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Frontiers in Immunology 2023To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis.... (Meta-Analysis)
Meta-Analysis
Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts.
OBJECTIVE
To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.
METHODS
We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.
RESULTS
A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.
CONCLUSION
Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Immune Checkpoint Inhibitors; Liver Neoplasms; alpha-Fetoproteins
PubMed: 37520554
DOI: 10.3389/fimmu.2023.1215745 -
Acta Neuropathologica Communications Jul 2023Trimethylation of lysine 27 on histone 3 (H3K27me3) loss has been implicated in worse prognoses for patients with meningiomas. However, there have been challenges in... (Meta-Analysis)
Meta-Analysis Review
Trimethylation of lysine 27 on histone 3 (H3K27me3) loss has been implicated in worse prognoses for patients with meningiomas. However, there have been challenges in measuring H3K27me3 loss, quantifying its impact, and interpreting its clinical utility. We conducted a systematic review across Pubmed, Embase, and Web of Science to identify studies examining H3K27me3 loss in meningioma. Clinical, histopathological, and immunohistochemistry (IHC) characteristics were aggregated. A meta-analysis was performed using a random-effects model to assess prevalence of H3K27me3 loss and meningioma recurrence risk. Study bias was characterized using the NIH Quality Assessment Tool and funnel plots. Nine publications met inclusion criteria with a total of 2376 meningioma cases. The prevalence of H3K27me3 loss was 16% (95% CI 0.09-0.27), with higher grade tumors associated with a significantly greater proportion of loss. H3K27me3 loss was more common in patients who were male, had recurrent meningiomas, or required adjuvant radiation therapy. Patients were 1.70 times more likely to have tumor recurrence with H3K27me3 loss (95% CI 1.35-2.15). The prevalence of H3K27me3 loss in WHO grade 2 and 3 meningiomas was found to be significantly greater in tissue samples less than five years old versus tissue of all ages and when a broader definition of IHC staining loss was applied. This analysis demonstrates that H3K27me3 loss significantly associates with more aggressive meningiomas. While differences in IHC and tumor tissue age have led to heterogeneity in studying H3K27me3 loss, a robust prognostic signal is present. Our findings suggest an opportunity to improve study design and standardize tissue processing to optimize clinical viability of this epigenetic marker.
Topics: Child, Preschool; Female; Humans; Male; Biomarkers, Tumor; Histones; Meningeal Neoplasms; Meningioma; Prognosis
PubMed: 37491289
DOI: 10.1186/s40478-023-01615-9 -
Clinical Oral Investigations Dec 2023Rheumatoid arthritis (RA) is a debilitating disease where numerous pro-inflammatory cytokines have a proven role in its pathology. These cytokines are also involved in... (Review)
Review
OBJECTIVES
Rheumatoid arthritis (RA) is a debilitating disease where numerous pro-inflammatory cytokines have a proven role in its pathology. These cytokines are also involved in the pathogenesis of apical periodontitis (AP) where they have a pro-inflammatory role and induce bone resorption. Patients with RA may therefore be more prone to develop pulpal-periapical pathology (PPP). This study systematically reviewed the existing literature evaluating the association between RA and PPP.
MATERIALS AND METHODS
Studies including human participants with both RA and PPP were included. The search was performed in PubMed, Web of Science, and The Cochrane Library databases using keywords and Medical Subject Headings (MeSH) search terms. The risk of bias was assessed using Newcastle-Ottawa Quality Assessment Scale. The following parameters were extracted and analyzed by the reviewers; author, journal, year, design of the study, diagnostic criteria for periapical pathology, the association between rheumatoid arthritis and periapical pathology, and the evidence level.
RESULTS
The search identified 142 records. Inclusion criteria were as follows; studies in the English language, including human participants only, including patients with RA and PPP, cohort studies, cross-sectional studies, clinical trials, and case-control studies. According to the inclusion criteria, 5 studies were included in this systematic review. Three of the five studies reported significant association between RA and PPP.
CONCLUSIONS
Existing evidence suggests there may be an association between RA and PPP.
CLINICAL RELEVANCE
Clinicians should be aware that RA patients can be more prone to develop PPP which may result in a reduced quality of life.
Topics: Humans; Quality of Life; Cross-Sectional Studies; Arthritis, Rheumatoid; Periapical Periodontitis; Cytokines
PubMed: 37828236
DOI: 10.1007/s00784-023-05305-7 -
Diagnostics (Basel, Switzerland) Aug 2023Deep learning (DL), often called artificial intelligence (AI), has been increasingly used in Pathology thanks to the use of scanners to digitize slides which allow us to... (Review)
Review
Deep learning (DL), often called artificial intelligence (AI), has been increasingly used in Pathology thanks to the use of scanners to digitize slides which allow us to visualize them on monitors and process them with AI algorithms. Many articles have focused on DL applied to prostate cancer (PCa). This systematic review explains the DL applications and their performances for PCa in digital pathology. Article research was performed using PubMed and Embase to collect relevant articles. A Risk of Bias (RoB) was assessed with an adaptation of the QUADAS-2 tool. Out of the 77 included studies, eight focused on pre-processing tasks such as quality assessment or staining normalization. Most articles ( = 53) focused on diagnosis tasks like cancer detection or Gleason grading. Fifteen articles focused on prediction tasks, such as recurrence prediction or genomic correlations. Best performances were reached for cancer detection with an Area Under the Curve (AUC) up to 0.99 with algorithms already available for routine diagnosis. A few biases outlined by the RoB analysis are often found in these articles, such as the lack of external validation. This review was registered on PROSPERO under CRD42023418661.
PubMed: 37627935
DOI: 10.3390/diagnostics13162676 -
World Journal of Surgical Oncology Jul 2023To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging.
METHODS
PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies.
RESULTS
This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study.
CONCLUSIONS
For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.
Topics: Humans; Metformin; Neoadjuvant Therapy; Chemoradiotherapy; Rectal Neoplasms; Diabetes Mellitus; Treatment Outcome
PubMed: 37491250
DOI: 10.1186/s12957-023-03087-6 -
Knee Surgery, Sports Traumatology,... Dec 2023Implantation of mesenchymal stem cells (MSCs) is a potential cell-based modality for cartilage repair. Currently, its clinical use largely surrounds focal cartilage... (Review)
Review
Mesenchymal stem cell implantation provides short-term clinical improvement and satisfactory cartilage restoration in patients with knee osteoarthritis but the evidence is limited: a systematic review performed by the early-osteoarthritis group of ESSKA-European knee associates section.
PURPOSE
Implantation of mesenchymal stem cells (MSCs) is a potential cell-based modality for cartilage repair. Currently, its clinical use largely surrounds focal cartilage defect repair and intra-articular injections in knee osteoarthritis. The MSCs' implantation efficacy as a treatment option for osteoarthritis remains contentious. This systematic review aims to evaluate studies that focused on MSCs implantation in patients with knee OA to provide a summary of this treatment option outcomes.
METHODS
A systematic search was performed in PubMed (Medline), Scopus, Cinahl, and the Cochrane Library. Original studies investigating outcomes of MSCs implantations in patients with knee OA were included. Data on clinical outcomes using subjective scores, radiological outcomes, and second-look arthroscopy gradings were extracted.
RESULTS
Nine studies were included in this review. In all included studies, clinical outcome scores revealed significantly improved functionality and better postoperative pain scores at 2-3 years follow-up. Improved cartilage volume and quality at the lesion site was observed in five studies that included a postoperative magnetic resonance imaging assessment and studies that performed second-look arthroscopy. No major complications or tumorigenesis occurred. Outcomes were consistent in both single MSCs implantation and concurrent HTO with MSCs implantation in cases with excessive varus deformity.
CONCLUSION
According to the available literature, MSCs implantation in patients with mild to moderate knee osteoarthritis is safe and provides short-term clinical improvement and satisfactory cartilage restoration, either as a standalone procedure or combined with HTO in cases with axial deformity. However, the evidence is limited due to the high heterogeneity among studies and the insufficient number of studies including a control group and mid-term outcomes.
LEVEL OF EVIDENCE
IV.
Topics: Humans; Osteoarthritis, Knee; Cartilage, Articular; Knee Joint; Knee; Treatment Outcome; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Injections, Intra-Articular
PubMed: 37737920
DOI: 10.1007/s00167-023-07575-w -
Vaccines Nov 2023The variation in the reported vaccine safety and effectiveness could contribute to the high rates of vaccine hesitancy among the general population and healthcare... (Review)
Review
BACKGROUND
The variation in the reported vaccine safety and effectiveness could contribute to the high rates of vaccine hesitancy among the general population and healthcare workers in areas where monkeypox (mpox) is circulating. In this review, our objective was to evaluate the safety, immunogenicity, effectiveness, and efficacy of the mpox vaccines.
METHODS
An extensive search for articles across multiple databases was performed, including searching six databases (PubMed Central, PubMed Medline, Scopus, Web of Science, Cochrane, ProQuest), two pre-print databases (European PMC Preprint and MedRxiv), and Google Scholar.
RESULTS
A total of 4290 citations were retrieved from the included databases. Following the removal of duplicates and the initial screening of records, a total of 36 studies were included into the analysis. Additionally, we identified five more studies through manual searches, resulting in a total of 41 eligible articles for qualitative synthesis. The study findings revealed that mpox vaccines demonstrate the ability to generate adequate antibodies; however, their effectiveness may decrease over time, exhibiting varying safety profiles. Most of the included studies consistently reported substantial levels of effectiveness and efficacy against mpox. Interestingly, the number of vaccine doses administered was found to influence the degree of immunogenicity, subsequently impacting the overall effectiveness and efficacy of the vaccines. Furthermore, we found that smallpox vaccines exhibited a form of cross-protection against mpox.
CONCLUSIONS
Vaccines can be used to prevent mpox and effectively control its spread.
PubMed: 38006040
DOI: 10.3390/vaccines11111708 -
Dentistry Journal Dec 2023The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the... (Review)
Review
The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the PRISMA 2020 checklist guidelines, and the search was conducted using PubMed, Scopus, Lilacs, Web of science, Livivo, and EMBASE and supplemented by a gray literature search on Google Scholar and ProQuest, applying key terms relevant to the research questions. The systematic review identified 47 types of syndromes in 83 studies, and the most common was hypohidrotic ectodermal dysplasia, which was reported in 24 patients in 22 studies. Other common syndromes that reported oligodontia included Axenfeld-Rieger syndrome, Witkop's syndrome, Ellis-van Creveld syndrome, blepharocheilodontic syndrome, and oculofaciocardiodental syndrome. The X-linked mode of inheritance was the most reported (n = 13 studies), followed by the autosomal dominant (n = 13 studies). The review describes the main syndromes that may have oligodontia as a clinical sign and reinforces the need for orodental-facial examining for adequate diagnosis and treatment of the affected patients. Molecular analysis in order to better understand the occurrence of oligodontia is imperative.
PubMed: 38132417
DOI: 10.3390/dj11120279 -
EClinicalMedicine Aug 2023Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV)...
BACKGROUND
Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer.
METHODS
We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201.
FINDINGS
We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity.
INTERPRETATION
Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance.
FUNDING
There was no funding source for this study.
PubMed: 37588624
DOI: 10.1016/j.eclinm.2023.102128 -
Breast (Edinburgh, Scotland) Oct 2023Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of... (Review)
Review
OBJECTIVE
Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0-91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women.
METHODS
A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression.
RESULTS
Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20-100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1-4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk.
CONCLUSION
To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9-80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening.
Topics: Female; Humans; Carcinoma, Intraductal, Noninfiltrating; Breast Neoplasms; Disease Progression; Computer Simulation; Early Detection of Cancer; Carcinoma, Ductal, Breast
PubMed: 37541171
DOI: 10.1016/j.breast.2023.07.012