Combination Of Lactate Dehydrogenase Research Articles

- Mechanism of LDH and IL-8 Involved in pancreatic cancer Pain and the Correlation of Pain Degree

Objective: To observe the mechanism of lactate dehydrogenase (LDH) and interleukin 8 (IL-8) in pancreatic cancer pain and their correlation with pain degree. Methods: 126 patients with pancreatic cancer who visited our hospital from January 2021 to February 2023 were selected. The patients were divided into 58 patients with low pain (1~3 points) and 68 patients with high pain (4~10 points) by visual analog scale (VAS). And 50 health examinees in the same period were selected as the healthy control group. The serum LDH and IL-8 concentrations are analyzed by enzyme-linked immunosorbent assay, as well as the subjective pain grading method scoreis analyzed. The differences in LDH and IL-8 concentrations among the three groups of patients were compared. Pearson correlation analysis was used to investigate the correlation between LDH, IL-8 concentrations and patient pain. Binary logistic regression was used to determine independent risk factors for high pain, and ROC curves were used to analyze the diagnostic efficacy of each indicator. Result: The serum LDH and IL-8 concentrations in the high pain group were exceed the low pain group’s (P<0.05). The serum LDH and IL-8 concentrations in the low pain groupexceed the healthy control group’s(P<0.05). Pearson correlation analysis revealed a positive correlation between serum LDH concentration and pain grading (r=0.736, P=0.000). The serum IL-8 has positive correlation with pain grading (r=0.680, P=0.000). Serum LDH and IL-8 concentrations have positive correlation(r=0.589, P=0.000). LDH and IL-8 concentrations are independent risk factors for high pain levels (OR=1.033, 1.142, P<0.05). The logistic regression prediction model formula was used: Y=constant+B1X1+B2X2+...+BnXn to set the joint diagnostic prediction model as -12.063+0.033×LDH+0.133×IL-8. The areas under the ROC curves of LDH, IL-8, and predictive model (LDH+IL-8) in patients with high pain were 0.925, 0.945, and 0.974, respectively. The relevant standards for LDH are>190U/L, IL-8 is>36pg/mL, and the relevant standards for prediction models are>5.75. Conclusion: LDH and IL-8 participate in the pain aggravation process of pancreatic cancer, and are closely related to the pain grading. The combination of LDH and IL-8 can be used as a biological indicator to evaluate the pain severity of pancreatic cancer, and provide reference for clinical diagnosis and treatment.

Prognostic value of neutrophil-to-lymphocyte ratio, lactate dehydrogenase, D-dimer, and computed tomography score in patients with coronavirus disease 2019.

Background: This study aimed to explore the significance of neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), D-dimer, and CT score in evaluating the severity and prognosis of coronavirus disease 2019 (COVID-19).Methods: Patients with laboratory-confirmed COVID-19 were retrospectively enrolled. The baseline data, laboratory findings, chest computed tomography (CT) results evaluated by CT score on admission, and clinical outcomes were collected and compared. Logistic regression was used to assess the independent relationship between the baseline level of the four indicators (NLR, LDH, D-dimer, and CT score) and the severity of COVID-19.Results: Among the 432 patients, 125 (28.94%) and 307 (71.06%) were placed in the severe and non-severe groups, respectively. As per the multivariate logistic regression, high levels of NLR and LDH were independent predictors of severe COVID-19 (OR=2.163; 95% CI=1.162-4.026; p=0.015 for NLR>3.82; OR=2.298; 95% CI=1.327-3.979; p=0.003 for LDH>246 U/L). Combined NLR>3.82 and LDH>246 U/L increased the sensitivity of diagnosis in patients with severe disease (NLR>3.82 [50.40%] vs. combined diagnosis [72.80%]; p=0.0007; LDH>246 [59.2%] vs. combined diagnosis [72.80%]; p<0.0001).Conclusions: High levels of serum NLR and LDH have potential value in the early identification of patients with severe COVID-19. Moreover, the combination of LDH and NLR can improve the sensitivity of diagnosis.

Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy.

Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel. Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical outcomes were assessed. CTCs were detected in 88% of blood samples from patients with melanoma. CTC-derived biomarkers and clinical variables analyzed using classification and regression tree analysis revealed that a combination of lactate dehydrogenase, CTC-mRNA biomarkers, and tumor BRAF-mutation status was indicative of clinical outcomes for patients with stage IV melanoma (n = 52). The panel stratified low-risk and high-risk patients, whereby the latter had poor disease-free (P = 0.03) and overall survival (P = 0.02). Incorporation of a DNA biomarker with mRNA profiling increased overall CTC-detection capability by 57% compared to mRNA profiling only. RNA sequencing of isolated CTCs identified significant catenin beta 1 (CTNNB1) overexpression (P <0.01) compared to nondisease donor blood. CTC-CTNNB1 was associated with progressive disease/stable disease compared to complete-responder patient status (P = 0.02). Serial CTC profiling identified subclinical disease in patients who developed progressive disease during treatment/follow-up. CTC-derived mRNA/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.

Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Biomarkers of Immune-Checkpoint Inhibitor for Non-Small Cell Lung Cancer

BackgroundThe Gustave Roussy Immune Score (GRIm-Score) and the Royal Marsden Hospital prognostic score (RMH score) were recently developed in order to improve a better participant selection for phase I trials. The GRIm-Score is formed by combination of lactate dehydrogenase (LDH), serum albumin concentration, and neutrophil-to-lymphocyte ratio (NLR). The RMH score is calculated by LDH, albumin, and number of metastases. These two scores have been validated only in phase I trials. The purpose of this study was to assess whether these scores are useful for practical treatment of immune-checkpoint inhibitor (ICI) monotherapy in pretreated non-small cell lung cancer (NSCLC).MethodsThis was a retrospective and single-centered study of 76 NSCLC patients treated with ICI monotherapy between December 2015 and October 2018 at our hospital. We divided 76 patients into high and low GRIm-Score and RMH score groups. Comparison of overall survival (OS) and progression free survival (PFS) was performed by Kaplan-Meier curves and log-rank tests. Independent prognostic factors of OS and PFS were analyzed by multivariate Cox proportional hazard analyses.ResultsThe OS of the high GRIm-Score group was significantly shorter than that of the low score group (low vs. high; median 19.9 vs. 3.2 months, P < 0.01), while no significant difference was observed in PFS (2.6 vs. 2.1 months, P = 0.13). The PFS of the high RMH score was significantly shorter than that of the low score group (low vs. high; 2.6 vs. 1.8 months, P = 0.01), while there was no significant difference in OS (16.0 vs. 10.4, P = 0.24). Multivariate analyses detected high GRIm-Score (hazard ratio (HR) 3.93, 95% confidence interval (CI) 2.04 - 7.58, P < 0.01), and high RMH score (HR 1.76, 95% CI 1.03 - 3.02, P = 0.04) as poor prognostic factors of OS and PFS, respectively.ConclusionsBaseline GRIm-Score and RMH score were independent prognostic factors of OS and PFS of ICI monotherapy for pretreated NSCLC patients, respectively. These two scores are not only selection biomarkers for patients in experimental trials, but also useful prognostic biomarkers for NSCLC patients practically treated with ICI therapy.

Diagnostic value of combination serum assay of lactate dehydrogenase, D-dimer, and C-reactive protein for uterine leiomyosarcoma.

Leiomyosarcoma is the most common type of uterine sarcoma. In some leiomyosarcoma cases, preoperative diagnosis might be difficult, and they might be treated as benign lesions. We evaluated diagnostic values of preoperative serum lactate dehydrogenase (LDH), D-dimer and C-reactive protein for differentiating leiomyosarcoma. From 2008 to 2013, leiomyosarcoma cases in three university hospitals were enrolled. Preoperative serum LDH, D-dimer and C-reactive protein were analyzed if tested. These markers of pathologically diagnosed leiomyoma cases presumed benign (group B) and presumed malignant (group PM) were compared with those of leiomyosarcoma cases (group S). Groups S, PM and B had 36, 28 and 69 cases, respectively. Positive rates of LDH were 66.7%, 14.3% and 0% in groups S, PM and B, respectively. Positive rates of D-dimer and C-reactive protein were 83.3% and 64.5%, 17.9% and 10.7% and 5% and 2.9% in groups S, PM and B, respectively. Positive rates of all three markers were high in the order of leiomyosarcoma, atypical leiomyoma and typical leiomyoma. In group PM, 12 (63.2%) cases were negative for all three markers, whereas 1 (3.3%) case was negative in group S. No case was positive for all markers in group PM, whereas 41.2% leiomyosarcoma cases were positive for all markers. When all parameters were positive, specificity and positive predictive value were 100% in differentiating leiomyosarcoma from group PM. Combination of LDH, D-dimer and C-reactive protein could be useful for distinguishing leiomyosarcoma from especially degenerated or atypical leiomyoma.

Combination of lactate dehydrogenase and tumor mutational burden to predict clinical benefit of anti-CTLA-4 therapy in melanoma.

e15029Background: Tumor mutational burden (TMB) has been revealed to be associated with the clinical outcome of immune checkpoint blockade (ICB). Nevertheless, part of patients with relatively lowe...

Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma.

Serum enzymes, including lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), have recently been reported to play important roles in tumor growth. Increases in LDH and ALP have been confirmed to predict poor prognosis in patients with various cancers. However, their prognostic value in pancreatic cancer has not been well studied. Therefore, we reviewed the preoperative data on LDH and ALP in 185 pancreatic ductal adenocarcinoma (PDAC) patients who underwent surgery between July 2005 and December 2010 to explore the prognostic value of these markers. The cutoff points were determined based on the upper limit of their normal values. The Chi-square test was used to analyze the relationships between LDH/ALP and clinical characteristics. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). We found that elevation of LDH was related to carbohydrate antigen 19-9 (CA19-9), lymph node involvement, tumor size, TNM, distant metastasis, and recurrence. Additionally, ALP was correlated to perineural invasion. After multivariate analysis, LDH and ALP were identified as independent prognostic factors for DFS and OS, and elevation of LDH/ALP was correlated with poor DFS and OS. Notably, there was a positive correlation between LDH and ALP. The predictive power of LDH combined with ALP was more sensitive than that of either one alone. Therefore, we conclude that the preoperative LDH and ALP values are prognostic factors for PADC, and the prognostic accuracy of testing can be enhanced by the combination of LDH and ALP

Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, complement-mediated hemolysis, frequently leading to debilitating clinical symptoms and life-threatening complications such as thromboembolism (TE). A retrospective analysis was performed on 301 patients from the South Korean National PNH Registry to describe disease burden and identify TE-associated risk factors. TE was identified in 18 % of patients and was associated with increased risk for mortality [odds ratio (OR), 6.85; P < 0.001]. A multivariate analysis showed that PNH patients with elevated hemolysis [lactate dehydrogenase (LDH) levels ≥1.5 times the upper limit of normal (ULN)] at diagnosis were at significantly higher risk for TE than patients with LDH <1.5 × ULN (OR 7.0; P = 0.013). The combination of LDH ≥1.5 × ULN with the clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria was associated with a greater increased risk for TE than elevated hemolysis or clinical symptoms alone. Continuous monitoring of these risk factors is critical for identifying PNH patients at risk for morbidities and mortality and allowing early intervention.

Risk of Thromboembolism in Patients with Paroxysmal Nocturnal Hemoglobinuria Presenting with Both Clinical Symptoms and Elevated Hemolysis

AbstractAbstract 1273 Background:Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disorder characterized by chronic complement-mediated hemolysis. Chronic hemolysis is associated with an increased risk of thromboembolism (TE), the major cause of end organ damage and early mortality in PNH. Patients with PNH frequently experience clinical symptoms such as abdominal pain, chest pain, dyspnea, and hemoglobinuria. Pain and dyspnea are a likely consequence of vasoconstriction due to sequestering of nitric oxide by free hemoglobin released during hemolysis. These symptoms not only cause patient distress but may be indicative of advanced disease and an increased risk of TE. Objective:To evaluate if the risk of TE is increased in PNH patients with increased hemolysis, measured by lactate dehydrogenase (LDH) serum levels ≥1.5-fold higher than the upper limit of normal (LDH ≥1.5×ULN), plus any of the four clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria during the course of the disease, compared with patients who had an individual clinical symptom or LDH ≥1.5×ULN alone. Methods:This study included 224 PNH patients from the South Korean national PNH registry. In patients with LDH ≥1.5×ULN at diagnosis, associations between the presence of the four individual clinical symptoms and the incidence of TE were analyzed using logistic regression. The effect of multiple symptoms including LDH ≥1.5×ULN on the TE rate was assessed using odds ratios (OR) and associated 95% confidence intervals (CIs). Results:The results of the analyses between clinical symptoms, LDH ≥1.5×ULN, and the incidence of TEs are tabulated below. The risk of TE was significantly increased in patients with LDH ≥1.5×ULN (OR: 8.57; P<0.001) or who had abdominal pain, chest pain or dyspnea (OR: range 2.74–2.86; P≤0.022) during the course of the disease compared with patients without these individual symptoms. The risk of TE was further increased in patients with both LDH ≥1.5×ULN and at least one of the four symptoms compared with patients with LDH ≥1.5×ULN alone (OR: 9.20; P=0.032). Individual symptom analyses showed that patients with each symptom and LDH ≥1.5×ULN had a significantly increased risk of TE compared with patients without the symptom and LDH <1.5×ULN. This was particularly evident for abdominal pain and chest pain (OR: 17.79 and 19.04, respectively; P≤0.006) but also seen in patients with dyspnea or hemoglobinuria (OR: 10.28 and 10.35, respectively; P≤0.025). These results suggest that the combination of LDH ≥1.5×ULN and one or more of these clinical symptoms poses a much greater risk of a TE than any of the individual factors alone. Conclusions:These data confirm that hemolysis, identified by LDH ≥1.5×ULN, is a significant risk factor for TE in PNH patients. Importantly, the risk of TE was further increased in patients with both elevated hemolysis and symptoms of abdominal pain, chest pain, dyspnea or hemoglobinuria compared with patients with elevated hemolysis alone. These results suggest that early intervention is important for PNH patients with both elevated hemolysis and clinical symptoms, and also highlight the need for careful monitoring of clinical symptoms that signal an elevated clinical risk for TE.Interaction of Clinical Symptom with HemolysisaPatients with TE, n/N (%)OR for TE95% CIP ValueLDH <1.5 × ULN vs2/53 (3.8)8.572.00, 36.68<0.001LDH ≥1.5 × ULN43/171 (25.1)Abdominal pain (−) vs13/115 (11.3)Abdominal pain (+)32/109 (29.4)2.791.35, 5.760.006Abdominal pain (−), LDH <1.5 × ULN vs1/36 (2.8)Abdominal pain (+), LDH ≥1.5 × ULN31/92 (33.7)17.792.33, 136.010.006Chest pain (−) vs34/194 (17.5)Chest pain (+)11/30 (36.7)2.741.15, 6.510.022Chest pain (−), LDH <1.5 × ULN vs2/47 (4.3)Chest pain (+), LDH ≥1.5 × ULN11.24 (45.8)19.043.74, 96.99<0.001Dyspnea (−) vs17/133 (12.8)Dyspnea (+)28/91 (30.8)2.861.43, 5.720.003Dyspnea (−), LDH <1.5 × ULN vs2/36 (5.6)Dyspnea (+), LDH ≥1.5 × ULN28/74 (37.8)10.352.31, 46.450.002Hemoglobinuria (−) vs15/92 (16.3)Hemoglobinuria (+)30/132 (22.7)1.280.63, 2.600.493Hemoglobinuria (−), LDH <1.5× ULN vs1/29 (3.4)Hemoglobinuria (+), LDH ≥1.5× ULN (+)29/108 (26.9)10.281.34, 79.020.025aComparisons adjusted for presence(+) or absence (-) of other clinical symptoms. Disclosures:Lee:Alexion Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jang:Alexion Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Hydrogen Evolution from L-Lactate and L-Malate with the Combination of Lactate Dehydrogenase or Malate Dehydrogenase and Hydrogenase from A. Eutrophus H16

Hydrogen evolution system from L-lactate and L-malate consisting of lactate dehydrogenase or malate dehydrogenase and hydrogenase from cell free extracts of Alcaligenes eutrophus H16 was established. When the solution containing L-lactate, lactate dehydrogenase, NAD and hydrogenase was incubated at 30°C hydrogen evolution was observed. Similarly, the hydrogen evolution was also observed from the L-malate incubated at 30°C.