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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 -
Annals of Surgical Oncology Jun 2022Evidence on the role of curative metastasectomy (CM) for malignant melanoma (MM) patients is limited, especially in the current era of effective systemic therapy. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence on the role of curative metastasectomy (CM) for malignant melanoma (MM) patients is limited, especially in the current era of effective systemic therapy. A systematic review and meta-analysis were performed to ascertain the role of CM compared with incomplete or nonsurgical treatment for patients with MM.
METHODS
Medline, Embase, and Scopus databases were searched for studies investigating CM for MM until 30 September 2021. The review included studies that compared CM with no-CM and reported a hazard ratio (HR) after multivariate analysis for overall survival. A random-effects model with inverse variance was used to calculate pooled HR. The Newcastle-Ottawa Scale was used to assess the risk of bias.
RESULTS
For the final analysis, 40 studies including 31,282 patients (CM, 9958; no-CM, 21,324) were considered. Compared with no-CM, CM was associated with a significantly lower risk of death (HR, 0.42; 95% confidence interval [CI], 0.38-0.47; p < 0.00001). Subgroup analysis showed that the outcome was independent of the effective systemic therapy and anatomic location of metastasis. An unfavorable prognosis was associated with advancing age, elevated lactate dehydrogenase (LDH), male gender, prior stage 3 disease, multiple metastases and organ sites, and shorter disease-free interval.
CONCLUSION
Curative metastasectomy for MM is associated with a lower risk of death than non-curative treatment methods. Selection bias and underlying weakness of studies reduced the strength of evidence in this review. However, CM should be a part of the multimodality treatment of MM whenever technically feasible.
Topics: Humans; Male; Melanoma; Metastasectomy; Prognosis; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35128602
DOI: 10.1245/s10434-022-11351-4 -
The Journal of Applied Laboratory... Sep 2020Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease.
CONTENT
PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2.
SUMMARY
45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 × 109/L), platelet count (MD -22.4 × 109/L), and hemoglobin (MD, -4.1 g/L); all p < 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Diagnostic Tests, Routine; Humans; Outcome Assessment, Health Care; Pandemics; Patient Selection; Pneumonia, Viral; Reference Standards; SARS-CoV-2
PubMed: 32573713
DOI: 10.1093/jalm/jfaa098 -
BMC Pulmonary Medicine Jan 2021COVID-19 is a systemic viral infection which mainly targets the human respiratory system with many secondary clinical manifestations especially affecting the...
BACKGROUND
COVID-19 is a systemic viral infection which mainly targets the human respiratory system with many secondary clinical manifestations especially affecting the hematopoietic system and haemostasis. Few studies have highlighted the prognostic value of blood findings such as lymphopenia, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, LDH, CRP, cardiac troponin, low-density lipoproteins and chest radiographic abnormality. A study of progressions of blood and radiological results may help to identify patients at high risk of severe outcomes. This systematic review aimed to assess the temporal progression of blood and radiology findings of patients with COVID-19.
METHODS
Comprehensive systematic literature search was conducted on Medline, Embase and Cochrane databases to identify articles published for peripheral blood investigation and radiological results of COVID-19 patients.
RESULTS
A total of 27 studies were included in this review. The common laboratory features reported include lymphopenia, elevated levels of C-reactive proteins and lactate dehydrogenase. For radiological signs, ground-glass opacifications, consolidations, and crazy paving patterns were frequently reported. There is a correlation between lymphocyte count, neutrophil count and biomarkers such as C-reactive proteins and lactate dehydrogenase; at a later phase of the disease (more than 7 days since onset of symptoms), lymphopenia worsens while neutrophil count, C-reactive protein levels and lactate dehydrogenase levels increase. Frequencies of ground-glass opacifications and ground-glass opacifications with consolidations decrease at a later phase of the disease while that of consolidation and crazy paving pattern rises as the disease progresses. More extensive lung involvement was also seen more frequently in the later phases.
CONCLUSION
The correlation between temporal progression and the reported blood and radiological results may be helpful to monitor and evaluate disease progression and severity.
Topics: C-Reactive Protein; COVID-19; Disease Progression; Humans; L-Lactate Dehydrogenase; Leukocyte Count; Lung; Lymphopenia; Neutrophils; SARS-CoV-2; Severity of Illness Index
PubMed: 33482780
DOI: 10.1186/s12890-020-01389-z -
Advances in Medical Sciences Sep 2021We conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients.
METHODS
We searched PubMed, Web of Science and Scopus, for studies published between January 2020 and January 2021 that reported CK-MB, COVID-19 severity and mortality (PROSPERO registration number: CRD42021239657).
RESULTS
Fifty-five studies in 11,791 COVID-19 patients were included in the meta-analysis. The pooled results showed that CK-MB concentrations were significantly higher in patients with high disease severity or non-survivor status than patients with low severity or survivor status (standardized mean difference, SMD, 0.81, 95% CI 0.61 to 1.01, p<0.001). The rate of patients with CK-MB values above the normal range was also significantly higher in the former than the latter (60/350 vs 98/1,780; RR = 2.84, 95%CI 1.89 to 4.27, p<0.001; I = 19.9, p = 0.254). Extreme between-study heterogeneity was observed (I = 93.4%, p<0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified (effect size range, 0.77 to 0.84). Begg's (p = 0.50) and Egger's (p = 0.86) t-tests did not show publication bias. In meta-regression analysis, the SMD was significantly and positively associated with the white blood count, aspartate aminotransferase, myoglobin, troponin, brain natriuretic peptide, lactate dehydrogenase, and D-dimer.
CONCLUSIONS
Higher CK-MB concentrations were significantly associated with severe disease and mortality in COVID-19 patients. This biomarker of myocardial injury might be useful for risk stratification in this group.
Topics: Biomarkers; COVID-19; Creatine Kinase, MB Form; Humans; Mortality; SARS-CoV-2; Severity of Illness Index
PubMed: 34256241
DOI: 10.1016/j.advms.2021.07.001 -
Brain, Behavior, and Immunity Jan 2022Bile acids, mainly ursodeoxycholic acid (UDCA) and its conjugated species glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) have long been known to... (Review)
Review
From dried bear bile to molecular investigation: A systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders.
Bile acids, mainly ursodeoxycholic acid (UDCA) and its conjugated species glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) have long been known to have anti-apoptotic, anti-oxidant and anti-inflammatory properties. Due to their beneficial actions, recent studies have started to investigate the effect of UDCA, GUDCA, TUDCA on the same mechanisms in pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders, where increased cell apoptosis, oxidative stress and inflammation in the brain are often observed. A total of thirty-five pre-clinical studies were identified through PubMed/Medline, Web of Science, Embase, PsychInfo, and CINAHL databases, investigating the role of the UDCA, GUDCA and TUDCA in the regulation of brain apoptosis, oxidative stress and inflammation, in pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders. Findings show that UDCA reduces apoptosis, reactive oxygen species (ROS) and tumour necrosis factor (TNF)-α production in neurodegenerative models, and reduces nitric oxide (NO) and interleukin (IL)-1β production in neuropsychiatric models; GUDCA decreases lactate dehydrogenase, TNF-α and IL-1β production in neurological models, and also reduces cytochrome c peroxidase production in neurodegenerative models; TUDCA decreases apoptosis in neurological models, reduces ROS and IL-1β production in neurodegenerative models, and decreases apoptosis and TNF-α production, and increases glutathione production in neuropsychiatric models. In addition, findings suggest that all the three bile acids would be equally beneficial in models of Huntington's disease, whereas UDCA and TUDCA would be more beneficial in models of Parkinson's disease and Alzheimer's disease, while GUDCA in models of bilirubin encephalopathy and TUDCA in models of depression. Overall, this review confirms the therapeutic potential of UDCA, GUDCA and TUDCA in neurological, neurodegenerative and neuropsychiatric disorders, proposing bile acids as potential alternative therapeutic approaches for patients suffering from these disorders.
Topics: Animals; Apoptosis; Bile; Bile Acids and Salts; Brain; Humans; Inflammation; Oxidative Stress; Ursidae
PubMed: 34601012
DOI: 10.1016/j.bbi.2021.09.021 -
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 -
European Journal of Clinical... Nov 2022Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study... (Meta-Analysis)
Meta-Analysis
PURPOSE
Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19.
METHODS
Searches for studies were performed in peer-reviewed and grey-literature from January 1, 2020 to May 23, 2022. The following elements were used to define eligibility criteria: (1) Population: individuals with COVID-19; (2) Intervention: nitazoxanide; (3) Comparison: placebo; (4) Outcomes: primary outcome was death, and secondary outcomes were viral load, positive RT-PCR status, serum biomarkers of inflammation, composite measure of disease progression (ICU admission or invasive mechanical ventilation), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Treatment effects were reported as relative risk (RR) for dichotomous variables and standardized mean difference (SMD) for continuous variables with 95% confidence intervals (CI).
RESULTS
Five blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load (SMD = - 0.16; 95% CI - 0.38 to 0.05) and the frequency of positive RTP-PCR results (RR = 0.92; 95% CI 0.81 to 1.06). In addition, there was no decreased risk for disease progression (RR = 0.63; 95% CI 0.38 to 1.04) and death (RR = 0.81; 95% CI 0.36 to 1.78) among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells (SMD = - 0.15; 95% - 0.29 to - 0.02), lactate dehydrogenase (LDH) (SMD - 0.32; 95% - 0.52 to - 0.13), and D-dimer (SMD - 0.49; 95% CI - 0.68 to - 0.31) compared to placebo, but the magnitude of effect was considered small to moderate.
CONCLUSION
This systematic review showed no evidence of clinical benefits of the use of nitazoxanide to treat patients with mild or moderate COVID-19. In addition, we found a reduction in WBC, LDH, and D-dimer levels among nitazoxanide-treated patients, but the effect size was considered small to moderate.
Topics: Anti-Inflammatory Agents; Antiparasitic Agents; Antiviral Agents; Disease Progression; Humans; Lactate Dehydrogenases; Nitro Compounds; Randomized Controlled Trials as Topic; SARS-CoV-2; Thiazoles; COVID-19 Drug Treatment
PubMed: 36066651
DOI: 10.1007/s00228-022-03380-5 -
Urologic Oncology Apr 2023Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel.
METHODS
PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel.
RESULTS
Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99).
CONCLUSIONS
Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit.
Topics: Male; Humans; Docetaxel; Prostatic Neoplasms, Castration-Resistant; Prognosis; Prostate-Specific Antigen; Treatment Outcome; Hemoglobins
PubMed: 35970698
DOI: 10.1016/j.urolonc.2022.06.018 -
The American Journal of Emergency... Mar 2021Laboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of COVID-19 outcomes. This systematic review and meta-analysis aimed to evaluate the difference between these parameters in severe and nonsevere disease and to provide the optimal cutoff value for predicting severe disease.
METHOD
We performed a systematic literature search through electronic databases. The variables of interest were serum procalcitonin, albumin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) levels in each group of severity outcomes from COVID-19.
RESULTS
There were a total of 4848 patients from 23 studies. Our meta-analysis suggest that patients with severe COVID-19 infections have higher procalcitonin, (mean difference 0.07; 95% CI 0.05-0.10; p < 0.00001), CRP (mean difference 36.88; 95% CI 29.10-44.65; p < 0.00001), D-Dimer (mean difference 0.43; 95% CI 0.31-0.56; p < 0.00001), and LDH (mean difference 102.79; 95% CI 79.10-126.49; p < 0.00001) but lower levels of albumin (mean difference -4.58; 95% CI -5.76 to -3.39; p < 0.00001) than those with nonsevere COVID-19 infections. The cutoff values for the parameters were 0.065 ng/mL for procalcitonin, 38.85 g/L for albumin, 33.55 mg/L for CRP, 0.635 μ/L for D-dimer, and 263.5 U/L for LDH, each with high sensitivity and specificity.
CONCLUSION
This meta-analysis suggests elevated procalcitonin, CRP, D-dimer, and LDH and decreased albumin can be used for predicting severe outcomes in COVID-19.
Topics: Biomarkers; C-Reactive Protein; COVID-19; COVID-19 Serological Testing; Fibrin Fibrinogen Degradation Products; Humans; L-Lactate Dehydrogenase; Procalcitonin; Prognosis; Risk Assessment; SARS-CoV-2; Serum Albumin; Severity of Illness Index
PubMed: 33418211
DOI: 10.1016/j.ajem.2020.12.076