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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 -
Clinical Ophthalmology (Auckland, N.Z.) 2022This study aims to identify the available literature describing the utilization of artificial intelligence (AI) as a clinical tool in uveal diseases. (Review)
Review
PURPOSE
This study aims to identify the available literature describing the utilization of artificial intelligence (AI) as a clinical tool in uveal diseases.
METHODS
A comprehensive literature search was conducted in 5 electronic databases, finding studies relating to AI and uveal diseases.
RESULTS
After screening 10,258 studies,18 studies met the inclusion criteria. Uveal melanoma (44%) and uveitis (56%) were the two uveal diseases examined. Ten studies (56%) used complex AI, while 13 studies (72%) used regression methods. Lactate dehydrogenase (LDH), found in 50% of studies concerning uveal melanoma, was the only biomarker that overlapped in multiple studies. However, 94% of studies highlighted that the biomarkers of interest were significant.
CONCLUSION
This study highlights the value of using complex and simple AI tools as a clinical tool in uveal diseases. Particularly, complex AI methods can be used to weigh the merit of significant biomarkers, such as LDH, in order to create staging tools and predict treatment outcomes.
PubMed: 36065357
DOI: 10.2147/OPTH.S377358 -
Asian Pacific Journal of Cancer... Aug 2022Oral cancer is often preceded by Potentially Malignant Disorders (PMDs) and important role of biochemical markers for early diagnosis has been well documented; however,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral cancer is often preceded by Potentially Malignant Disorders (PMDs) and important role of biochemical markers for early diagnosis has been well documented; however, there is limited evidence of Serum lactate dehydrogenase (SLDH) as an effective biochemical marker in diagnosis of PMDs. The present meta-analysis was conducted to assess if serum LDH can be a used as standard biomarker for PMDs and consequently aid in diagnosis of oral cancer.
METHODS
A comprehensive search was conducted in Medline, Scopus, Web of Science, EBSCO host, Cochrane databases and Google Scholar for studies evaluating estimation of SLDH in PMDs. Search strategy included all types of studies evaluating level of SLDH in patients with PMDs. PRISMA guidelines were followed for the meta-analysis. Fixed-effects model was used to assess the mean differences in SLDH levels between healthy controls and PMDs.
RESULTS
A total number of nine studies were included in meta-analysis after screening for inclusion and exclusion criteria. Potentially malignant disorder was significantly associated with increased serum LDH level compared to healthy controls (pooled SMD: 1.83 (95% CI, 1.52, 2.15) (P < 0.00001; Subgroup analysis of OSMF (Oral Submucous Fibrosis) studies showed significant association with increased serum LDH level compared to healthy controls (pooled SMD: 2.57 (95% CI, 2.16, 2.98; P < 0.00001). Sensitivity analysis for the five studies reflected a significant reduction in I2 values to 24 % (P=0.26). Funnel plots were derived for any evidence of publication bias among the studies.
CONCLUSION
Meta-analysis suggests that SLDH is increased in potentially malignant disorders compared to healthy controls. The results of this metanalysis should encourage use of SLDH as a biomarker in diagnosis of PMDs.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Humans; Lactate Dehydrogenases; Mouth Neoplasms; Oral Submucous Fibrosis
PubMed: 36037107
DOI: 10.31557/APJCP.2022.23.8.2553 -
Biofouling Aug 2022This study aimed at performing a systematic review of the literature on the effects of epigallocatechin-3-gallate (EGCG) on planktonic cultures and biofilms. The...
This study aimed at performing a systematic review of the literature on the effects of epigallocatechin-3-gallate (EGCG) on planktonic cultures and biofilms. The selected references demonstrated that EGCG suppresses acid production by inhibiting the activity of enzymes such as lactate dehydrogenase and FIF0-ATPase. Regarding virulence factors, one study reported a reduction in soluble and insoluble polysaccharide synthesis, another demonstrated that EGCG inhibited GTase activity, and another showed effects of EGCG on the expression of B, C, and D. The effects of EGCG on biofilms were reported only by 2 of the selected studies. Moreover, high variability in effective concentrations and microbial assessment methods were observed. The literature suggests that EGCG has effects against planktonic cells viability and virulence factors. However, the literature lacks studies with appropriate biofilm models to evaluate the precise effectiveness of EGCG against biofilms.
Topics: Adenosine Triphosphatases; Biofilms; Catechin; Lactate Dehydrogenases; Plankton; Polysaccharides; Streptococcus mutans; Tea; Virulence Factors
PubMed: 36017657
DOI: 10.1080/08927014.2022.2116320 -
Frontiers in Oncology 2022Hyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs)....
INTRODUCTION
Hyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed.
METHODS
Clinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed R software (y -40v4.0.2).
RESULTS
Forty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%-15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types ( = .0248) and gender ratio ( = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, <.05). High lactate dehydrogenase (LDH) level (OR = 1.51, = .01), metastatic sites >2 (OR = 2.38, <.0001), Eastern Cooperative Oncology Group Performance Score ≥2 (OR = 1.47, = .02), and liver metastasis (OR = 3.06, <.0001) indicate higher risk of HPD.
CONCLUSIONS
The pooled incidence of HPD was less than 15%, and HNC had the highest incidence of HPD. LDH and PD-L1 are remarkable biomarkers for prediction of HPD in future medical practice.
PubMed: 35992878
DOI: 10.3389/fonc.2022.843707 -
Frontiers in Immunology 2022A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to...
AIMS AND BACKGROUND
A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models.
METHODS
A systematic search for analyses of PPK models of eleven anti-PD-1 mAbs on the market that were carried out in humans was conducted using PubMed, Embase, and the Cochrane Library. The search covered the period from the inception of the databases to April 2022.
RESULTS
Currently, there are fourteen analyses on PPK models of anti-PD-1 mAbs summarized in this review, including seven models that refer to nivolumab, four referring to pembrolizumab, one referring to cemiplimab, one referring to camrelizumab, and one referred to dostarlimab. Most analyses described the pharmacokinetics of anti-PD-1 mAbs with a two-compartment model with time-varying clearance (CL) and a sigmoidal maximum effect. The estimated CL and volume of distribution in the central (V) ranged from 0.179 to 0.290 L/day and 2.98 to 4.46 L, respectively. The median (range) of interindividual variability (IIV) for CL and V was 30.9% (8.7%-50.8%) and 29.0% (4.32%-40.7%), respectively. The commonly identified significant covariates were body weight (BW) on CL and V, and albumin (ALB), tumor type, sex, and performance status (PS) on CL. Other less assessed significant covariates included lactate dehydrogenase (LDH), immunoglobulin G (IgG), ipilimumab coadministration (IPICO) on CL, and body mass index (BMI), malignant pleural mesothelioma (MESO) on V.
CONCLUSION
This review provides detailed information about the characteristics of PPK models of anti-PD-1 mAbs, the effects of covariates on PK parameters, and the current status of the application of the models. ALB, BW, specific tumor type, sex, and PS should be considered for the future development of the PPK model of anti-PD-1 mAbs. Other potential covariates that were assessed less frequently but still have significance (e.g., LDH, IgG, and IPICO) should not be ignored. Thus, further research and thorough investigation are needed to assess new or potential covariates, which will pave the way for personalized anti-PD-1 mAbs therapy.
Topics: Antibodies, Monoclonal, Humanized; Body Weight; Humans; Immunoglobulin G; Ipilimumab; Neoplasms; Nivolumab
PubMed: 35983041
DOI: 10.3389/fimmu.2022.871372 -
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 -
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 -
Research and Practice in Thrombosis and... Jul 2022Pegcetacoplan, a pegylated penta-decapeptide, targets complement C3 to control both intravascular and extravascular hemolysis. This systematic review aims to study the...
INTRODUCTION
Pegcetacoplan, a pegylated penta-decapeptide, targets complement C3 to control both intravascular and extravascular hemolysis. This systematic review aims to study the efficacy and safety of pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH).
METHODS
We performed a comprehensive and systematic literature search for all studies on PubMed, Google Scholar, Cochrane Library, and clinicaltrials.gov. The studies were searched using keywords "paroxysmal nocturnal hemoglobinuria" or "PNH," "Pegcetacoplan" or "Empaveli." The primary outcomes included change in hemoglobin level, transfusion independence, absolute reticulocyte count, and lactate dehydrogenase (LDH) level after pegcetacoplan therapy. The safety outcomes included the proportion of deaths and adverse effects.
RESULTS
We included a total of three studies. The total number of patients with PNH was112. 59.83% were female. In the PADDOCK study and study by Hillmen et al., the average increase in hemoglobin was 3.68 g/L and 2.37 g/L, respectively. In the study by de Castro et al., the hemoglobin level increased from below the lower limit of normal and stayed in the normal range (11.1-15.9 g/L). Absolute reticulocyte count and LDH levels decreased in all patients receiving pegcetacoplan. In the study by de Castro et al., LDH level remained stable, and within <1.5× upper limit of normal, whereas in the study by Hillman, the mean change of LDH from baseline was -15 ± 43 U/L. Two of six, seven of 23, and seven of 41 patients reported adverse events in the study by de Castro et al., PADDOCK, and Hillmen et al., respectively.
CONCLUSION
Pegcetacoplan effectively improves hemoglobin level and transfusion requirements in patients with PNH, including those unresponsive to eculizumab.
PubMed: 35949886
DOI: 10.1002/rth2.12781 -
Frontiers in Oncology 2022The Lung Immune Prognostic Index (LIPI) combines the lactate dehydrogenase (LDH) level and the derived neutrophil-to-lymphocyte ratio (dNLR). A lot of studies have shown...
The Predictive Value of Pretreatment Lactate Dehydrogenase and Derived Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Patients Treated With PD-1/PD-L1 Inhibitors: A Meta-Analysis.
BACKGROUND
The Lung Immune Prognostic Index (LIPI) combines the lactate dehydrogenase (LDH) level and the derived neutrophil-to-lymphocyte ratio (dNLR). A lot of studies have shown that LDH and dNLR are associated with the prognosis of advanced non-small cell lung cancer (NSCLC) in patients treated with programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. However, previous results were inconsistent, and the conclusions remain unclear. This meta-analysis aimed to investigate the predictive value of pretreatment LDH and dNLR for NSCLC progression in patients treated with PD-1/PD-L1 inhibitors.
METHODS
PubMed, Embase, and the Cochrane Library were searched by two researchers independently for related literature before March 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) were extracted to assess the predictive value of LDH and dNLR. STATA 15. 0 was used to perform the meta-analysis.
RESULTS
A total of 3,429 patients from 26 studies were included in this meta-analysis. The results revealed that high pretreatment LDH was related to poor OS (HR = 1.19, 95%CI = 1.11-1.24, < 0.001), but not closely related to poor PFS (HR = 1.02, 95%CI = 1.00-1.04, = 0.023 < 0.05). The pooled results for dNLR suggested that high pretreatment dNLR was related to poor OS (HR = 1.55, 95%CI = 1.33-1.80, < 0.001) and PFS (HR = 1.33, 95%CI = 1.16-1.54, < 0.001).
CONCLUSION
Both pretreatment LDH and dNLR have the potential to serve as peripheral blood biomarkers for patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors. However, more studies on LDH are needed to evaluate its predictive value for PFS in patients with NSCLC.
PubMed: 35924149
DOI: 10.3389/fonc.2022.791496