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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 -
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 -
Critical Care Explorations May 2021This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019... (Review)
Review
UNLABELLED
This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019 patients and to review the manifestations of coronavirus disease 2019-associated thrombotic pathologies reported in the recent literature.
DATA SOURCES
PubMed, Excerpta Medica Database, and Cochrane library between December 1, 2019, and August 26, 2020.
STUDY SELECTION
Investigators screened 360 unique references, retrieved published autopsy series, and report on the postmortem histopathologic information on patients who had died of coronavirus disease 2019.
DATA EXTRACTION
Investigators independently abstracted all available data including study design, participant demographics, key histopathologic findings, disease severity markers, duration of hospital stay, and cause of death.
DATA SYNTHESIS
From the 65 eligible studies, 691 total completed autopsies were included in evidence synthesis. Histopathologic evaluation of the lungs revealed presence of diffuse alveolar damage in 323 of 443 patients and pulmonary microthrombi in 242 of 326 patients. Deep venous thrombosis and pulmonary embolism were found in 41% and ~15%, respectively, of the cadavers examined for thromboembolic events. d-dimer levels were generally higher in patients with severe clinical course of coronavirus disease 2019. Plasma levels of ferritin, lactate dehydrogenase, interleukin-6, and C-reactive protein were higher in nonsurvivors when compared with survivors. Overall, microthrombi and extensive angiogenesis of lung vasculature were the most common pathologic findings in the lungs and microthrombi in most of the assessed organ-tissue.
CONCLUSIONS
Diffuse alveolar damage was the most predominant feature in the lungs of coronavirus disease 2019 patients who underwent postmortem assessment. Widespread pulmonary microthrombosis and extensive pulmonary angiogenesis, in addition to frequent pulmonary and extrapulmonary microthrombotic and thromboembolic findings in patients with coronavirus disease 2019, appear to be consistent with the disease-specific hypercoagulability. Further discovery efforts in assessing the link between coronavirus disease 2019, hypercoagulable state, and immunothrombosis are warranted. In the interim, increased attention to anticoagulant treatment approaches in coronavirus disease 2019 patients is needed.
PubMed: 34036278
DOI: 10.1097/CCE.0000000000000427 -
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 -
Journal of Pediatric Hematology/oncology Aug 2021Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients with PNH.
METHODS
PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for prospective interventional studies treating PNH with eculizumab. The primary outcome was the change in lactate dehydrogenase (LDH) levels, whereas secondary outcomes included the change in hemoglobin (Hb) levels, transfusion rates, and adverse drug events.
RESULTS
Patients (n=235) from 6 studies were included in this meta-analysis. LDH and Hb levels and transfusion rates decreased significantly at 12, 26 weeks, 12, 15, and >15 months. The most frequent adverse events included nasopharyngitis (effect size [ES]: 0.53; 95% confidence intervals [CI]: 0.47 to 0.60; P=0.00), headache (ES: 0.47; 95% CI: 0.25 to 0.69; P=0.00), upper respiratory tract infection (ES: 0.37; 95% CI: 0.27 to 0.46; P=0.00), nausea (ES: 0.31; 95% CI: 0.24 to 0.38; P=0.00), fatigue, diarrhea, cough, pyrexia, abdominal pain, pain in extremities, and contusion.
CONCLUSION
Eculizumab is an effective and well-tolerated treatment for patients with PNH. It is effective at decreasing LDH levels and transfusion rates while increasing Hb levels. Further studies are needed to explore the safety of eculizumab.
Topics: Antibodies, Monoclonal, Humanized; Complement Inactivating Agents; Hemoglobinuria, Paroxysmal; Humans; L-Lactate Dehydrogenase; Treatment Outcome
PubMed: 33902068
DOI: 10.1097/MPH.0000000000002178 -
Obstetrics & Gynecology Science Mar 2021The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical...
The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.
PubMed: 33499580
DOI: 10.5468/ogs.20174 -
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 -
Infectious Diseases and Therapy Sep 2020The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and... (Review)
Review
BACKGROUND
The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged.
OBJECTIVES
We aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information.
SOURCES
A PubMed search was conducted on 1 June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data were extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes.
CONTENT
Data from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity, and an association was observed in eight (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity.
IMPLICATIONS
Data suggest that lower Ct values may be associated with worse outcomes and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.
PubMed: 32725536
DOI: 10.1007/s40121-020-00324-3 -
Frontiers in Pharmacology 2022This study aimed to evaluate the intervention effect of curcumin in myocardial infarction rodent models. A systematic retrieval of relevant studies on curcumin...
This study aimed to evaluate the intervention effect of curcumin in myocardial infarction rodent models. A systematic retrieval of relevant studies on curcumin intervention in rats or mice myocardial infarction models was conducted, and the data were extracted. The outcome indicators included biochemical blood indicators, such as creatine kinase (CK), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA), lactate dehydrogenase (LDH) and superoxide dismutase (SOD), as well as cardiac tissue structure indicators, such as left ventricular weight to body weight ratio (LVW/BW), apoptosis index, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), and myocardial infarction area, and hemodynamic indexes, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), maximum rate of left ventricular pressure rise (+dp/dtmax), and maximum rate of left ventricular pressure decline (-dp/dtmax). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool. A total of 24 studies were included in the meta-analysis. The quality assessment of included studies revealed that the evidence was low quality and none of studies was judged as having a low risk of bias across all domains. The results revealed that curcumin could reduce CK-MB, CK, LDH, and MDA levels. They also revealed that it could lower SBP, DBP, LVEDP, LVW/BW, apoptosis index, LVEDD, LVESD, and myocardial infarction area and increase LVEF, LVFS, +dp/dtmax, and-dp/dtmax. However, it had no significant impact on the heart rate and the levels of SOD in the models. Curcumin alleviates myocardial injury and oxidative stress in myocardial infarction rodent models in terms of blood biochemistry indicators, improves the diastolic and systolic capacity of the ventricle in terms of hemodynamic indexes, and reduces the necrosis and apoptosis of cardiomyocytes in terms of tissue structure. The methodological quality of the studies was low and additional research is warranted.
PubMed: 36330084
DOI: 10.3389/fphar.2022.999386