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International Journal of Nanomedicine 2022The recent advancements in hybrid positron emission tomography-magnetic resonance imaging systems (PET/MRI) have brought massive value in the investigation of disease... (Review)
Review
The recent advancements in hybrid positron emission tomography-magnetic resonance imaging systems (PET/MRI) have brought massive value in the investigation of disease processes, in the development of novel treatments, in the monitoring of both therapy response and disease progression, and, not least, in the introduction of new multidisciplinary molecular imaging approaches. While offering potential advantages over PET/CT, the hybrid PET/MRI proved to improve both the image quality and lesion detectability. In particular, it showed to be an effective tool for the study of metabolic information about lesions and pathological conditions affecting the brain, from a better tumor characterization to the analysis of metabolic brain networks. Based on the PRISMA guidelines, this work presents a systematic review on PET/MRI in basic research and clinical differential diagnosis on brain oncology and neurodegenerative disorders. The analysis includes literature works and clinical case studies, with a specific focus on the use of PET tracers and MRI contrast agents, which are usually employed to perform hybrid PET/MRI studies of brain tumors. A systematic literature search for original diagnostic studies is performed using PubMed/MEDLINE, Scopus and Web of Science. Patients, study, and imaging characteristics were extracted from the selected articles. The analysis included acquired data pooling, heterogeneity testing, sensitivity analyses, used tracers, and reported patient outcomes. Our analysis shows that, while PET/MRI for the brain is a promising diagnostic method for early diagnosis, staging and recurrence in patients with brain diseases, a better definition of the role of tracers and imaging agents in both clinical and preclinical hybrid PET/MRI applications is needed and further efforts should be devoted to the standardization of the contrast imaging protocols, also considering the emerging agents and multimodal probes.
Topics: Brain; Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasms; Positron Emission Tomography Computed Tomography
PubMed: 35937076
DOI: 10.2147/IJN.S362192 -
Drugs May 2019Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies. (Meta-Analysis)
Meta-Analysis
AIM
Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies.
METHODS
A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to January 20, 2019, in order to identify clinical trials assessing the effect of mipomersen on lipoproteins, and the safety profile of mipomersen. Effect sizes for lipid changes were expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). For safety analysis, odd ratios (OR) and 95% CI were calculated using the Mantel-Haenszel method. Data were pooled from 13 clinical studies comprising 49 arms, which included 1053 subjects overall, with 729 in the active-treated arm and 324 in the control arm.
RESULTS
Meta-analysis of data suggested that mipomersen significantly reduced low-density lipoprotein cholesterol (WMD - 1.52, 95% CI - 1.85 to - 1.19; p < 0.001), total cholesterol (WMD - 1.55, 95% CI - 1.97 to - 1.13; p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (WMD - 1.66, 95% CI - 2.06 to - 1.27; p < 0.001), lipoprotein(a) (WMD - 0.99, 95% CI - 1.37 to - 0.62; p < 0.001), apolipoprotein B (WMD - 1.66, 95% CI - 2.04 to - 1.27; p < 0.001), triglycerides (WMD -0.61, 95% CI - 0.76 to - 0.46, p < 0.001), very-low-density lipoprotein cholesterol (WMD - 0.58, 95% CI - 0.73 to - 0.43; p < 0.001) and apolipoprotein A-I (WMD - 0.25, 95% CI - 0.51 to - 0.001; p = 0.049) without affecting HDL-C levels (WMD 0.11, 95% CI - 0.03 to 0.26; p = 0.124). However, treatment with mipomersen was positively associated with an increased risk of discontinuation of treatment (OR 3.02, 95% CI 1.96-4.65; p < 0.001), injection-site reaction (OR 11.41, 95% CI 7.88-16.52; p < 0.001), hepatic steatosis (OR 4.96, 95% CI 1.99-12.39; p = 0.001), hepatic enzymes elevation (OR 3.61, 95% CI 2.09-6.24; p < 0.001) and flu-like symptoms (OR 2.02, 95% CI 1.45-2.81; p < 0.001).
CONCLUSION
Despite favourable effects on the lipid profile, some concerns are reinforced from the safety profile. As a matter of fact, mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions, hepatic steatosis, hepatic enzyme elevation, and flu-like symptoms.
Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Apolipoprotein A-I; Cholesterol, LDL; Fatty Liver; Female; Humans; Lipids; Lipoprotein(a); Male; Middle Aged; Oligonucleotides; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 30989634
DOI: 10.1007/s40265-019-01114-z -
Journal of Pediatric Genetics Sep 2020Oculoauriculovertebral spectrum (OAVS) is a rare class of heterogenous congenital craniofacial malformation conditions of unknown etiology. Although classic OAVS has... (Review)
Review
Microarray-Based Comparative Genomic Hybridization, Multiplex Ligation-Dependent Probe Amplification, and High-Resolution Karyotype for Differential Diagnosis Oculoauriculovertebral Spectrum: A Systematic Review.
Oculoauriculovertebral spectrum (OAVS) is a rare class of heterogenous congenital craniofacial malformation conditions of unknown etiology. Although classic OAVS has been described as hemifacial microsomia with facial asymmetry and microtia, there is no consensus regarding clinical criteria for diagnosis or genetic cause. This systematic review aims to assess the applicability of high-resolution (HR) karyotype, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA), and microarray-based comparative genomic hybridization (array-CGH) for differential diagnosis of OAVS. A search was performed in PubMed and Web of Science using all entry terms to the following descriptors: Goldenhar's syndrome, cytogenetic analysis, hybridization in situ, fluorescent, comparative genomic hybridization, multiplex polymerase chain reaction, whole genome sequencing, and karyotype analysis methods. After screening, 25 articles met eligibility. Of the included studies, 59 individuals had a genetic alteration identified. Array-CGH, MLPA, and HR karyotype appear to be viable approaches for molecular diagnosis in OAVS. Heterogeneity is a hallmark of OAVS. Establishing an enhanced framework for diagnosis would inform clinical decision making, and better resource utilization could improve health care facility efficiency and economy.
PubMed: 32714614
DOI: 10.1055/s-0040-1712118 -
PloS One 2015The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to... (Review)
Review
Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.
BACKGROUND
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
METHODS
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
RESULTS
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
CONCLUSIONS
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
Topics: Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Meta-Analysis as Topic; Mutation; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 25816236
DOI: 10.1371/journal.pone.0120470 -
International Journal of Molecular... Jan 2024Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like... (Meta-Analysis)
Meta-Analysis Review
Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum (HULC) gene expression with (HOTAIR) and (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Long Noncoding; Genes, Homeobox; RNA, Antisense; Carcinoma, Transitional Cell; Gene Expression Regulation, Neoplastic; Urinary Bladder Neoplasms; RNA, Untranslated; Biomarkers; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38279264
DOI: 10.3390/ijms25021258 -
Clinical Microbiology and Infection :... Dec 2021Acute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection tests (RADTs) offer diagnosis of group A streptococcus at the point of care but have limited sensitivity. Rapid nucleic acid tests (RNATs) are now available; a systematic review of their accuracy is lacking.
OBJECTIVES
To evaluate the accuracy of RNATs in patients with pharyngitis; to explore test-level and study-level factors that could explain variability in accuracy; and to compare the accuracy of RNATs with that of RADTs.
DATA SOURCES
MEDLINE, Embase, Web of Science (1990-2020).
STUDY ELIGIBILITY CRITERIA
Cross-sectional studies and randomized trials.
PARTICIPANTS
Patients with pharyngitis.
INDEX TEST/S AND REFERENCE STANDARDS
RNAT commercial kits compared with throat culture.
METHODS
We assessed risk of bias and applicability using QUADAS-2. We performed meta-analysis of sensitivity and specificity using the bivariate random-effects model. Variability was explored by subgroup analyses and meta-regression.
RESULTS
We included 38 studies (46 test evaluations; 17 411 test results). RNATs were most often performed in a laboratory. The overall methodological quality of primary studies was uncertain because of incomplete reporting. RNATs had a summary sensitivity of 97.5% (95% CI 96.2%-98.3%) and a summary specificity of 95.1% (95% CI 93.6%-96.3%). There was low variability in estimates across studies. Variability in sensitivity and specificity was partially explained by test type (p < 0.05 for both). Sensitivity analyses limited to studies with low risk of bias showed robust accuracy estimates. RNATs were more sensitive than RADTs (13 studies; 96.8% versus 82.3%, p 0.004); there was no difference in specificity (p 0.92).
CONCLUSIONS
The high diagnostic accuracy of RNATs may allow their use as stand-alone tests to diagnose group A streptococcus pharyngitis. Based on direct comparisons, RNATs have greater sensitivity than RADTs and equal specificity. Further studies should evaluate RNATs in point-of-care settings.
Topics: Humans; Nucleic Acid Amplification Techniques; Nucleic Acids; Pharyngitis; Point-of-Care Testing; Sensitivity and Specificity; Streptococcus pyogenes
PubMed: 33964409
DOI: 10.1016/j.cmi.2021.04.021 -
Frontiers in Medicine 2022Breast cancer is one of the most common malignancies in women, with high morbidity and mortality rates. In breast cancer, the use of novel radiopharmaceuticals in...
Breast cancer is one of the most common malignancies in women, with high morbidity and mortality rates. In breast cancer, the use of novel radiopharmaceuticals in nuclear medicine can improve the accuracy of diagnosis and staging, refine surveillance strategies and accuracy in choosing personalized treatment approaches, including radioligand therapy. Nuclear medicine thus shows great promise for improving the quality of life of breast cancer patients by allowing non-invasive assessment of the diverse and complex biological processes underlying the development of breast cancer and its evolution under therapy. This review aims to describe molecular probes currently in clinical use as well as those under investigation holding great promise for personalized medicine and precision oncology in breast cancer.
PubMed: 35492341
DOI: 10.3389/fmed.2022.881551 -
BMC Cancer Oct 2020DNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns...
BACKGROUND
DNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns and breast cancer risk is still lacking. The objective of this study is to provide a systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses.
METHODS
We searched major databases (MEDLINE, EMBASE, Web of Science, CENTRAL) from inception up to 30th June 2019, for observational or intervention studies investigating the association between epigenome-wide DNA methylation (using the HM450k or EPIC BeadChip), measured in any type of human sample, and breast cancer risk. A pre-established protocol was drawn up following the Cochrane Reviews rigorous methodology. Study selection, data abstraction, and risk of bias assessment were performed by at least two investigators. A qualitative synthesis and systematic comparison of the strengths and weaknesses of studies was performed.
RESULTS
Overall, 20 studies using the HM450k BeadChip were included, 17 of which had measured blood-derived DNA methylation. There was a consistent trend toward an association of global blood-derived DNA hypomethylation and higher epigenetic age with higher risk of breast cancer. The strength of associations was modest for global hypomethylation and relatively weak for most of epigenetic age algorithms. Differences in length of follow-up periods may have influenced the ability to detect associations, as studies reporting follow-up periods shorter than 10 years were more likely to observe an association with global DNA methylation. Probe-wise differential methylation analyses identified between one and 806 differentially methylated CpGs positions in 10 studies. None of the identified differentially methylated sites overlapped between studies. Three studies used breast tissue DNA and suffered major methodological issues that precludes any conclusion. Overall risk of bias was critical mainly because of incomplete control of confounding. Important issues relative to data preprocessing could have limited the consistency of results.
CONCLUSIONS
Global DNA methylation may be a short-term predictor of breast cancer risk. Further studies with rigorous methodology are needed to determine spatial distribution of DNA hypomethylation and identify differentially methylated sites associated with risk of breast cancer.
PROSPERO REGISTRATION NUMBER
CRD42020147244.
Topics: Biomarkers, Tumor; Breast Neoplasms; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Genome-Wide Association Study; Humans; Prognosis
PubMed: 33129307
DOI: 10.1186/s12885-020-07543-4 -
Journal of Lasers in Medical Sciences 2023Diabetes poses a global health challenge, giving rise to various complications, including diabetic foot ulcers (DFUs). DFUs, marked by ischemic ulcers susceptible to... (Review)
Review
Diabetes poses a global health challenge, giving rise to various complications, including diabetic foot ulcers (DFUs). DFUs, marked by ischemic ulcers susceptible to infection and amputation, underscore the urgency for innovative treatments. This study investigated the impact of photobiomodulation therapy (PBT) and autologous platelet gel (APG) on DFUs recovery. We systematically searched Web of Science, EMBASE, MEDLINE, Cochrane Library, Scopus, and Google Scholar (2015-2023) by using pertinent terms like "photobiomodulation therapy," "low level light therapy," and "platelet gel." After meticulous data extraction and review, 57 articles were chosen and categorized. Among these, three randomized controlled trials involving 186 participants were selected for APG analysis. Findings demonstrate that APG application carries minimal risk and offers promising improvements in healing time, grade, pain reduction, and granulation tissue formation. Similarly, diverse PBT modalities involving distinct probes and wavelengths exhibit the potential to enhance tissue perfusion, expedite healing, and impede wound progression, reducing the need for invasive interventions. PBT and APG emerge as valuable tools to augment wound healing, mitigate inflammation, and avert amputation, representing compelling therapeutic options for DFUs.
PubMed: 38028869
DOI: 10.34172/jlms.2023.49 -
Journal of Voice : Official Journal of... Mar 2017The reported range of involvement of human papillomavirus (HPV) in laryngeal squamous cell carcinoma (SCC) is wide because of the methods used to detect HPV. (Review)
Review
OBJECTIVE
The reported range of involvement of human papillomavirus (HPV) in laryngeal squamous cell carcinoma (SCC) is wide because of the methods used to detect HPV.
DATA SOURCES
A computerized Medline study was carried out using the following as key words: "Papillomavirus Infections"[Mesh] and "Laryngeal Neoplasms"[Mesh].
MATERIALS AND METHODS
Studies that were included were written in English and reported results of HPV DNA with RNA in laryngeal SCC.
RESULTS
There were six reported HPV mRNA extraction. Among these studies, Lewis et al reported that out of the 31 cases analyzed, only 2 were HPV DNA+ and of these only 1 was mRNA HPV+ (3%). Halec et al reported 102 cases of which 32 were HPV DNA+ cases and of which only 6 were mRNA+ (5%). Chernock et al reported 76 cases of which 13 were HPV DNA+ cases and of which 4 were mRNA+ (5%). Masand et al reported 8 cases of which 1 was HPV DNA+ case and none was mRNA+. Gheit et al reported 43 cases of which 4 were HPV DNA+ cases and of which 2 were mRNA+ (4%). Castellsagné et al reported 1042 cases of which 59 were HPV DNA+ case and of which 51 were mRNA+ (4.8%) CONCLUSIONS: When determining the role of HPV in laryngeal SCC, evidence of HPV DNA warrants further examination for E6/E7 mRNA as simple assays such as p16 are nonspecific in laryngeal SCC. Further studies of HPV and its role in laryngeal SCC are warranted.
Topics: Blotting, Southern; Carcinoma, Squamous Cell; Cell Transformation, Viral; DNA Probes, HPV; DNA, Viral; Head and Neck Neoplasms; Human Papillomavirus DNA Tests; Humans; In Situ Hybridization; Laryngeal Neoplasms; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Polymerase Chain Reaction; Predictive Value of Tests; RNA, Messenger; RNA, Viral; Reproducibility of Results; Squamous Cell Carcinoma of Head and Neck
PubMed: 27613249
DOI: 10.1016/j.jvoice.2016.08.002