-
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 -
Cancers Jan 2022The platelet-to-lymphocyte ratio (PLR), an inflammatory parameter, has shown prognostic value in several malignancies. The aim of this meta-analysis was to determine the... (Review)
Review
The platelet-to-lymphocyte ratio (PLR), an inflammatory parameter, has shown prognostic value in several malignancies. The aim of this meta-analysis was to determine the impact of pretreatment PLR on the oncological outcome in patients with cholangiocarcinoma (CCA). A systematic literature search has been carried out in the PubMed and Google Scholar databases for pertinent papers published between January 2000 and August 2021. Within a random-effects model, the pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to investigate the relationships among the PLR, overall survival (OS), and disease-free survival (DFS). Subgroup analysis, sensitivity analysis, and publication bias were also conducted to further evaluate the relationship. A total of 20 articles comprising 5429 patients were included in this meta-analysis. Overall, the pooled outcomes revealed that a high PLR before treatment is associated with impaired OS (HR = 1.14; 95% CI = 1.06-1.24; < 0.01) and DFS (HR = 1.57; 95% CI = 1.19-2.07; < 0.01). Subgroup analysis revealed that this association is not influenced by the treatment modality (surgical vs. non-surgical), PLR cut-off values, or sample size of the included studies. An elevated pretreatment PLR is prognostic for the OS and DFS of CCA patients. More high-quality studies are required to investigate the pathophysiological basis of the observation and the prognostic value of the PLR in clinical management as well as for patient selection.
PubMed: 35053599
DOI: 10.3390/cancers14020438 -
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 -
The Indian Journal of Medical Research Jul 2021In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the... (Review)
Review
BACKGROUND & OBJECTIVES
In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD.
METHODS
A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test.
RESULTS
A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye [conjunctival limbal autograft (CLAU)], allograft from a cadaver/live donor [keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL)] and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent [95% confidence interval (CI), 41.75-93.36; I=83.5%, P=0.002]. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group.
INTERPRETATION & CONCLUSIONS
The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.
Topics: Corneal Diseases; Humans; Limbus Corneae; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Stem Cell Transplantation; Stem Cells; Transplantation, Autologous
PubMed: 34782530
DOI: 10.4103/ijmr.IJMR_1139_18 -
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 -
Journal of Applied Physiology... Feb 2022Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving,... (Review)
Review
Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving, there is also the effect of apnea. Few studies have published blood gas data in underwater or hyperbaric environments: this review summarizes the available literature and was used to test the hypothesis that arterial Po under hyperbaric conditions can be predicted from blood gas measurement at 1 atmosphere assuming a constant arterial/alveolar Po ratio (a:A). A systematic search was performed on traditional sources including arterial blood gases obtained on humans in hyperbaric or underwater environments. The a:A was calculated at 1 atmosphere absolute (ATA). For each condition, predicted arterial partial pressure of oxygen ([Formula: see text]) at pressure was calculated using the 1 ATA a:A, and the measured [Formula: see text] was plotted against the predicted value with Spearman correlation coefficients. Of 3,640 records reviewed, 30 studies were included: 25 were reports describing values obtained in hyperbaric chambers, and the remaining were collected while underwater. Increased inspired O at pressure resulted in increased [Formula: see text], although underlying lung disease in patients treated with hyperbaric oxygen attenuated the rise. [Formula: see text] generally increased only slightly. In breath-hold divers, hyperoxemia generally occurred at maximum depth, with hypoxemia after surfacing. The a:A adequately predicted the [Formula: see text] under various conditions: dry ( = 0.993, < 0.0001), rest versus exercise ( = 0.999, < 0.0001), and breathing mixtures ( = 0.995, < 0.0001). In conclusion, pulmonary oxygenation under hyperbaric conditions can be reliably and accurately predicted from 1 ATA a:A measurements.
Topics: Blood Gas Analysis; Diving; Humans; Hyperbaric Oxygenation; Oxygen; Partial Pressure; Pulmonary Gas Exchange
PubMed: 34941439
DOI: 10.1152/japplphysiol.00569.2021 -
Frontiers in Oncology 2022The pan-immune-inflammation value (PIV) has been reported as a novel prognostic biomarker in multiple malignancies. The aim of this study is to investigate the... (Review)
Review
BACKGROUND
The pan-immune-inflammation value (PIV) has been reported as a novel prognostic biomarker in multiple malignancies. The aim of this study is to investigate the prognostic value of the PIV in patients with colorectal cancer.
METHODS
We comprehensively searched electronic databases including PubMed, Embase and Web of Science up to August 2022. The endpoints were survival outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) for survival data were collected for analysis.
RESULTS
Six studies including 1879 participants were included. A significant heterogeneity in the PIV cut-off value among studies was observed. The combined results indicated that patients in the high baseline PIV group had a worse overall survival (HR=2.09; 95%CI: 1.67-2.61; P<0.0001; I 7%) and progression-free survival (HR=1.82; 95%CI: 1.49-2.22; P<0.0001; I 15%). In addition, early PIV increase after treatment initiation was significantly associated with decreased overall survival (HR=1.79; 95%CI: 1.13-2.93; P=0.01; I 26%), and a trend toward poor progression-free survival (HR=2.00; 95%CI: 0.90-4.41; P=0.09; I 70%).
CONCLUSION
Based on existing evidence, the PIV could act as a valuable prognostic index in patients with colorectal cancer. However, the heterogeneity in the PIV cut-off value among studies should be considered when interpreting these findings.
PubMed: 36620576
DOI: 10.3389/fonc.2022.1036890 -
Neurosurgical Review Jun 2022Elevated intracranial pressure (ICP) with reduced cerebral perfusion pressure is a well-known cause of secondary brain injury. Previously, there have been some reports... (Meta-Analysis)
Meta-Analysis Review
Elevated intracranial pressure (ICP) with reduced cerebral perfusion pressure is a well-known cause of secondary brain injury. Previously, there have been some reports describing different supra- and infratentorial ICP measurements depending on the location of the mass effect. Therefore, we aimed to perform a systematic review and meta-analysis to clarify the issue of optimal ICP monitoring in the infratentorial mass lesion. A literature search of electronic databases (PUBMED, EMBASE) was performed from January 1969 until February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Two assessors are independently screened for eligible studies reporting the use of simultaneous ICP monitoring in the supra- and infratentorial compartments. For quality assessment of those studies, the New Castle Ottawa Scale was used. The primary outcome was to evaluate the value of supra- and infratentorial ICP measurement, and the secondary outcome was to determine the time threshold until equalization of both values. Current evidence surrounding infratentorial ICP measurement was found to be low to very low quality according to New Castle Ottawa Scale. Eight studies were included in the systematic review, four of them containing human subjects encompassing 27 patients with infratentorial pathology. The pooled data demonstrated significantly higher infratentorial ICP values than supratentorial ICP values 12 h after onset (p < 0.05, 95% CI 3.82-5.38) up to 24 h after onset (p < 0.05; CI 1.14-3.98). After 48-72 h, both ICP measurements equilibrated showing no significant difference. Further, four studies containing 26 pigs and eight dogs showed a simultaneous increase of supra- and infratentorial ICP value according to the increase of supratentorial mass volume; however, there was a significant difference towards lower ICP in the infratentorial compartment compared to the supratentorial compartment. The transtentorial gradient leads to a significant discrepancy between supra- and infratentorial ICP monitoring. Therefore, infratentorial ICP monitoring is warranted in case of posterior fossa lesions for at least 48 h.
Topics: Animals; Cerebrovascular Circulation; Dogs; Humans; Intracranial Hypertension; Intracranial Pressure; Monitoring, Physiologic; Skull; Swine
PubMed: 35118578
DOI: 10.1007/s10143-022-01746-y -
Frontiers in Immunology 2023Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint inhibitor (ICI) therapy. Nevertheless, the existing findings remain contentious.
METHODS
A comprehensive search of literature was conducted in databases including PubMed, Embase, Web of Science, and the Cochrane Library, spanning from the inception of each database to August 30, 2023 to collect studies exploring the interplay between LMR and clinical outcomes. Eligible studies were selected following predefined inclusion and exclusion criteria. Primary outcomes encompassed progression-free survival (PFS) and overall survival (OS), which were estimated using hazard ratios (HR) and corresponding 95% confidence intervals (CI).
RESULTS
Our analysis incorporated eight cohort studies, involving 815 patients. Aggregate data revealed associations between an elevated LMR at baseline and prolonged PFS (HR=0.58; 95% CI: 0.47-0.71, p<0.00001) and improved OS (HR=0.51, 95% CI: 0.33-0.79; p=0.003). Furthermore, LMR exhibited a favorable association with PFS after treatment (HR=0.48; 95% CI: 0.29-0.79; p= 0.004), while such a correlation was not evident in the OS analysis. Importantly, a high level of LMR was associated with prolonged PFS across varying sample sizes, follow-up duration, treatment combinations, line of therapy, and cut-off values.
CONCLUSION
A high pre-treatment LMR is associated with improved OS and PFS in GC patients treated with ICIs. LMR emerges as a potent biomarker for prognostic assessment in these patients, offering valuable insights for informed treatment decisions within the domain of GC immunotherapy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42021228512.
Topics: Humans; Prognosis; Monocytes; Immune Checkpoint Inhibitors; Stomach Neoplasms; Lymphocytes
PubMed: 38090560
DOI: 10.3389/fimmu.2023.1321584 -
Infectious Agents and Cancer 2017Literature data suggest that multi-parametric Magnetic Resonance Imaging (MRI), including morphologic T2-weigthed images (T2-MRI) and functional approaches such as... (Review)
Review
BACKGROUND
Literature data suggest that multi-parametric Magnetic Resonance Imaging (MRI), including morphologic T2-weigthed images (T2-MRI) and functional approaches such as Dynamic Contrast Enhanced-MRI (DCE-MRI), Diffusion Weighted Imaging (DWI) and Magnetic Resonance Spectroscopic Imaging (MRSI), give an added value in the prostate cancer localization and local staging.
METHODS
We performed a systematic review of literature about the role and the potentiality of morphological and functional MRI in prostate cancer, also in a multimodal / multiparametric approach, and we reported the diagnostic accuracy results for different imaging modalities and for different MR coil settings: endorectal coil (ERC) and phased array coil (PAC). Forest plots and receiver operating characteristic curves were performed. Risk of bias and the applicability at study level were calculated.
RESULTS
Thirty three papers were identified for the systematic review. Sensitivity and specificity values were, respectively, for T2-MRI of 75% and of 60%, for DCE-MRI of 80% and of 72%, for MRSI of 89% and of 69%, for combined T2-MRI and DCE-MRI of 87% and of 46%, for combined T2-MRI and MRSI of 79% and of 57%, for combined T2-MRI, DWI and DCE-MRI of 81% and of 84%, and for combined MRSI and DCE-MRI of 83% and of 83%. For MRI studies performed with ERC we obtained a pooled sensitivity and specificity of 81% and of 66% while the pooled values for MRI studies performed with PAC were of 78% and of 64%, respectively (p>0.05 at McNemar test). No studies were excluded from the analysis based on the quality assessment.
CONCLUSIONS
ERC use yielded no additional benefit in terms of prostate cancer detection accuracy compared to multi-channel PAC use (71% versus 68%) while the use of additional functional imaging techniques (DCE-MRI, DWI and MRSI) in a multiparametric MRI protocol improves the accuracy of prostate cancer detection allowing both the early cure and the guidance of biopsy.
PubMed: 29093748
DOI: 10.1186/s13027-017-0168-z