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PloS One 2016Recently, many studies have shown that the serum lactate dehydrogenase (LDH) level is related to the prognosis of renal cell carcinoma (RCC). We launched this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recently, many studies have shown that the serum lactate dehydrogenase (LDH) level is related to the prognosis of renal cell carcinoma (RCC). We launched this meta-analysis to assess the prognostic value of serum LDH in patients with RCC.
METHODS
We searched PubMed, Embase and Web of Science for information on serum LDH and the outcome of RCC through June 14, 2016. The hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) were extracted and integrated from the matching studies.
RESULTS
A total of 29 studies including 6629 patients with RCC were incorporated in this meta-analysis. Patients whose serum LDH levels were elevated had a lower OS (HR = 2.13, 95% CI = 1.69-2.69, P < 0.001). Meanwhile, the pooled data showed that a higher serum LDH level was a negative prognostic factor for PFS (HR = 1.74, 95% CI = 1.48-2.04, P < 0.001). Furthermore, subgroup analyses indicated elevated serum LDH was associated with poor survival in different tumor types. Elevated serum LDH was significantly associated with worse prognosis for patients with all stages of RCC (OS, HR = 2.41, 95% CI = 1.09-5.33), metastatic RCC (OS, HR = 2.62, 95% CI 1.57-2.59; CSS, HR = 1.79, 95% CI 1.49-2.15), and non-metastatic RCC (OS, HR = 3.67, CI = 1.33-10.13). Besides, elevated serum LDH also indicated a worse prognosis in subgroups of cut-off values, analysis types and ethnicity.
CONCLUSIONS
Our results show that serum LDH levels are associated with the outcomes of RCC and can be used as a valuable biomarker for monitoring prognoses.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; L-Lactate Dehydrogenase; Proportional Hazards Models; Publication Bias; ROC Curve
PubMed: 27861542
DOI: 10.1371/journal.pone.0166482 -
The Cochrane Database of Systematic... Apr 2017The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum... (Review)
Review
BACKGROUND
The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic necrosis in people with acute pancreatitis, so that an informed decision can be made as to whether the person with pancreatic necrosis needs further investigations such as computed tomography (CT) scan or magnetic resonance imaging (MRI) scan and treatment for pancreatic necrosis started. There is currently no standard clinical practice, although CRP, particularly an increasing trend of CRP, is often used as a triage test to determine whether the person requires further imaging. There is also currently no systematic review of the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis.
OBJECTIVES
To compare the diagnostic accuracy of CRP, procalcitonin, or LDH (index test), either alone or in combination, in the diagnosis of necrotising pancreatitis in people with acute pancreatitis and without organ failure.
SEARCH METHODS
We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.
SELECTION CRITERIA
We included all studies that evaluated the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis using the following reference standards, either alone or in combination: radiological features of pancreatic necrosis (contrast-enhanced CT or MRI), surgeon's judgement of pancreatic necrosis during surgery, or histological confirmation of pancreatic necrosis. Had we found case-control studies, we planned to exclude them because they are prone to bias; however, we did not locate any. Two review authors independently identified the relevant studies from the retrieved references.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, including methodological quality assessment, from the included studies. As the included studies reported CRP, procalcitonin, and LDH on different days of admission and measured at different cut-off levels, it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) on each of the different days of admission and measured at different cut-off levels.
MAIN RESULTS
A total of three studies including 242 participants met the inclusion criteria for this review. One study reported the diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279 mg/L) without stating the day on which the CRP was measured. One study reported the diagnostic performance of procalcitonin on day 1 (1 day after admission) using a threshold level of 0.5 ng/mL. One study reported the diagnostic performance of CRP on day 3 (3 days after admission) using a threshold level of 140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290 U/L. The sensitivities and specificities varied: the point estimate of the sensitivities ranged from 0.72 to 0.88, while the point estimate of the specificities ranged from 0.75 to 1.00 for the different index tests on different days of hospital admission. However, the confidence intervals were wide: confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of specificities ranged from 0.18 to 1.00 for the different tests on different days of hospital admission. Overall, none of the tests assessed in this review were sufficiently accurate to suggest that they could be useful in clinical practice.
AUTHORS' CONCLUSIONS
The paucity of data and methodological deficiencies in the studies meant that it was not possible to arrive at any conclusions regarding the diagnostic test accuracy of the index test because of the uncertainty of the results. Further well-designed diagnostic test accuracy studies with prespecified index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at least two weeks to ensure that the person does not have pancreatic necrosis, as early scans may not indicate pancreatic necrosis); and clearly defined reference standards (of surgical or radiological confirmation of pancreatic necrosis) are important to reliably determine the diagnostic accuracy of CRP, procalcitonin, and LDH.
Topics: Acute Disease; Biomarkers; C-Reactive Protein; Calcitonin; Confidence Intervals; Diagnosis, Differential; Humans; L-Lactate Dehydrogenase; Pancreatitis; Pancreatitis, Acute Necrotizing; Sensitivity and Specificity
PubMed: 28431197
DOI: 10.1002/14651858.CD012645 -
Medicine Aug 2022Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed... (Meta-Analysis)
Meta-Analysis
Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs.
METHODS
A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity.
RESULTS
A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries.
CONCLUSION
Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; L-Lactate Dehydrogenase; Lymphocytes; Melanoma; Neutrophils; Prognosis
PubMed: 35960066
DOI: 10.1097/MD.0000000000029536 -
Postgraduate Medical Journal Jun 2022This meta-analysis aimed to evaluate the prognostic performance of elevated lactate dehydrogenase (LDH) in patients with COVID-19. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis aimed to evaluate the prognostic performance of elevated lactate dehydrogenase (LDH) in patients with COVID-19.
METHODS
A systematic literature search was performed using PubMed, Embase and EuropePMC on 19 November 2020. The outcome of interest was composite poor outcome, defined as a combined endpoint of mortality, severity, need for invasive mechanical ventilation and need for intensive care unit care. Severity followed the included studies' criteria.
RESULTS
There are 10 399 patients from 21 studies. Elevated LDH was present in 44% (34%-53%) of the patients. Meta-regression analysis showed that diabetes was correlated with elevated LDH (OR 1.01 (95% CI 1.00 to 1.02), p=0.038), but not age (p=0.710), male (p=0.068) and hypertension (p=0.969). Meta-analysis showed that elevated LDH was associated with composite poor outcome (OR 5.33 (95% CI 3.90 to 7.31), p<0.001; I: 77.5%). Subgroup analysis showed that elevated LDH increased mortality (OR 4.22 (95% CI 2.49 to 7.14), p<0.001; I: 89%). Elevated LDH has a sensitivity of 0.74 (95% CI 0.60 to 0.85), specificity of 0.69 (95% CI 0.58 to 0.78), positive likelihood ratio of 2.4 (95% CI 1.9 to 2.9), negative likelihood ratio of 0.38 (95% CI 0.26 to 0.55), diagnostic OR of 6 (95% CI 4 to 9) and area under curve of 0.77 (95% CI 0.73 to 0.80). Elevated LDH would indicate a 44% posterior probability and non-elevated LDH would in indicate 11% posterior probability for poor prognosis. Meta-regression analysis showed that age, male, hypertension and diabetes did not contribute to the heterogeneity of the analyses.
CONCLUSION
LDH was associated with poor prognosis in patients with COVID-19.
PROSPERO REGISTRATION NUMBER
CRD42020221594.
Topics: COVID-19; Diabetes Mellitus; Humans; Hypertension; L-Lactate Dehydrogenase; Lactate Dehydrogenases; Male; Prognosis
PubMed: 33452143
DOI: 10.1136/postgradmedj-2020-139542 -
International Journal of Surgery... Jul 2020To date, there remain uncertainties over the prognostic role of serum lactate dehydrogenase (LDH) in patients with metastatic renal cell carcinoma (mRCC). A systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, there remain uncertainties over the prognostic role of serum lactate dehydrogenase (LDH) in patients with metastatic renal cell carcinoma (mRCC). A systematic review and meta-analysis was performed.
MATERIALS AND METHODS
Eligible studies were retrieved from PubMed, Embase, Cochrane Library and Web of Science databases up to October 2019. The endpoints included overall survival (OS) and progression-free survival (PFS). Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate each endpoint.
RESULTS
Thirty observational studies of low to moderate risk of bias embracing 6754 patients with mRCC were included. The results showed that patients with a high pretreatment serum LDH had an inferior OS (HR: 2.15, 95% CI: 1.85-2.51; P < 0.001) and PFS (HR: 1.76, 95% CI: 1.49-2.10; P < 0.001). Subgroup analyses according to year of publication, study design, patient population, geographic region, sample size and NOS score did not alter the direction of results. There was significant publication bias for OS, but not for PFS. Sensitivity analyses further confirmed the robustness of the results.
CONCLUSION
Our findings indicated that a high level of pretreatment serum LDH was associated with an inferior OS and DFS in patients with mRCC. Methodological limitations should be considered while interpreting these results.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; L-Lactate Dehydrogenase; Neoplasm Metastasis; Prognosis
PubMed: 32417461
DOI: 10.1016/j.ijsu.2020.05.019 -
Annals of Translational Medicine Apr 2019Bevacizumab, a humanized monoclonal antibody against vascular epithelial growth factor, plays a significant role in first-line, second-line, beyond-progression, and...
Baseline serum lactate dehydrogenase level predicts survival benefit in patients with metastatic colorectal cancer receiving bevacizumab as first-line chemotherapy: a systematic review and meta-analysis of 7 studies and 1,219 patients.
BACKGROUND
Bevacizumab, a humanized monoclonal antibody against vascular epithelial growth factor, plays a significant role in first-line, second-line, beyond-progression, and maintenance treatment of patients with metastatic colorectal carcinoma (mCRC). Nevertheless, there are currently no biomarkers available to predict patient response or resistance to bevacizumab, which would be useful in clinical trials.
METHODS
Using PRISMA guidelines, we conducted a systematic review and meta-analysis of the association between serum lactate dehydrogenase (LDH) level and progression-free survival (PFS), overall survival (OS), and objective response rate in mCRC patients treated with bevacizumab-based first-line chemotherapy. A comprehensive, computerized literature search of PubMed, the Web of Science, Scopus, Ovid, and the gray literature was performed. Only studies conforming to specific eligibility criteria were included. Pooled hazard ratios (HRs) were estimated using random-effects or fixed-effects models according to heterogeneity between studies. Sensitivity analysis was conducted to evaluate the stability of the results by removing each individual study from the meta-analysis.
RESULTS
Seven eligible studies of 1,219 total patients were included in the analysis. Meta-analysis of all studies revealed that high serum LDH level is associated with shorter PFS (HR: 1.43, 95% CI: 1.05-1.94; P=0.023) and OS (HR: 1.667, 95% CI: 1.230-2.259; P=0.001) times in mCRC patients treated with bevacizumab-based first-line chemotherapy. However, there was no significant association between serum LDH and objective response rate.
CONCLUSIONS
High serum LDH level is significantly associated with shorter PFS and OS time and may have utility as a prognostic factor for mCRC patients receiving bevacizumab as first-line chemotherapy and as a predictive factor for those receiving bevacizumab-based therapy at other times.
PubMed: 31157254
DOI: 10.21037/atm.2019.02.45 -
Scientific Reports Apr 2015Although most studies have reported that high serum lactate dehydrogenase (LDH) levels are associated with poor prognosis in several malignancies, the consistency and... (Meta-Analysis)
Meta-Analysis Review
Although most studies have reported that high serum lactate dehydrogenase (LDH) levels are associated with poor prognosis in several malignancies, the consistency and magnitude of the impact of LDH are unclear. We conducted the first comprehensive meta-analysis of the prognostic relevance of LDH in solid tumors. Overall survival (OS) was the primary outcome; progression-free survival (PFS) and disease-free survival (DFS) were secondary outcomes. We identified a total of 68 eligible studies that included 31,857 patients. High LDH was associated with a HR for OS of 1.48 (95% CI = 1.43 to 1.53; P < 0.00001; I(2) = 93%), an effect observed in all disease subgroups, sites, stages and cutoff of LDH. HRs for PFS and DFS were 1.70 (95% CI = 1.44 to 2.01; P < 0.00001; I(2) = 13%) and 1.86(95% CI = 1.15 to 3.01; P = 0.01; I(2) = 88%), respectively. Analysis of LDH as a continuous variable showed poorer OS with increasing LDH (HR 2.11; 95% CI = 1.35 to 3.28). Sensitivity analyses showed there was no association between LDH cutoff and reported HR for OS. High LDH is associated with an adverse prognosis in many solid tumors and its additional prognostic and predictive value for clinical decision-making warrants further investigation.
Topics: Antineoplastic Agents; Databases, Factual; Disease-Free Survival; Humans; L-Lactate Dehydrogenase; Neoplasms; Prognosis; Proportional Hazards Models; Survival Rate
PubMed: 25902419
DOI: 10.1038/srep09800 -
Journal of Cancer Research and Clinical... Dec 2023Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance.
METHODS
A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS).
RESULTS
The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult.
CONCLUSION
In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.
Topics: Humans; Prognosis; Immune Checkpoint Inhibitors; B7-H1 Antigen; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Biomarkers; Tumor Microenvironment
PubMed: 38078963
DOI: 10.1007/s00432-023-05504-5 -
Melanoma Research Feb 2019Levels of serum lactate dehydrogenase (LDH) are a recognized prognostic factor in malignant melanoma (MM). It is relevant to confirm its prognostic role in patients... (Meta-Analysis)
Meta-Analysis
Prognostic and predictive role of elevated lactate dehydrogenase in patients with melanoma treated with immunotherapy and BRAF inhibitors: a systematic review and meta-analysis.
Levels of serum lactate dehydrogenase (LDH) are a recognized prognostic factor in malignant melanoma (MM). It is relevant to confirm its prognostic role in patients treated with targeted therapies [BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi)] and immunotherapy (IT). Furthermore, its role as a predictive marker in patients treated with these drugs had still not been investigated. We performed an electronic search for studies reporting information on overall survival (OS) or progression-free survival (PFS) according to LDH levels and on their predictive effect in patients treated with targeted therapies (BRAFi and MEKi) and IT. Data were pooled using hazard ratios (HRs) for OS and HRs for PFS according to a fixed-effect or a random-effect model. For predictive analysys, effect of new agents versus standard therapy was evaluated in LDH high population. A total of 71 publications were retrieved for a total of 16 159 patients. Overall, elevated LDH levels were associated with an HR for OS of 1.72 [95% confidence interval (CI): 1.6-1.85; P<0.0001]. Similarly, HR for PFS was 1.83 (95% CI: 1.53-2.2; P<0.0001). In the LDH elevated subgroup, new agents improved OS significantly (HR: 0.71; 95% CI: 0.62-0.82; P<0.0001) and PFS (HR: 0.63; 95% CI: 0.55-0.72; P<0.0001). In advanced MM treated with IT or BRAFi±MEKi, elevated LDH level at baseline represents a poor prognostic factor. However, patients with increased LDH levels and treated with these drugs gain significant benefits in terms of PFS and OS.
Topics: Biomarkers, Tumor; Drug Therapy, Combination; Humans; Immunotherapy; L-Lactate Dehydrogenase; Melanoma; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Skin Neoplasms
PubMed: 30308577
DOI: 10.1097/CMR.0000000000000520 -
Tuberculosis and Respiratory Diseases Jan 2024Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) are often difficult to differentiate owing to the overlapping clinical features. Observational...
BACKGROUND
Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) are often difficult to differentiate owing to the overlapping clinical features. Observational studies demonstrate that the ratio of lactate dehydrogenase to adenosine deaminase (LDH/ADA) is lower in TPE compared to PPE, but integrated analysis is warranted.
METHODS
We conducted a systematic review to evaluate the diagnostic accuracy of the LDH/ADA ratio in differentiating TPE and PPE. We explored the PubMed and Scopus databases for studies evaluating the LDH/ADA ratio in differentiating TPE and PPE.
RESULTS
From a yield of 110 studies, five were included for systematic review. The cutoff value for the LDH/ADA ratio in TPE ranged from <14.2 to <25. The studies demonstrated high heterogeneity, precluding meta-analysis. Quality Assessment of Diagnostic Accuracy Studies Tool 2 assessment revealed a high risk of bias in terms of patient selection and index test.
CONCLUSION
LDH/ADA ratio is a potentially useful parameter to differentiate between TPE and PPE. Based on the limited data, we recommend an LDH/ADA ratio cutoff value of <15 in differentiating TPE and PPE. However, more rigorous studies are needed to further validate this recommendation.
PubMed: 37726943
DOI: 10.4046/trd.2023.0107