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Clinica Chimica Acta; International... Nov 2020Hemolysis is one of the main pathophysiological characteristics of sickle cell disease (SCD) and might cause or could be the result of oxidative stress. Antioxidants are... (Review)
Review
Hemolysis is one of the main pathophysiological characteristics of sickle cell disease (SCD) and might cause or could be the result of oxidative stress. Antioxidants are studied in SCD due to their potential to ensure redox balance and minimize deleterious effects on erythrocyte membranes. The objective of this systematic review was to evaluate the efficacy of antioxidant nutrient supplementation on reducing hemolysis in SCD patients through randomized clinical trials. We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Cochrane Handbook for Systematic Reviews of Interventions investigating whether antioxidants could improve the hemolytic status of SCD patients. This study included 587 articles published until April 2020. We reduced this pool to 12 articles by excluding duplicates, reviews, comments, and studies with non-human subjects. Omega-3 fatty acids, vitamin A, and zinc were the antioxidants that reportedly improved the indirect hemolysis parameters such as hemoglobin, hematocrit, mean corpuscular volume, or red blood cells. High-dose vitamin C and E supplementation worsened hemolysis, causing increased reticulocytes, lactate dehydrogenase, indirect bilirubin, and haptoglobin. More intervention studies especially high-quality controlled randomized clinical trials are needed to investigate the effects of antioxidant nutrients in reducing hemolysis in SCD.
Topics: Anemia, Sickle Cell; Antioxidants; Erythrocytes; Hemolysis; Humans; Nutrients
PubMed: 32673671
DOI: 10.1016/j.cca.2020.07.020 -
Diabetologia Aug 2023To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death. (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death.
METHODS
This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach.
RESULTS
A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n=21 studies), HbA (53-75 mmol/mol [7-9%]: 1.18 [1.06, 1.32], n=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n=9), pre-existing heart failure (1.33 [1.21, 1.47], n=14), pre-existing liver disease (1.40 [1.17, 1.67], n=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n=2), high levels of C-reactive protein (per 5 mg/l increase: 1.07 [1.02, 1.12], n=10), aspartate aminotransferase level (per 5 U/l increase: 1.28 [1.06, 1.54], n=5), eGFR (per 10 ml/min per 1.73 m increase: 0.80 [0.71, 0.90], n=6), lactate dehydrogenase level (per 10 U/l increase: 1.03 [1.01, 1.04], n=7) and lymphocyte count (per 1×10/l increase: 0.59 [0.40, 0.86], n=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing COVID-19 vaccination status (0.32 [0.26, 0.38], n=3), pre-existing hypertension (1.23 [1.14, 1.33], n=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out.
CONCLUSIONS/INTERPRETATION
Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease.
REGISTRATION
PROSPERO registration no. CRD42020193692.
PREVIOUS VERSION
This is a living systematic review and meta-analysis. The previous version can be found at https://link.springer.com/article/10.1007/s00125-021-05458-8 FUNDING: The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD).
Topics: Male; Humans; COVID-19; SARS-CoV-2; Diabetes Mellitus; Prognosis; Phenotype; Observational Studies as Topic
PubMed: 37204441
DOI: 10.1007/s00125-023-05928-1 -
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 -
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 -
Therapeutic Advances in Hematology 2023Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and... (Review)
Review
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients.
OBJECTIVES
This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration.
DESIGN
This is a systematic review and meta-analysis.
DATA SOURCES AND METHODS
A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores.
RESULTS
Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by -1462.0 U/L (95% CI: -1735.6 to -1188.5) for treatment ⩽26 weeks and -1696.5 U/L (95% CI: -2122.7 to -1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5-2.3) and 1.9 g/dL (95% CI: 0.7-3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0-7.6) and 9.5 (95% CI: 7.0-12.0), respectively.
CONCLUSION
Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.
PubMed: 38105771
DOI: 10.1177/20406207231216080 -
PLoS Neglected Tropical Diseases Jun 2022Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients.
METHODS
The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I2). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger's test.
RESULTS
We identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMD<-0.5) and significantly (P<0.05) associated mortality: thrombin time (TT) (SMD = 1.53), viral load (SMD = 1.47), activated partial-thromboplastin time (APTT) (SMD = 1.37), aspartate aminotransferase (AST) (SMD = 1.19), lactate dehydrogenase (LDH) (SMD = 1.13), platelet count (PLT) (SMD = -0.47), monocyte percentage (MON%) (SMD = -0.47), lymphocyte percentage (LYM%) (SMD = -0.46) and albumin (ALB) (SMD = -0.43). Alanine aminotransferase, AST, creatin phosphokinase, LDH, PLT, partial-thromboplastin time and viral load contributed to the risk of dying of SFTS patients in each subgroup analyses. Sensitivity analysis demonstrated that the results above were robust.
CONCLUSIONS/SIGNIFICANCE
The abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.
Topics: Antiviral Agents; Bunyaviridae Infections; Humans; Laboratories, Clinical; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Thromboplastin; Viral Load
PubMed: 35714138
DOI: 10.1371/journal.pntd.0010489 -
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 -
Current Urology Apr 2017The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular... (Review)
Review
PURPOSE
The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular neuroendocrine tumors (TNET).
MATERIALS AND METHODS
Nine case series and sixteen case reports were identified by searching PubMed database and qualified for inclusion in this study. We added the data of one case treated in the department of urology in Habib Bourguiba Hospital in Sfax, to the published cases.
RESULTS
A total of 132 cases were collected. Median age at diagnosis was 39 years old (range 10- 83 years). The most common presenting symptom was either a testicular mass or a swelling in 38.46% of cases. Carcinoid syndrome was documented in 10.60% of patients. The clinical examination revealed a palpable mass in 44.70% of patients. This mass was painless and firm in most cases. Serum tumor markers (β-gonadotrophine chorionique humaine, α-feto protein, and lactate dehydrogenase) were within normal limits in all patients except in one case. Most testicular neuroendocrine tumors (76.52%) were primary and pure. The tumors were positive for chromogranin (100%), synaptophysin (100%) and cytokeratin (93.10%). Metastases were detected at time of diagnosis in eight cases (6.06%). The main treatment was radical orchiectomy performed in 127 patients (96.21%). The 5-year overall survival rate was 78.70% and the 5-year specific survival rate was 84.30%.
CONCLUSION
The diagnosis of testicular carcinoids is based on the immunohistochemistry study. The treatment of choice for these tumors is radical orchiectomy. Somatostatin analogues were reported to be effective in patients with carcinoid syndrome.
PubMed: 28559773
DOI: 10.1159/000447146 -
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 -
Journal of Immunology Research 2022Mycoplasma pneumoniae is a common pathogen of community-acquired pneumonia (CAP) in children. infection is usually regarded as a self-limiting disease, but in some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycoplasma pneumoniae is a common pathogen of community-acquired pneumonia (CAP) in children. infection is usually regarded as a self-limiting disease, but in some special cases, it can also develop into refractory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study is to analyze the clinical characteristics of CRP (C-reactive protein), LDH (lactate dehydrogenase), ESR (erythrocyte sedimentation rate), , neutrophils (%), lymphocytes (%), and lung consolidation in RMPP and explore their prediction results in the early stage of RMPP, which is important for early treatment.
METHODS
This systematic search was conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wangfang, and Cqvip, and the date was set until February 23, 2021. For the continuous variables, mean difference (MD) with 95% CI was adopted to evaluate CRP, LDH, ESR, D-dimer, neutrophils (%), lymphocytes (%), and the correlation between lung consolidation and RMPP.
RESULTS
20 studies including 5289 patients were included in the analysis, and the results showed that the CRP of the RMPP group (MD (95% CI): 22.29 (12.20, 32.38), < 0.001), LDH (MD (95% CI): 145.13 (78.62, 211.64), < 0.001), neutrophils (%) (MD (95% CI): 7.27 (0.31, 14.23), = 0.04), and D-dimer (MD (95% CI): 1.79 (-1.17, 4.74), = 0.24) was higher than that of the NRMPP group; the risk of lung consolidation in the RMPP group (OR (95% CI): 14.29 (4.52, 45.12), < 0.001) was higher than that in the NRMPP group, and there was no difference in ESR (MD (95% CI): 8.11 (-1.34, 17.56), = 0.09) and lymphocytes (%) (MD (95% CI): -6.27 (-12.81, 0.27), = 0.06) between the two groups.
CONCLUSION
So, the available evidence indicates that CRP, LDH, neutrophils (%), , and lung consolidation are predictive factors for RMPP.
Topics: Blood Sedimentation; C-Reactive Protein; Child; Humans; L-Lactate Dehydrogenase; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 35795531
DOI: 10.1155/2022/9227838