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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 -
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 -
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 -
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 -
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 -
BMC Cancer May 2022Extracellular vesicle (EV) biomarkers have promising diagnosis and screening capacity for several cancers, but the diagnostic value for pancreatic cancer (PC) is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Extracellular vesicle (EV) biomarkers have promising diagnosis and screening capacity for several cancers, but the diagnostic value for pancreatic cancer (PC) is controversial. The aim of our study was to review the diagnostic performance of EV biomarkers for PC.
METHODS
We performed a systematic review of PubMed, Medline, and Web Of Science databases from inception to 18 Feb 2022. We identified studies reporting the diagnostic performance of EV biomarkers for PC and summarized the information of sensitivity, specificity, area under the curve (AUC), or receiver operator characteristic (ROC) curve) in according to a pre-designed data collection form. Pooled sensitivity and specificity was calculated using a random-effect model.
RESULTS
We identified 39 studies, including 2037 PC patients and 1632 noncancerous, seven of which were conducted independent validation tests. Seventeen studies emphasized on EV RNAs, sixteen on EV proteins, and sixteen on biomarker panels. MiR-10b, miR-21, and GPC1 were the most frequently reported RNA and protein for PC diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 79% (95% CI: 77-81%) and 87% (95% CI: 85-89%), 72% (95% CI: 69-74%) and 77% (95% CI: 74-80%), respectively. the pooled sensitivity and specificity of EV RNA combined with protein panels were 84% (95% CI: 81-86%) and 89% (95% CI: 86-91%), respectively. Surprisingly, for early stage (stage I and II) PC EV biomarkers showed excellent diagnostic performance with the sensitivity of 90% (95% CI: 87-93%) and the specificity of 94% (95% CI: 92-95%). Both in sensitivity and subgroup analyses, we did not observe notable difference in pooled sensitivity and specificity. Studies might be limited by the isolation and detection techniques of EVs to a certain extent.
CONCLUSIONS
EV biomarkers showed appealing diagnostic preference for PC, especially for early stage PC. Solving the deficiency of technologies of isolation and detection EVs has important implications for application these novel noninvasive biomarkers in clinical practice.
Topics: Biomarkers; Biomarkers, Tumor; Extracellular Vesicles; Humans; MicroRNAs; Pancreatic Neoplasms
PubMed: 35606727
DOI: 10.1186/s12885-022-09463-x -
Advanced Biology Jul 2023Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals...
Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals with prostate cancer (PCa) with cancer-free samples for diagnostic purposes. The aim of this study is to review miRNA signatures to investigate the overlap between miRNAs enriched in PCa tissue and miRNAs enriched in EVs isolated from subjects with PCa biofluids (i.e., urine, serum, and plasma). Signatures dysregulated in EVs from PCa biofluids and tissue are potentially associated with the primary tumor site and might be more indicative of PCa at an early stage. A systematic review of EV-derived miRNAs and a reanalysis of PCa tissue miRNA sequencing data for comparison is presented. Articles in the literature are screened for validated miRNA dysregulation in PCa and compared with TCGA primary PCa tumor data using DESeq2. This resulted in 190 dysregulated miRNAs being identified. Thirty-one eligible studies are identified, indicating 39 dysregulated EV-derived miRNAs. The top ten markers identified as significantly dysregulated in the PCa tissue dataset TCGA (e.g., miR-30b-3p, miR-210-3p, miR-126-3p, and miR-196a-5p) have a significant expression change in EVs with the same directionality in one or several statistically significant results. This analysis highlights several less frequently studied miRNAs in PCa literature.
Topics: Male; Humans; MicroRNAs; Prostatic Neoplasms; Extracellular Vesicles
PubMed: 37300338
DOI: 10.1002/adbi.202200327 -
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 -
Scandinavian Journal of Urology Aug 2017The aim of this study was to review the management of patients with symptomatic seminal vesicle calculi, from presentation and diagnosis to postoperative outcomes. (Review)
Review
OBJECTIVE
The aim of this study was to review the management of patients with symptomatic seminal vesicle calculi, from presentation and diagnosis to postoperative outcomes.
MATERIALS AND METHODS
A systematic review of the English literature in MEDLINE and Embase was performed, based on the following model: patients with a diagnosis of seminal vesicle calculi; all interventions considered with or without control groups with single and comparator interventions; outcomes considered were incidence, presentation, diagnostic methods and treatment. A narrative synthesis of the data was performed according to PRISMA 2009 guidelines. The study protocol was registered on PROSPERO (CRD42016032971).
RESULTS
In total, 213 cases of seminal vesicle calculi from 37 studies were identified between 1928 and 2016. Published articles included cohort studies (16), case-control studies (two) and case reports (19). The most likely aetiology was stasis of ejaculate secondary to impaired drainage of secretions from the seminal vesicles. Transrectal ultrasound remains the primary investigation for haematospermia and painful ejaculation; however, magnetic resonance imaging seems to play an increasingly important role, especially when considering surgery. Transurethral seminal vesiculoscopy and lithotripsy is the ideal procedure for small calculi but requires surgical expertise. For larger calculi a transperitoneal laparoscopic approach is safe in the hands of experienced laparoscopic surgeons.
CONCLUSIONS
Modern imaging techniques and cross-sectional imaging are leading to an increased number of diagnosed cases of seminal vesicle calculi. Optimal treatment depends on the stone size and burden, and centralization of services will assist in the development of specialized centres.
Topics: Calculi; Endoscopy; Endosonography; Genital Diseases, Male; Humans; Lithotripsy; Magnetic Resonance Imaging; Male; Seminal Vesicles
PubMed: 28332431
DOI: 10.1080/21681805.2017.1295398