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Translational Oncology Jun 2021Circulating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma... (Review)
Review
BACKGROUND
Circulating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma.
OBJECTIVES
To describe the clinical prognostic value of ctDNA for melanoma patients.
METHODS
Searched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22-3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98-3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19-4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77-4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48-15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36-10.33, p < 0.001).
CONCLUSION
Investigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.
PubMed: 33744725
DOI: 10.1016/j.tranon.2021.101072 -
Critical Reviews in Oncology/hematology Jul 2023Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The... (Meta-Analysis)
Meta-Analysis Review
Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.
Topics: Humans; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms
PubMed: 37210016
DOI: 10.1016/j.critrevonc.2023.104021 -
NPJ Science of Food May 2021Achieving food security is a critical challenge of the Anthropocene that may conflict with environmental and societal goals such as increased energy access. The "fuel... (Review)
Review
Achieving food security is a critical challenge of the Anthropocene that may conflict with environmental and societal goals such as increased energy access. The "fuel versus food" debate coupled with climate mitigation efforts has given rise to next-generation biofuels. Findings of this systematic review indicate just over half of the studies (56% of 224 publications) reported a negative impact of bioenergy production on food security. However, no relationship was found between bioenergy feedstocks that are edible versus inedible and food security (P value = 0.15). A strong relationship was found between bioenergy and type of food security parameter (P value < 0.001), sociodemographic index of study location (P value = 0.001), spatial scale (P value < 0.001), and temporal scale (P value = 0.017). Programs and policies focused on bioenergy and climate mitigation should monitor multiple food security parameters at various scales over the long term toward achieving diverse sustainability goals.
PubMed: 33947871
DOI: 10.1038/s41538-021-00091-6 -
Frontiers in Endocrinology 2023The diversity of clinical trajectories in diabetic kidney disease (DKD) has made blood and biochemical urine markers less precise, while renal puncture, the gold... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The diversity of clinical trajectories in diabetic kidney disease (DKD) has made blood and biochemical urine markers less precise, while renal puncture, the gold standard, is almost impossible in the assessment of diabetic kidney disease, and the value of functional magnetic resonance imaging in the evaluation of diabetic pathological alterations is increasingly recognized.
METHODS
The literature on functional magnetic resonance imaging (fMRI) for the assessment of renal alterations in diabetic kidney disease was searched in PubMed, Web of Science, Cochrane Library, and Embase databases. The search time limit is from database creation to March 10, 2023. RevMan was used to perform a meta-analysis of the main parameters of fMRIs extracted from DKD patients and healthy volunteers (HV).
RESULTS
24 publications (1550 subjects) were included in this study, using five functional MRIs with seven different parameters. The renal blood flow (RBF) values on Arterial spin labeling magnetic resonance imaging (ASL-MRI) was significantly lower in the DKD group than in the HV group. The [WMD=-99.03, 95% CI (-135.8,-62.27), <0.00001]; Diffusion tensor imaging magnetic resonance imaging (DTI-MRI) showed that the fractional anisotropy (FA) values in the DKD group were significantly lower than that in HV group [WMD=-0.02, 95%CI (-0.03,-0.01), <0.0001]. And there were no statistically significant differences in the relevant parameters in Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) or Intro-voxel incoherent movement magnetic resonance imaging (IVIM-DWI).
DISCUSSION
ASL and DWI can identify the differences between DKD and HV. DTI has a significant advantage in assessing renal cortical changes; IVIM has some value in determining early diabetic kidney disease from the cortex or medulla. We recommend combining multiple fMRI parameters to assess structural or functional changes in the kidney to make the assessment more comprehensive. We did not observe a significant risk of bias in the present study.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk, identifier CRD42023409249.
Topics: Magnetic Resonance Imaging; Diabetic Neuropathies; Diffusion Tensor Imaging; Kidney; Diabetes Mellitus
PubMed: 37484949
DOI: 10.3389/fendo.2023.1226830 -
PloS One 2022To assess the diagnostic utility of smartphone-based measurement in detecting moderate to severe obstructive sleep apnea syndrome (OSAS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the diagnostic utility of smartphone-based measurement in detecting moderate to severe obstructive sleep apnea syndrome (OSAS).
METHODS
Six databases were thoroughly reviewed. Random-effect models were used to estimate the summary sensitivity, specificity, negative predictive value, positive predictive value, diagnostic odds ratio, summary receiver operating characteristic curve and measured the areas under the curve. To assess the accuracy and precision, pooled mean difference and standard deviation of apnea hypopnea index (AHI) between smartphone and polysomnography (95% limits of agreement) across studies were calculated using the random-effects model. Study methodological quality was evaluated using the QUADAS-2 tool.
RESULTS
Eleven studies were analyzed. The smartphone diagnostic odds ratio for moderate-to-severe OSAS (apnea/hypopnea index > 15) was 57.3873 (95% confidence interval [CI]: [34.7462; 94.7815]). The area under the summary receiver operating characteristic curve was 0.917. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.9064 [0.8789; 0.9282], 0.8801 [0.8227; 0.9207], 0.9049 [0.8556; 0.9386], and 0.8844 [0.8234; 0.9263], respectively. We performed subgroup analysis based on the various OSAS detection methods (motion, sound, oximetry, and combinations thereof). Although the diagnostic odds ratios, specificities, and negative predictive values varied significantly (all p < 0.05), all methods afforded good sensitivity (> 80%). The sensitivities and positive predictive values were similar for the various methods (both p > 0.05). The mean difference with standard deviation in the AHI between smartphone and polysomnography was -0.6845 ± 1.611 events/h [-3.8426; 2.4735].
CONCLUSIONS
Smartphone could be used to screen the moderate-to-severe OSAS. The mean difference between smartphones and polysomnography AHI measurements was small, though limits of agreement was wide. Therefore, clinicians should be cautious when making clinical decisions based on these devices.
Topics: Humans; Oximetry; Polysomnography; Predictive Value of Tests; Sleep Apnea, Obstructive; Smartphone
PubMed: 35587944
DOI: 10.1371/journal.pone.0268585 -
The Cochrane Database of Systematic... Jan 2015Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by deleting (craniospinal) RT in very young children and by diminishing the dose and field to the craniospinal axis and reducing the boost volume to the tumour bed in older children.
PRIMARY OBJECTIVES
1. to determine the event-free survival/disease-free survival (EFS/DFS) and overall survival (OS) in children with medulloblastoma receiving chemotherapy as a part of their primary treatment, as compared with children not receiving chemotherapy as part of their primary treatment; 2. to determine EFS/DFS and OS in children with medulloblastoma receiving standard-dose RT without chemotherapy, as compared with children receiving reduced-dose RT with chemotherapy as their primary treatment.
SECONDARY OBJECTIVES
to determine possible adverse effects of chemotherapy and RT, including long-term adverse effects and effects on quality of life.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 7), MEDLINE/PubMed (1966 to August 2013) and EMBASE/Ovid (1980 to August 2013). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases (August 2013).
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating the above treatments in children (aged 0 to 21 years) with medulloblastoma.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction and risk of bias assessment. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. Where possible, we pooled results.
MAIN RESULTS
The search identified seven RCTs, including 1080 children, evaluating treatment including chemotherapy and treatment not including chemotherapy. The meta-analysis of EFS/DFS not including disease progression during therapy as an event in the definition showed a difference in favour of treatment including chemotherapy (hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.54 to 0.91; P value = 0.007; 2 studies; 465 children). However, not including disease progression as an event might not be optimal and the finding was not confirmed in the meta-analysis of EFS/DFS including disease progression during therapy as an event in the definition (HR 1.02; 95% CI 0.70 to 1.47; P value = 0.93; 2 studies; 300 children). Two individual studies using unclear or other definitions of EFS/DFS also showed no clear evidence of difference between treatment arms (one study with unclear definition of DFS: HR 1.67; 95% CI 0.59 to 4.71; P value = 0.34; 48 children; one study with other definition of EFS: HR 0.84; 95% CI 0.58 to 1.21; P value = 0.34; 233 children). In addition, it should be noted that in one of the studies not including disease progression as an event, the difference in DFS only reached statistical significance while the study was running, but due to late relapses in the chemotherapy arm, this significance was no longer evident with longer follow-up. There was no clear evidence of difference in OS between treatment arms (HR 1.06; 95% CI 0.67 to 1.67; P value = 0.80; 4 studies; 332 children). Out of eight reported adverse effects, of which seven were reported in one study, two (severe infections and fever/neutropenia) showed a difference in favour of treatment not including chemotherapy (severe infections: risk ratio (RR) 5.64; 95% CI 1.28 to 24.91; P value = 0.02; fever/neutropenia: RR not calculable; Fisher's exact P value = 0.01). There was no clear evidence of a difference between treatment arms for other adverse effects (acute alopecia: RR 1.00; 95% CI 0.92 to 1.08; P value = 1.00; reduction in intelligence quotient: RR 0.78; 95% CI 0.46 to 1.30; P value = 0.34; secondary malignancies: Fisher's exact P value = 0.5; haematological toxicity: RR 0.54; 95% CI 0.20 to 1.45; P value = 0.22; hepatotoxicity: Fisher's exact P value = 1.00; treatment-related mortality: RR 2.37; 95% CI 0.43 to 12.98; P value = 0.32; 3 studies). Quality of life was not evaluated. In individual studies, the results in subgroups (i.e. younger/older children and high-risk/non-high-risk children) were not univocal.The search found one RCT comparing standard-dose RT with reduced-dose RT plus chemotherapy. There was no clear evidence of a difference in EFS/DFS between groups (HR 1.54; 95% CI 0.81 to 2.94; P value = 0.19; 76 children). The RCT did not evaluate other outcomes and subgroups.The presence of bias could not be ruled out in any of the studies.
AUTHORS' CONCLUSIONS
Based on the evidence identified in this systematic review, a benefit of chemotherapy cannot be excluded, but at this moment we are unable to draw a definitive conclusion regarding treatment with or without chemotherapy. Treatment results must be viewed in the context of the complete therapy (e.g. the effect of surgery and craniospinal RT), and the different chemotherapy protocols used. This systematic review only allowed a conclusion on the concept of treatment, not on the best strategy regarding specific chemotherapeutic agents and radiation dose. Several factors complicated the interpretation of results including the long time span between studies with important changes in treatment in the meantime. 'No evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. The fact that no significant differences between treatment arms were identified could, besides the earlier mentioned reasons, also be the result of low power or too short a follow-up period. Even though RCTs are the highest level of evidence, it should be recognised that data from non-randomised studies are available, for example on the use of chemotherapy only in very young children with promising results for children without metastatic disease. We found only one RCT addressing standard-dose RT without chemotherapy versus reduced-dose RT with chemotherapy, so no definitive conclusions can be made. More high-quality research is needed.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cerebellar Neoplasms; Child; Child, Preschool; Disease-Free Survival; Humans; Infant; Infant, Newborn; Medulloblastoma; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Young Adult
PubMed: 25879092
DOI: 10.1002/14651858.CD006678.pub2 -
Frontiers in Cardiovascular Medicine 2023Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact... (Review)
Review
BACKGROUND
Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact of chemotherapeutic agents on the integrity and function of the right ventricle (RV).
OBJECTIVES
The current metanalysis compared pre- chemotherapy versus post- chemotherapy RV parameters measured on 2D echocardiography in patients receiving anthracycline and/or trastuzumab across all breast cancer patients.
METHODS
A systematic search across PubMed, EMBASE and Cochrane databases were performed from inception of the databases until November 2021 for relevant studies. We used the inverse variance method with a random effect model and DerSimonian and Laird method of Tau2 generation to calculate mean difference [MD] with 95% confidence interval [CI]. The analysis was carried out using RevMan Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
RESULTS
Fifteen studies, constituting total of 644 patients, met the inclusion criteria, with most studies having a follow up period of less than 12 months from initiation of chemotherapy. Anthracycline and/or Trastuzumab chemotherapy resulted in a statistically significant reduction in right ventricular ejection fraction (RVEF) at follow-up [MD: 2.70, 95% CI: 0.27 to 5.13, -value- 0.03, - 71%, -value < 0.05]. Treatment with Anthracycline and/or Trastuzumab chemotherapy resulted in a significant reduction in RV fractional area change (RVFAC) at follow-up [MD: 3.74, 95% CI: 1.33 to 6.15, -value < 0.01, - 68%, -value < 0.05]. RV free wall longitudinal strain (RVFWLS) was lower at baseline, while LVEF was significantly reduced at follow-up [MD: -1.00, 95% CI: -1.86 to -0.15, -value < 0.05, - 0%, -value-0.40], [MD: 4.04, 95% CI: 2.08 to 6.01, -value < 0.01, - 91%, -value < 0.05], respectively. However, treatment with Anthracycline and/or Trastuzumab chemotherapy had no statistically significant effect on Tricuspid annular plane systolic excursion (TAPSE) at follow-up [MD: 0.53, 95% CI: -0.11 to 1.17, -value-0.11, - 98%, -value < 0.05].
CONCLUSIONS
Chemotherapy with anthracyclines and trastuzumab negatively affects right ventricular function leading to decline in RVEF, RVFAC, RVFWLS and LVEF.
PubMed: 37600030
DOI: 10.3389/fcvm.2023.1103941 -
Journal of Clinical Medicine Research Aug 2020During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however,...
BACKGROUND
During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes.
METHODS
Multiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model.
RESULTS
Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance.
CONCLUSIONS
HCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs.
PubMed: 32849936
DOI: 10.14740/jocmr4233 -
Cancer Medicine Dec 2020Gastric cancer is the third leading cause of cancer-related deaths worldwide. Novel biomarkers circRNAs can play an important role in the development of gastric cancer... (Meta-Analysis)
Meta-Analysis
Gastric cancer is the third leading cause of cancer-related deaths worldwide. Novel biomarkers circRNAs can play an important role in the development of gastric cancer as oncogenes or tumor suppressor genes. The purpose of this study was to clarify the relationship between the abnormal expression of multiple circRNAs and their prognostic value in gastric cancer patients through a meta-analysis. We researched articles reporting the relationship between circRNAs and the prognosis of gastric cancer published in PubMed, Cochrane, Embase, Web of Science, Wanfang, CNKI, and VIP databases before 31 December 2019. Thirty-five articles were selected for the meta-analysis, involving 3135 gastric cancer patients. The total HR values (95% CI) of OS and DFS related to highly expressed circRNAs that indicated worse prognosis were 1.83 (1.64-2.03; p < 0.001) and 1.66 (1.33-2.07; p < 0.001), respectively. The total HR (95% CI) of OS and DFS related to highly expressed circRNAs that indicated better prognosis was 0.54 (0.45-0.66; p < 0.001) and 0.58 (0.43-0.78; p < 0.001), respectively. Two panels of five circRNAs predicted a more considerable HR value (circ_0009910, hsa_circ_0000467, hsa_circ_0065149, hsa_circ_0081143, and circDLST; and circSMARCA5, circLMTK2, hsa_circ_0001017, hsa_circ_0061276, and circ-KIAA1244). The results of the meta-analysis were 2.63 (2.08-3.33; p < 0.001) and 0.39 (0.27-0.59; p < 0.001) for OS, respectively. The two panels of dysregulated circRNAs can be considered as more suitable potential prognostic tumor biomarkers in patients with gastric cancer because of their larger HR values.
Topics: Biomarkers, Tumor; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Risk Assessment; Risk Factors; Stomach Neoplasms; Time Factors
PubMed: 33108710
DOI: 10.1002/cam4.3497 -
La Radiologia Medica May 2023The aim of the present systematic review and meta-analysis is to assess the accuracy of automated landmarking using deep learning in comparison with manual tracing for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of the present systematic review and meta-analysis is to assess the accuracy of automated landmarking using deep learning in comparison with manual tracing for cephalometric analysis of 3D medical images.
METHODS
PubMed/Medline, IEEE Xplore, Scopus and ArXiv electronic databases were searched. Selection criteria were: ex vivo and in vivo volumetric data images suitable for 3D landmarking (Problem), a minimum of five automated landmarking performed by deep learning method (Intervention), manual landmarking (Comparison), and mean accuracy, in mm, between manual and automated landmarking (Outcome). QUADAS-2 was adapted for quality analysis. Meta-analysis was performed on studies that reported as outcome mean values and standard deviation of the difference (error) between manual and automated landmarking. Linear regression plots were used to analyze correlations between mean accuracy and year of publication.
RESULTS
The initial electronic screening yielded 252 papers published between 2020 and 2022. A total of 15 studies were included for the qualitative synthesis, whereas 11 studies were used for the meta-analysis. Overall random effect model revealed a mean value of 2.44 mm, with a high heterogeneity (I = 98.13%, τ = 1.018, p-value < 0.001); risk of bias was high due to the presence of issues for several domains per study. Meta-regression indicated a significant relation between mean error and year of publication (p value = 0.012).
CONCLUSION
Deep learning algorithms showed an excellent accuracy for automated 3D cephalometric landmarking. In the last two years promising algorithms have been developed and improvements in landmarks annotation accuracy have been done.
Topics: Humans; Deep Learning; Anatomic Landmarks; Reproducibility of Results; Cephalometry; Imaging, Three-Dimensional; Algorithms
PubMed: 37093337
DOI: 10.1007/s11547-023-01629-2