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European Urology Jul 2023Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of... (Meta-Analysis)
Meta-Analysis Review
Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of intermediate-high risk prostate cancer (PCa) requires definitive evidence on their relative diagnostic abilities.
OBJECTIVE
To perform head-to-head comparisons of PSMA-PET and CIM including multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) for upfront staging of tumour, nodal, and bone metastasis.
EVIDENCE ACQUISITION
A search of the PubMed, EMBASE, CENTRAL, and Scopus databases was conducted from inception to December 2021. Only studies in which patients underwent both PSMA-PET and CIM and imaging was referenced against histopathology or composite reference standards were included. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist and its extension for comparative reviews (QUADAS-C). Pairwise comparisons of the sensitivity and specificity of PSMA-PET versus CIM were performed by adding imaging modality as a covariate to bivariate mixed-effects meta-regression models. The likelihood ratio test was applied to determine whether statistically significant differences existed.
EVIDENCE SYNTHESIS
A total of 31 studies (2431 patients) were included. PSMA-PET/MRI was more sensitive than mpMRI for detection of extra-prostatic extension (78.7% versus 52.9%) and seminal vesicle invasion (66.7% versus 51.0%). For nodal staging, PSMA-PET was more sensitive and specific than mpMRI (73.7% versus 38.9%, 97.5% versus 82.6%) and CT (73.2% versus 38.5%, 97.8% versus 83.6%). For bone metastasis staging, PSMA-PET was more sensitive and specific than BS with or without single-photon emission computerised tomography (98.0% versus 73.0%, 96.2% versus 79.1%). A time interval between imaging modalities >1 month was identified as a source of heterogeneity across all nodal staging analyses.
CONCLUSIONS
Direct comparisons revealed that PSMA-PET significantly outperforms CIM, which suggests that PSMA-PET should be used as a first-line approach for the initial staging of PCa.
PATIENT SUMMARY
We reviewed direct comparisons of the ability of a scan method called PSMA-PET (prostate-specific membrane antigen positron emission tomography) and current imaging methods to detect the spread of prostate cancer outside the prostate gland. We found that PSMA-PET is more accurate for detection of the spread of prostate cancer to adjacent tissue, nearby lymph nodes, and bones.
Topics: Male; Humans; Prostate; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Magnetic Resonance Imaging; Gallium Radioisotopes; Neoplasm Staging
PubMed: 37032189
DOI: 10.1016/j.eururo.2023.03.001 -
Neural Regeneration Research Nov 2022Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring... (Review)
Review
Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).
PubMed: 35535875
DOI: 10.4103/1673-5374.335832 -
Theranostics 2022Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We... (Meta-Analysis)
Meta-Analysis Review
Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We conducted a systematic review of the available evidence to assess sEV therapeutic efficacy and safety in wound healing and skin regeneration in animal models. 68 studies were identified in Web of Science, Scopus, and PubMed that satisfied a set of prespecified inclusion criteria. We critically analyzed the quality of studies that satisfied our inclusion criteria, with an emphasis on methodology, reporting, and adherence to relevant guidelines (including MISEV2018 and ISCT criteria). Overall, our systematic review and meta-analysis indicated that sEV interventions promoted skin regeneration in diabetic and non-diabetic animal models and influenced various facets of the healing process regardless of cell source, production protocol and disease model. The EV source, isolation methods, dosing regimen, and wound size varied among the studies. Modification of sEVs was achieved mainly by manipulating source cells via preconditioning, nanoparticle loading, genetic manipulation, and biomaterial incorporation to enhance sEV therapeutic potential. Evaluation of potential adverse effects received only minimal attention, although none of the studies reported harmful events. Risk of bias as assessed by the SYRCLE's ROB tool was uncertain for most studies due to insufficient reporting, and adherence to guidelines was limited. In summary, sEV therapy has enormous potential for wound healing and skin regeneration. However, reproducibility and comprehensive evaluation of evidence are challenged by a general lack of transparency in reporting and adherence to guidelines. Methodological rigor, standardization, and risk analysis at all stages of research are needed to promote translation to clinical practice.
Topics: Animals; Biocompatible Materials; Extracellular Vesicles; Reproducibility of Results; Skin; Wound Healing
PubMed: 36185607
DOI: 10.7150/thno.73436 -
Journal of Cosmetic Dermatology Sep 2023Exosomes are small extracellular vesicles with potential roles in modulating the hair growth cycle and are an emerging therapy for patients with alopecia. In recent... (Review)
Review
BACKGROUND
Exosomes are small extracellular vesicles with potential roles in modulating the hair growth cycle and are an emerging therapy for patients with alopecia. In recent years, researchers have made significant progress in deciphering the network of cellular interactions and signaling pathways mediated by the transfer of exosomes. This has opened the door to a wide range of potential therapeutic applications with an increasing focus on its application in precision medicine.
AIM
To evaluate current published evidence, both preclinical and clinical, on the use of exosomes for hair restoration.
METHODS
In January 2023, a systematic search was conducted using PubMed, Embase, and the Cochrane Library. Records were identified, screened, and assessed for eligibility as per the PRISMA guideline.
RESULTS
We identified 16 studies (15 preclinical and 1 clinical) showing varying degrees of efficacy using exosomes derived from sources including adipose-derived stem cells (ADSCs) and dermal papilla cells (DPCs). Applications of exosomes isolated from ADSCs (ADSC-Exo) and DPCs have shown early promising results in preclinical studies corroborated by results obtained from different model systems. Topical ADSC-Exo has been tried successfully in 39 androgenetic alopecia patients demonstrating significant increases in hair density and thickness. No significant adverse reactions associated with exosome treatment have been reported thus far.
CONCLUSIONS
Although current clinical evidence supporting the use of exosome treatment is limited, there is a growing body of evidence suggesting its therapeutic potential. Further studies are warranted to define its mechanism of action, optimize its delivery and efficacy, and to address important safety concerns.
Topics: Humans; Exosomes; Adipose Tissue; Hair; Adipocytes; Alopecia
PubMed: 37381168
DOI: 10.1111/jocd.15869 -
International Journal of Environmental... Dec 2022Peristomal skin complications (PSCs) are the most common skin problems seen after ostomy surgery. They have a considerable impact on a patient's quality of life and... (Review)
Review
BACKGROUND
Peristomal skin complications (PSCs) are the most common skin problems seen after ostomy surgery. They have a considerable impact on a patient's quality of life and contribute to a higher cost of care.
METHODS
A systematic review was conducted, querying three databases. The analysis was performed on international studies focused on the clinical-epidemiological burden of PSCs in adult patients with ileostomy/colostomy.
RESULTS
Overall, 23 studies were considered. The main diseases associated with ostomy surgery were rectal, colon and gynecological cancers, inflammatory bowel diseases, diverticulitis, bowel obstruction and intestinal perforation. Erythema, papules, skin erosions, ulcers and vesicles were the most common PSCs for patients with an ostomy (or stoma). A PSCs incidence ranging from 36.3% to 73.4% was described. Skin complications increased length of stay (LOS) and rates of readmission within 120 days of surgery.
CONCLUSIONS
PSCs data are still limited. A knowledge of their burden is essential to support health personnel and decision-makers in identifying the most appropriate responses to patients' needs. Proper management of these complications plays a fundamental role in improving the patient's quality of life. A multidisciplinary approach, as well as increased patient education and their empowerment, are priority measures to be implemented to foster a value-based healthcare.
Topics: Adult; Humans; Colostomy; Ileostomy; Quality of Life; Public Health; Erythema
PubMed: 36612395
DOI: 10.3390/ijerph20010079 -
Urologic Oncology Nov 2023Extracellular vesicle (EV) biomarkers have promising diagnostic and screening capabilities for several cancers, and growing evidence indicates that EV biomarkers can be... (Meta-Analysis)
Meta-Analysis Review
Extracellular vesicle (EV) biomarkers have promising diagnostic and screening capabilities for several cancers, and growing evidence indicates that EV biomarkers can be used as diagnostic markers for prostate cancer (CaP). However, data on the diagnostic accuracy of EV biomarkers for CaP diagnosis are conflicting. We performed a systematic review and meta-analysis, aimed to summarize the diagnostic performance of EV biomarkers for CaP. We systematically searched PubMed, Medline, and Web of Science from inception to 12 September 2022 for studies that assessed the diagnostic accuracy of EV biomarkers for CaP. We summarized the pooled sensitivity and specificity calculated using a random-effects model. We identified 19 studies involving 976 CaP patients and 676 noncancerous controls; one study conducted independent validation tests. Ten studies emphasized EV RNAs, 6 on EV proteins, and 9 on biomarker panels. MiR-141, miR-221, and PSMA were the most frequently reported RNAs and proteins for CaP diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 70% (95% CI: 68%-71%), 79% (95% CI: 77%-80%), 85% (95% CI: 81%-87%), and 83% (95% CI: 80%-86%), respectively. The pooled sensitivity and specificity of the EV panels were 84% (95% CI: 82%-86%) and 86% (95% CI: 84%-88%), respectively. The studies may have been somewhat limited by the EV isolation and detection techniques. EV biomarkers showed promising diagnostic capability for CaP. Addressing deficiencies in EV isolation and detection techniques has important implications for the application of these novel noninvasive biomarkers in clinical practice.
Topics: Male; Humans; Biomarkers; MicroRNAs; Prostatic Neoplasms; Sensitivity and Specificity; Extracellular Vesicles; Biomarkers, Tumor
PubMed: 37914569
DOI: 10.1016/j.urolonc.2023.08.019 -
Thrombosis Research Dec 2022Evidence of micro- and macro-thrombi in the arteries and veins of critically ill COVID-19 patients and in autopsies highlight the occurrence of COVID-19-associated... (Review)
Review
Evidence of micro- and macro-thrombi in the arteries and veins of critically ill COVID-19 patients and in autopsies highlight the occurrence of COVID-19-associated coagulopathy (CAC). Clinical findings of critically ill COVID-19 patients point to various mechanisms for CAC; however, the definitive underlying cause is unclear. Multiple factors may contribute to the prothrombotic state in patients with COVID-19. Aberrant expression of tissue factor (TF), an initiator of the extrinsic coagulation pathway, leads to thrombotic complications during injury, inflammation, and infections. Clinical evidence suggests that TF-dependent coagulation activation likely plays a role in CAC. Multiple factors could trigger abnormal TF expression and coagulation activation in patients with severe COVID-19 infection. Proinflammatory cytokines that are highly elevated in COVID-19 (IL-1β, IL-6 and TNF-α) are known induce TF expression on leukocytes (e.g. monocytes, macrophages) and non-immune cells (e.g. endothelium, epithelium) in other conditions. Antiphospholipid antibodies, TF-positive extracellular vesicles, pattern recognition receptor (PRR) pathways and complement activation are all candidate factors that could trigger TF-dependent procoagulant activity. In addition, coagulation factors, such as thrombin, may further potentiate the induction of TF via protease-activated receptors on cells. In this systematic review, with other viral infections, we discuss potential mechanisms and cell-type-specific expressions of TF during SARS-CoV-2 infection and its role in the development of CAC.
Topics: Humans; Thromboplastin; COVID-19; Critical Illness; SARS-CoV-2; Blood Coagulation Disorders; Thrombosis
PubMed: 36265412
DOI: 10.1016/j.thromres.2022.09.025 -
Acta Biomaterialia Dec 2022Osteoarthritis (OA) is a degenerative joint disease and is the main cause of chronic pain and functional disability in adults. Articular cartilage is a hydrated soft... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease and is the main cause of chronic pain and functional disability in adults. Articular cartilage is a hydrated soft tissue that is composed of normally quiescent chondrocytes at a low density, a dense network of collagen fibrils with a pore size of 60-200 nm, and aggrecan proteoglycans with high-density negative charge. Although certain drugs, nucleic acids, and proteins have the potential to slow the progression of OA and restore the joints, these treatments have not been clinically applied owing to the lack of an effective delivery system capable of breaking through the cartilage barrier. Recently, the development of nanotechnology for delivery systems renders new ideas and treatment methods viable in overcoming the limited penetration. In this review, we focus on current research on such applications of nanotechnology, including exosomes, protein-based cationic nanocarriers, cationic liposomes/solid lipid nanoparticles, amino acid-based nanocarriers, polyamide derivatives-based nanocarriers, manganese dioxide, and carbon nanotubes. Exosomes are the smallest known nanoscale extracellular vesicles, and they can quickly deliver nucleic acids or proteins to the required depth. Through electrostatic interactions, nanocarriers with appropriate balance in cationic property and particle size have a strong ability to penetrate cartilage. Although substantial preclinical evidence has been obtained, further optimization is necessary for clinical transformation. STATEMENT OF SIGNIFICANCE: The dense cartilage matrix with high-negative charge was associated with reduced therapeutic effect in osteoarthritis patients with deep pathological changes. However, a systematic review in nanodevices for deep cartilage penetration is still lacking. Current approaches to assure penetration of nanosystems into the depth of cartilage were reviewed, including nanoscale extracellular vesicles from different cell lines and nanocarriers with appropriate balance in cationic property and size particle. Moreover, nanodevices entering clinical trials and further optimization were also discussed, providing important guiding significance to future research.
Topics: Adult; Humans; Osteoarthritis; Nanotubes, Carbon; Cartilage, Articular; Chondrocytes; Cations; Proteins; Nucleic Acids
PubMed: 36243371
DOI: 10.1016/j.actbio.2022.10.007 -
Traffic (Copenhagen, Denmark) Dec 2021Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking... (Review)
Review
Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking machinery incorporates a wide array of cargo proteins into vesicles through direct or indirect interactions with Sec24, the principal subunit of the COPII coat. Approximately one-third of all mammalian proteins rely on the COPII-mediated secretory pathway for membrane insertion or secretion. There are four mammalian Sec24 paralogs and three yeast Sec24 paralogs with emerging evidence of paralog-specific cargo interaction motifs. Furthermore, individual paralogs also differ in their affinity for a subset of sorting motifs present on cargo proteins. As with many aspects of protein trafficking, we lack a systematic and thorough understanding of the interaction of Sec24 with cargoes. This systematic review focuses on the current knowledge of cargo binding to both yeast and mammalian Sec24 paralogs and their ER export motifs. The analyses show that Sec24 paralog specificity of cargo (and cargo receptors) range from exclusive paralog dependence or preference to partial redundancy. We also discuss how the Sec24 secretion system is hijacked by viral (eg, VSV-G, Hepatitis B envelope protein) and bacterial (eg, the enteropathogenic Escherichia coli type III secretion system effector NleA/EspI) pathogens.
Topics: Animals; COP-Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Mammals; Membrane Proteins; Protein Transport; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Secretory Pathway
PubMed: 34533884
DOI: 10.1111/tra.12817 -
Cancers Sep 2021Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the... (Review)
Review
Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the fatality resultant of cancer is the development of resistance to chemotherapy, known as chemoresistance. Furthermore, there are limitations in our ability to identify patients that will respond to therapy, versus patients that will develop relapse, and display limited or no response to treatment. This often leads to patients being subjected to multiple futile treatment cycles, and results in a reduction in their quality of life. Therefore, there is an urgent clinical need to develop tools to identify patients at risk of chemoresistance, and recent literature has suggested that small extracellular vesicles, known as exosomes, may be a vital source of information. Extracellular vesicles (EV) are membrane bound vesicles, involved in cell-cell communication, through the transfer of their cargo, which includes proteins, lipids, and miRNAs. A defined exploration strategy was performed in this systematic review in order to provide a compilation of key EV miRNAs which may be predictive of chemoresistance. We searched the PubMed, Science Direct, and Scopus databases using the following keywords: Extracellular vesicles OR exosomes OR EVs AND miRNA AND Chemotherapy OR Chemoresistance OR Cancer Recurrence from 2010 to 2020. We found 31 articles that reported key EV-associated miRNAs involved in cancer recurrence related to chemoresistance. Interestingly, multiple studies of the same tumor type identified different microRNAs, and few studies identified the same ones. Specifically, miR-21, miR-222, and miR-155 displayed roles in response to chemotherapy, and were found to be common in colorectal cancer, ovarian cancer, breast cancer, and diffuse large B cell lymphoma patients (DLBCL). miR-21 and miR-222 were found to favour the development of chemoresistance, whereas miR-155 exhibited a contrasting role, depending on the type of primary tumor. Whilst high levels of miR-155 were found to correlate with chemotherapy resistance in DLBCL, it was found to be predictive of an effective response towards chemotherapy in breast cancer. Thus, further research regarding the roles of these miRNAs would be beneficial in terms of designing novel tools to counteract the progression of cancer in a not-to-distant future.
PubMed: 34572835
DOI: 10.3390/cancers13184608