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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 -
European Stroke Journal Feb 2024Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the...
Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.
INTRODUCTION
Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM.
PATIENTS AND METHODS
A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo).
RESULTS
Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; < 0.01; = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; < 0.01; = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; < 0.01; = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; < 0.01; = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; < 0.01; = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; = 0.105; = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; < 0.01; = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; = 0.792; = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction.
DISCUSSION AND CONCLUSION
GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.
PubMed: 38400569
DOI: 10.1177/23969873241234238 -
CNS Neuroscience & Therapeutics Feb 2024Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and... (Review)
Review
BACKGROUND AND OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.
METHODS
A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.
RESULTS
A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.
CONCLUSIONS
The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.
Topics: Humans; Diffusion Tensor Imaging; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Frontotemporal Dementia; Magnetic Resonance Imaging; Hippocampus; Biomarkers; Neuropsychological Tests; Atrophy
PubMed: 38334254
DOI: 10.1111/cns.14578 -
The Journal of Maternal-fetal &... Dec 2023To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype and chromosomal microarray (CMA) analyses in fetuses with isolated increased nuchal translucency (NT) and normal fetal anatomy at the time of 11-14 weeks scan.
MATERIALS AND METHODS
Medline and Embase databases were searched. Inclusion criteria were fetuses with NT >95 percentile, normal karyotype and CMA and no associated structural anomalies at the time of the 11-14 weeks scan. The primary outcome was to estimate the incremental yield of detecting pathogenic or likely pathogenic genetic variants by WES over standard karyotype and CMA analyses in fetuses with isolated increased nuchal translucency. The secondary outcomes were the detection of a genetic variant of unknown significance. Sub-analysis according to different NT cutoffs (between 3.0 and 5.5 mm and > 5.5 mm) and considering fetuses with isolated NT in which fetal anatomy was confirmed to be normal at the anomaly scan were also performed. Random effects model meta-analyses of proportion were used to analyze the data.
RESULTS
Eight articles (324 fetuses) were included in the systematic review. Of the fetuses with negative standard karyotype and CMA analysis, the 8.07% (95% CI 5.4-11.3) had pathogenic or likely pathogenic genetic variants detected exclusively by WES. When stratifying the analysis according to NT cutoffs, genetic anomalies detected exclusively at WES analysis were found in 44.70% (95% CI 26.8-63.4) of fetuses with NT between 3.0 mm and 5.5 mm and 55.3% (95% CI 36.6-73.2) in those fetuses with NT >5.5 mm and positive WES results. The 7.84% (95% CI 1.6-18.2) had variants of unknown significance identified by WES. When considering fetuses with isolated increased NT and normal fetal anatomy at the anomaly scan, the rate of pathogenic or likely pathogenic genetic variants detected by WES was 3.87% (95% CI 1.6-7.1), while variants of unknown significance were detected in 4.27% (95% CI 2.2-7.0) of cases.
CONCLUSIONS
Pathogenic and likely pathogenic genetic variants detected by WES are present in a significant proportion of fetuses with increased NT but normal standard karyotype and CMA analysis, also when no anomalies are detected at the anomaly scan. Further large studies sharing objective protocols of imaging assessment are needed to confirm these findings and to elucidate which gene panels should be assessed in fetuses with isolated increased NT to rule out associated genetic anomalies, which may potentially impact post-natal outcomes.
Topics: Pregnancy; Female; Humans; Nuchal Translucency Measurement; Exome Sequencing; Fetus; Karyotyping; Karyotype; Prenatal Diagnosis
PubMed: 37019452
DOI: 10.1080/14767058.2023.2193285 -
Journal of Taibah University Medical... Apr 2024This research was aimed at assessing comprehension, attitudes, and perspectives regarding artificial intelligence (AI) in dentistry. The null hypothesis was a lack of... (Review)
Review
OBJECTIVES
This research was aimed at assessing comprehension, attitudes, and perspectives regarding artificial intelligence (AI) in dentistry. The null hypothesis was a lack of foundational understanding of AI in dentistry.
METHODS
This systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in May 2023. The eligibility criteria included cross-sectional studies published in English until July 2023, focusing solely on dentists or dental students. Data on AI knowledge, use, and perceptions were extracted and assessed for bias risk with the Joanna Briggs Institute checklist.
RESULTS
Of 408 publications, 22 relevant articles were identified, and 13 studies were included in the review. The average basic AI knowledge score was 58.62 % among dental students and 71.75 % among dentists. More dental students (72.01 %) than dentists (62.60 %) believed in AI's potential for advancing dentistry.
CONCLUSIONS
Thorough AI instruction in dental schools and continuing education programs for practitioners are urgently needed to maximize AI's potential benefits in dentistry. An integrated PhD program could drive revolutionary discoveries and improve patient care globally. Embracing AI with informed understanding and training will position dental professionals at the forefront of technological advancements in the field.
PubMed: 38293587
DOI: 10.1016/j.jtumed.2023.12.010 -
Frontiers in Immunology 2023The surge in the number of publications on psoriasis has posed significant challenges for researchers in effectively managing the vast amount of information. However,...
BACKGROUND
The surge in the number of publications on psoriasis has posed significant challenges for researchers in effectively managing the vast amount of information. However, due to the lack of tools to process metadata, no comprehensive bibliometric analysis has been conducted.
OBJECTIVES
This study is to evaluate the trends and current hotspots of psoriatic research from a macroscopic perspective through a bibliometric analysis assisted by machine learning based semantic analysis.
METHODS
Publications indexed under the Medical Subject Headings (MeSH) term "Psoriasis" from 2003 to 2022 were extracted from PubMed. The generative statistical algorithm latent Dirichlet allocation (LDA) was applied to identify specific topics and trends based on abstracts. The unsupervised Louvain algorithm was used to establish a network identifying relationships between topics.
RESULTS
A total of 28,178 publications were identified. The publications were derived from 176 countries, with United States, China, and Italy being the top three countries. For the term "psoriasis", 9,183 MeSH terms appeared 337,545 times. Among them, MeSH term "Severity of illness index", "Treatment outcome", "Dermatologic agents" occur most frequently. A total of 21,928 publications were included in LDA algorithm, which identified three main areas and 50 branched topics, with "Molecular pathogenesis", "Clinical trials", and "Skin inflammation" being the most increased topics. LDA networks identified "Skin inflammation" was tightly associated with "Molecular pathogenesis" and "Biological agents". "Nail psoriasis" and "Epidemiological study" have presented as new research hotspots, and attention on topics of comorbidities, including "Cardiovascular comorbidities", "Psoriatic arthritis", "Obesity" and "Psychological disorders" have increased gradually.
CONCLUSIONS
Research on psoriasis is flourishing, with molecular pathogenesis, skin inflammation, and clinical trials being the current hotspots. The strong association between skin inflammation and biologic agents indicated the effective translation between basic research and clinical application in psoriasis. Besides, nail psoriasis, epidemiological study and comorbidities of psoriasis also draw increased attention.
Topics: Humans; United States; Psoriasis; Arthritis, Psoriatic; Bibliometrics; Dermatitis; Machine Learning; Inflammation
PubMed: 37954610
DOI: 10.3389/fimmu.2023.1272080 -
F1000Research 2023This study reviews the literature on gastric metastases (GM) in terms of diagnosis, treatment, and outcomes. The goal of this study was to provide clinicians with a...
This study reviews the literature on gastric metastases (GM) in terms of diagnosis, treatment, and outcomes. The goal of this study was to provide clinicians with a reliable and beneficial source to understand gastric metastases arising from various primary tumors and to present the growing literature in an easily accessible form. Articles published in English language from implementation of MEDLINE and Cochrane databases until May 2022 were considered for the systematic review. Articles other than English language, letters to the editor, posters, and clinical images were excluded. Hematogenous and lymphogenic metastases were included whereas direct tumoral invasion and seeding were excluded. Articles and abstracts were analyzed and last selection was done after cross-referencing and by use of defined eligibility criteria. In total 1,521 publications were identified and 170 articles were finally included totaling 186 patients with GM. The median age of patients was 62 years. Gynecologic cancer was the most common cancer type causing GM (67 patients), followed by lung cancer (33 patients), renal cancer (20 patients), and melanoma (19 patients). One of the main treatment methods performed for metastasis was resection surgery (n=62), sometimes combined with chemotherapy (ChT) or immunotherapy. ChT was the other most used treatment method (n=78). Also, immunotherapy was amongst the most preferred treatment options after surgery and ChT (n=10). As 172 case reports were screened in the systematic review from different journals, heterogeneity was inevitable. Some articles missed important information such as complete follow-up or clinical information. Moreover, since all of the included articles were case reports quality assessment could not be performed. Among 172 case reports reviewed, resection surgery was performed the most and was sometimes combined with ChT and immunotherapy. Further research about what type of treatment has the best outcomes for patients with gastric metastases is needed.
Topics: Humans; Stomach Neoplasms; Female; Immunotherapy; Male; Middle Aged
PubMed: 38706640
DOI: 10.12688/f1000research.140758.1 -
Journal of Neurosurgery Dec 2023The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite literature suggesting that meningiomas are sensitive to gonadal steroid hormones. Therefore, the authors sought to collect and compare data on this topic by performing a systematic review and meta-analysis of reported studies of HR status in meningiomas.
METHODS
A MEDLINE PubMed literature review conducted for articles published between January 1, 1951, and December 31, 2020, resulted in 634 unduplicated articles concerning meningiomas and HRs. There were 114 articles that met the criteria of detailed detection protocols for progesterone receptor (PR), estrogen receptor (ER), and/or androgen receptor (AR) using immunohistochemistry (IHC) or ligand-binding (LB) assays and simultaneous reporting of HR status with at least one variable among age, sex, histology, location, grade, or recurrence. Between-study heterogeneity and risk of bias were evaluated using graphical and statistical methods. The authors performed a multilevel meta-analysis using random-effects modeling on aggregated data (n = 4447) and individual participant data (n = 1363) with subgroup results summarized as pooled effects. A mixed-effects meta-regression using individual participant data was performed to analyze independently associated variables.
RESULTS
The 114 selected articles included data for 5810 patients with 6092 tumors analyzed to determine the expression of three HRs in human meningiomas: PRs, ARs, and ERs. The proportions of HR+ meningiomas were estimated to be 0.76 (95% CI 0.72-0.80) for PR+ and 0.50 (95% CI 0.33-0.66) for AR+ meningiomas. ER+ meningioma detection varied depending on the measurement method used and was 0.06 (95% CI 0.03-0.10) with IHC and 0.11 (95% CI 0.06-0.20) with LB assays. There were associations between age and PR and ER expression that varied between male and female patients. PR+ and AR+ were more common in female patients (OR 1.84, 95% CI 1.47-2.29 for PR and OR 4.16, 95% CI 1.62-10.68 for AR). Additionally, PR+ meningiomas were enriched in skull base locations (OR 1.89, 95% CI 1.03-3.48) and meningothelial histology (OR 1.86, 95% CI 1.23-2.81). A meta-regression showed that PR+ was independently associated with age (OR 1.11 95% CI 1.09-1.13; p < 0.0001) and WHO grade I tumors (OR 8.09, 95% CI 3.55-18.44; p < 0.0001). ER+ was negatively associated with meningothelial histology (OR 0.94, 95% CI 0.86-0.98; p = 0.044) and positively associated with convexity location (OR 1.12, 95% CI 1.05-1.18; p = 0.0003).
CONCLUSIONS
The association between HRs and meningioma features has been investigated but unexplained for decades. In this study the authors demonstrated that HR status has a strong association with known meningioma features, including WHO grade, age, female sex, histology, and anatomical location. Identifying these independent associations allows for a better understanding of meningioma heterogeneity and provides a foundation for revisiting targeted hormonal therapy in meningioma on the basis of proper patient stratification according to HR status.
Topics: Humans; Male; Female; Meningioma; Meningeal Neoplasms; Immunohistochemistry; Skull Base; Receptors, Estrogen; Gonadal Steroid Hormones
PubMed: 37243565
DOI: 10.3171/2023.3.JNS221838 -
Breast (Edinburgh, Scotland) Oct 2023Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.
METHODS
We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.
RESULTS
The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years.
CONCLUSION
This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.
Topics: Aged; Humans; Female; Breast Neoplasms; Cyclin-Dependent Kinase 4; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Fulvestrant; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37198053
DOI: 10.1016/j.breast.2023.05.002 -
Nutrients Sep 2023Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, bloating, and changes in bowel habits. Various dietary factors... (Review)
Review
BACKGROUND
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, bloating, and changes in bowel habits. Various dietary factors have been implicated in the pathogenesis and management of IBS symptoms. This systematic review aims to evaluate the effects of polyphenols, minerals, fibers, and fruits on the symptoms and overall well-being of individuals with IBS.
MATERIALS AND METHODS
A comprehensive literature search was conducted in several electronic databases, including PubMed, Scopus, and Web of Science. Studies published up until July 2023 were included.
RESULTS
The selected studies varied in terms of study design, participant characteristics, intervention duration, and outcome measures. Overall, the findings suggest that dietary interventions involving polyphenols, minerals, fibers, and fruits can have a positive impact on IBS symptoms. Dietary fiber supplementation, particularly soluble fiber, has been associated with reduced bloating and enhanced stool consistency.
CONCLUSIONS
This systematic review provides evidence supporting the beneficial effects of polyphenols, minerals, fibers, and fruits in IBS patients. These dietary components hold promise as complementary approaches for managing IBS symptoms. However, due to the heterogeneity of the included studies and the limited number of high-quality randomized controlled trials, further well-designed trials are warranted to establish the optimal dosages, duration, and long-term effects of these interventions. Understanding the role of specific dietary components in IBS management may pave the way for personalized dietary recommendations and improve the quality of life for individuals suffering from this complex disorder.
Topics: Humans; Fruit; Polyphenols; Irritable Bowel Syndrome; Quality of Life; Minerals; Flatulence
PubMed: 37764853
DOI: 10.3390/nu15184070