTHDF2-mediated m6A modification. FOXO3 transcriptionally reduced MAGI1-IT1 expression. FOXO3 overexpression inhibited the lactate-induced promotion of cisplatin resistance in NSCLC, which were reversed by MAGI1-IT1 overexpression. MAGI1-IT1 and IL6R competitively bound miR-664b-3p. FOXO3 overexpression or MAGI1-IT1 knockdown repressed lactate-mediated cisplatin resistance in vivo. ConclusionLactate promoted NSCLC cisplatin resistance through regulating FOXO3/MAGI1-IT1/miR-664b-3p/IL6R axis in YTHDF2-mediated m6A modification.

Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.

We present a male patient carrying a pathogenic MECP2 p. Arg179Trp variant with predominant negative psychiatric features and multilevel evidence of mitochondrial dysfunction who responded to the cariprazine treatment. He had delayed speech development and later experienced severe social anxiety, learning disabilities, cognitive slowing, and predominant negative psychiatric symptoms associated with rigidity. Clinical examinations showed multisystemic involvement. Together with elevated ergometric lactate levels, the clinical picture suggested mitochondrial disease, which was also supported by muscle histopathology. Exploratory transcriptome analysis also revealed the involvement of metabolic and oxidative phosphorylation pathways. Whole-exome sequencing identified a pathogenic MECP2 variant, which can explain both the dopamine imbalance and mitochondrial dysfunction in this patient. Mitochondrial dysfunction was previously suggested in classical Rett syndrome, and we detected related phenotype evidence on multiple consistent levels for the first time in a MECP2 variant carrier male. This study further supports the importance of the MECP2 gene in the mitochondrial pathways, which can open the gate for more personalized therapeutic interventions. Good cariprazine response highlights the role of dopamine dysfunction in the complex psychiatric symptoms of Rett syndrome. This can help identify the optimal treatment strategy from a transdiagnostic perspective instead of a classical diagnostic category.

Validating the performance of organ dysfunction scores in children with infection: A cohort study.

We aimed to validate the performance of six available scoring models for predicting hospital mortality in children with suspected or confirmed infections. This single-center retrospective cohort study included pediatric patients admitted to the PICU for infection. The primary outcome was hospital mortality. The six scores included the age-adapted pSOFA score, SIRS score, PELOD2 score, Sepsis-2 score, qSOFA score, and PMODS. Of the 5,356 children admitted to the PICU, 9.1% (488) died, and 25.1% (1,342) had basic disease with a mortality rate of 12.7% (171); 65.3% (3,499) of the patients were younger than 2 years, and 59.4% (3,183) were male. The discrimination abilities of the pSOFA and PELOD2 scores were superior to those of the other models. The calibration curves of the pSOFA and PELOD2 scores were consistent between the predictions and observations. Elevated lactate levels were a risk factor for mortality. The pSOFA and PELOD2 scores had superior predictive performance for mortality. Given the relative unavailability of items and clinical operability, the pSOFA score should be recommended as an optimal tool for acute organ dysfunction in pediatric sepsis patients. Elevated lactate levels are related to a greater risk of death from infection in children in the PICU.

Leigh syndrome: a must-know bilateral symmetrical basal ganglia affection

Leigh's syndrome also known as subacute necrotizing encephalomyopathy is a rare progressive neurological disease with a reserved prognosis affecting the brainstem and the basal nuclei, the symptomatology of which is revealed in the majority of cases during the first two years of life. In this article we report the case of an 4 years old child referred to our center following a consultation for delayed psychomotor acquisitions with axial hypotonia and elevated lactate levels. Brain MRI showed a characteristic appearance of this syndrome. This clinical case reports the MRI aspect of Leigh's syndrome, a rare and serious pathology responsible for bilateral and symmetrical lesions of the basal ganglia.

Effect of One Session of Muscle Blood Flow Restriction Training Versus Normal Training on Blood Lactate Level.

Blood flow restriction training (BFRT) is useful for improving muscle strength. However, it involves a long training time and is unsuitable for vigorous exercise. Muscle blood flow restriction training (MBFRT), which uses multiple parallel pneumatic cuffs (MPCs) to compress large areas of the extremities and restrict blood flow, was subsequently developed to address these issues. This study compared the effects of MBFRT with normal training (NT). Ten healthy adults underwent low-intensity MBFRT. MPC pressure was increased to 200 mmHg just before training. The exercise was a bodyweight half-squat. Three sets of 30 squats were performed. Two weeks later, the participants underwent NT with the same exercise. Blood lactate levels were measured before the start of training and at 1 and 5 min after training. The Borg index was also measured at the end of the training. The blood lactate level was elevated at 1 min after MBFRT and NT. The elevated blood lactate level was maintained at 5 min after MBFRT, whereas the lactate level was significantly decreased at 5 min after NT. The Borg index at the end of the training was significantly higher in MBFRT than in NT. Lactic acid accumulates in the muscles during low-intensity MBFRT, thereby initiating type II fiber activity.

Case 321: Leigh Syndrome.

A 9-month-old preterm male infant born at 33 weeks gestation presented with a 2-month history of developmental decline. The parents reported that over the past several months, they noted regression of milestones, where the infant stopped smiling, crying, expressing himself, or making eye contact. The parents also reported that the infant had multiple seizures during which he would wake up stiff and stare into space for 10-20 seconds while his lips would become blue. The parents were referred to a neurologist, where physical examination was notable for hypotonia. Electroencephalography (EEG) revealed frequent bilateral parietal epileptiform discharges. The patient was subsequently started on lacosamide. The patient's medical history was notable for abnormally low citrulline levels at birth, with negative results of urea cycle disorder testing at the time, along with left inguinal hernia repair performed 3 months ago. More recent laboratory analysis had shown persistently elevated serum lactate and alanine levels. There was no history of travel, recent infection, or vaccine administration. MRI of the brain with spectroscopy was performed for further evaluation.

Distinct lactate metabolism between hepatocytes and myotubes revealed by live cell imaging with genetically encoded indicators

The process of glycolysis breaks down glycogen stored in muscles, producing lactate through pyruvate to generate energy. Excess lactate is then released into the bloodstream. When lactate reaches the liver, it is converted to glucose, which muscles utilize as a substrate to generate ATP. Although the biochemical study of lactate metabolism in hepatocytes and skeletal muscle cells has been extensive, the spatial and temporal dynamics of this metabolism in live cells are still unknown. We observed the dynamics of metabolism-related molecules in primary cultured hepatocytes and a skeletal muscle cell line upon lactate overload. Our observations revealed an increase in cytoplasmic pyruvate concentration in hepatocytes, which led to glucose release. Skeletal muscle cells exhibited elevated levels of lactate and pyruvate levels in both the cytoplasm and mitochondrial matrix. However, mitochondrial ATP levels remained unaffected, indicating that the increased lactate can be converted to pyruvate but is unlikely to be utilized for ATP production. The findings suggest that excess lactate in skeletal muscle cells is taken up into mitochondria with little contribution to ATP production. Meanwhile, lactate released into the bloodstream can be converted to glucose in hepatocytes for subsequent utilization in skeletal muscle cells.

PREDICTIVE VALUE OF UMBILICAL ARTERIAL BLOOD LACTATE IN NEONATES WITH MECONIUM-STAINED LIQUOR

This research aims to determine the clinical and maternal variables contributing to increased lactate levels and determine the prognostic usefulness of umbilical cord blood lactate levels in neonates through meconium-stained liquor. The study was conducted between 01 June 2022 and 31 May 2023 at the Department of Neonatology, CMH Rawalpindi. This study included 100 newborns with meconium aspiration syndrome (MAS) in a thin cross-sectional design. Newborn babies received treatment at CMH Hospital throughout the approved period, and observations of umbilical cord blood have been obtained for lactate measurement and arterial blood gas analysis. Furthermore, information on post-delivery problems and neonatal features was retrieved using hospital records. The research included comprehensive statistical analyses, encompassing both Bivariate and multivariate evaluations, to pinpoint the variables linked to increased lactate levels and their potential predictive significance for unfavorable neonatal outcomes. This study included 720 unpaired samples of cord blood from the umbilical artery. The lactate result had an interquartile range of 4.0–6.2 mmol/L and a mean of 5.49 mmol/L (± SD 2.44 mmol/L). After birth, resuscitation was required for a considerably more significant number of neonates with increased lactate levels (25.1%) than for those who had lesser lactate levels (1.3%). At five minutes, Apgar scores of less than seven also showed a significant correlation between high lactate levels and a greater incidence of asphyxia (19.8%). Meconium-stained liquor (aOR=5.85), primigravidity (aOR=2.78), male sex (aOR=1.71), and oxytocic administration (OR=1.97) were factors linked to elevated lactate levels. The results highlight the prognostic significance of umbilical cord blood lactate levels in newborn outcomes, particularly while considering the necessity for resuscitation, asphyxia, and diagnosis such as hypoxic encephalopathy. Elevated lactate levels are more likely in cases where maternal and clinical variables are present, such as primigravidity and liquor stained with meconium. This study underscores the feasibility of including lactate measures from umbilical cord blood into standard evaluations of neonates, providing a valuable instrument for prompt identification and remediation. Prospective investigations and multi-center trials are necessary to confirm these results and investigate the long-term effects of increased lactate levels on newborn health.

The effect of neutrophil lymphocyte ratio and other biochemical parameters on mortality in cancer patients admitted to the emergency department

Aims: To investigate the effectiveness of the neutrophil/lymphocyte ratio and other biochemical parameters in predicting mortality in oncology patients with cancer admitted to the emergency department. Methods: This was a retrospective, observational, single-center study. The study period included a two-year period from January 2014 to December 2015. Demographic data, cancer history and blood tests, emergency department diagnoses, blood parameters evaluated in the emergency department, discharge, and mortality status of the patients were recorded in the data form. The APACHE 2 and SOFA scores of all patients were also calculated. Patients whose data could not be reached were excluded from the study. p&lt;0.05 was considered statistically significant. Results: A total of 180 patients were included in the study. The mean age of the survivor group was 66.4±10.752 years, while the mean age of the non-survivor group was 65.18±13 years. The mean neutrophil/lymphocyte (NLR) ratio of the non-survivor group was 1.0288±11.3, while the NLR of the survivor group was 4.400±3.563. (p&lt;0.05) The mean lactate ratio of the non-survivor group was 2.60±3.384, while the mean lactate ratio of the survivor group was 1.36±1. 090. (p&lt;0.05) When survivor and non-survivor patient groups were compared, a statistically significant difference was observed in mean white blood cell count, neutrophil count, hemoglobin, hematocrit, and blood urea nitrogen (BUN) values. (p&lt;0.05) Conclusion: According to the results of this study, NLR, elevated white blood cell and neutrophil values, decreased hemoglobin and hematocrit, and elevated BUN and lactate levels seem to be predictors of mortality during emergency admissions in cancer patients.

Timing of endoscopy in patients with elevated lactate levels and acute upper gastrointestinal bleeding; a retrospective comparative study

Background/Aims While current guidelines recommend performing endoscopy within 24 h in case of acute upper gastrointestinal bleeding (AUGIB), the precise timing remains an issue of debate. Lactate is an established parameter for risk stratification in a variety of medical emergencies. This study evaluated the predictive ability of elevated lactate levels in identifying patients with UGIB, who may benefit from emergent endoscopy. Methods We retrospectively analyzed all patients with elevated lactate levels, who presented to our emergency department between 01 January 2015 and 31 December 2019 due to suspected AUGIB. Results Of 134 included cases, 81.3% had an Charlson comorbidity index of ≥3 and 50.4% presented with shock. Fifteen (11.2%) patients died and mortality rates rose with increasing lactate levels. Emergent endoscopy within 6 h (EE) and non-EE were performed in 64 (47.8%) and 70 (52.2%) patients, respectively. Patients who underwent EE had lower systolic blood pressure (107.6 mmHg vs. 123.2 mmHg; p = 0.001) and received blood transfusions more frequently (79.7% vs 64.3%; p = 0.048), but interestingly need for endoscopic intervention (26.6% vs 20.0%; p = 0.37), rebleeding (17.2% vs. 15.7%; p = 0.82) and mortality (9.4% vs. 11.4%; p = 0.7) did not differ significantly. Conclusion In conclusion, our findings support the recommendations of current guidelines to perform non-EE after sufficient resuscitation and management of comorbid illnesses.