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Journal of Extracellular Biology Nov 2023Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive... (Review)
Review
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are often misdiagnosed due to overlapping symptoms and the absence of precise biomarkers. Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta-analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta-analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta-analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim-and-fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF-EVs showed better overall diagnostic accuracy, while plasma-EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS-originating EVs, which are more time-consuming, labour- and cost-intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV) aim to enhance the accuracy and reproducibility of EV-related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.
PubMed: 38939363
DOI: 10.1002/jex2.121 -
AJNR. American Journal of Neuroradiology Jun 2024Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma...
BACKGROUND
Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma reporting, have been applied for a decade, but a systematic performance evaluation is lacking.
PURPOSE
Our aim was to conduct a systematic review and meta-analysis of the performance of the VASARI features set for glioma assessment.
DATA SOURCES
MEDLINE, Web of Science, EMBASE, and the Cochrane Library were systematically searched until September 26, 2023.
STUDY SELECTION
Original articles predicting diagnosis, progression, and survival in patients with glioma were included.
DATA ANALYSIS
The modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to evaluate the risk-of-bias. The meta-analysis used a random effects model and forest plot visualizations, if ≥5 comparable studies with a low or medium risk of bias were provided.
DATA SYNTHESIS
Thirty-five studies (3304 patients) were included. Risk-of-bias scores were medium ( = 33) and low ( = 2). Recurring objectives were overall survival ( = 18) and isocitrate dehydrogenase mutation (; = 12) prediction. Progression-free survival was examined in 7 studies. In 4 studies (glioblastoma = 2, grade 2/3 glioma = 1, grade 3 glioma = 1), a significant association was found between progression-free survival and single VASARI features. The single features predicting overall survival with the highest pooled hazard ratios were multifocality (hazard ratio = 1.80; 95%-CI, 1.21-2.67; I = 53%), ependymal invasion (hazard ratio = 1.73; 95% CI, 1.45-2.05; I = 0%), and enhancing tumor crossing the midline (hazard ratio = 2.08; 95% CI, 1.35-3.18; I = 52%). mutation-predicting models combining VASARI features rendered a pooled area under the receiver operating characteristic curve of 0.82 (95% CI, 0.76-0.88) at considerable heterogeneity (I = 100%). Combined input models using VASARI plus clinical and/or radiomics features outperformed single data-type models in all relevant studies ( = 17).
LIMITATIONS
Studies were heterogeneously designed and often with a small sample size. Several studies used The Cancer Imaging Archive database, with likely overlapping cohorts. The meta-analysis for was limited due to a high study heterogeneity.
CONCLUSIONS
Some VASARI features perform well in predicting overall survival and mutation status, but combined models outperform single features. More studies with less heterogeneity are needed to increase the evidence level.
PubMed: 38937115
DOI: 10.3174/ajnr.A8274 -
International Journal of Molecular... Jun 2024The process of identification and management of neurological disorder conditions faces challenges, prompting the investigation of novel methods in order to improve... (Review)
Review
The process of identification and management of neurological disorder conditions faces challenges, prompting the investigation of novel methods in order to improve diagnostic accuracy. In this study, we conducted a systematic literature review to identify the significance of genetics- and molecular-pathway-based machine learning (ML) models in treating neurological disorder conditions. According to the study's objectives, search strategies were developed to extract the research studies using digital libraries. We followed rigorous study selection criteria. A total of 24 studies met the inclusion criteria and were included in the review. We classified the studies based on neurological disorders. The included studies highlighted multiple methodologies and exceptional results in treating neurological disorders. The study findings underscore the potential of the existing models, presenting personalized interventions based on the individual's conditions. The findings offer better-performing approaches that handle genetics and molecular data to generate effective outcomes. Moreover, we discuss the future research directions and challenges, emphasizing the demand for generalizing existing models in real-world clinical settings. This study contributes to advancing knowledge in the field of diagnosis and management of neurological disorders.
Topics: Humans; Machine Learning; Nervous System Diseases
PubMed: 38928128
DOI: 10.3390/ijms25126422 -
Biomedicines May 2024Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is... (Review)
Review
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.
PubMed: 38927416
DOI: 10.3390/biomedicines12061209 -
Journal of Clinical and Experimental... 2024Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with...
Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "atypical lymphoplasmacytic and immunoblastic lymphadenopathy" from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial.
Topics: Humans; Female; Male; Middle Aged; Lymphoproliferative Disorders; Lymphadenopathy; Lymph Nodes; Autoimmune Diseases
PubMed: 38925977
DOI: 10.3960/jslrt.24007 -
Frontiers in Medicine 2024Tuberculosis is a contagious bacterial disease caused by . The emergence and spread of drug-resistant strains of in both developing and developed countries has made...
INTRODUCTION
Tuberculosis is a contagious bacterial disease caused by . The emergence and spread of drug-resistant strains of in both developing and developed countries has made diagnosis, treatment, and control of tuberculosis more difficult. The PCR assay, which is a fast and sensitive technique and an alternative method for detecting multidrug-resistant tuberculosis, is used to determine rifampicin (RIF) resistance. There is no single figure in Ethiopia that represents rifampicin-resistant tuberculosis and that is why this study was conducted to overcome the inconsistency of the results of the previous studies.
METHODS
Studies were researched from five major electronic databases. Studies which were cross-sectional in design, published, and written in English were included. The data were extracted using Microsoft Excel, and the data were managed and analyzed using Stata™ Version 17.0 statistical software. The Forest plot was used to check the presence of heterogeneity. The publication bias, meta-regression, and subgroup analysis were used to find out the source of heterogeneity. A random effect analysis model was used to pool the prevalence of RR TB from primary studies, and associated factors of RR among TB patients were identified using Meta regression. The presence of association was reported using OR with 95% CI.
RESULTS
The overall pooled prevalence of tuberculosis was 14.9% (95% CI: 13.34, 16.46), of these approximately 7.48% (95% CI: 6.30, 8.66) showed rifampicin-resistant tuberculosis in Ethiopia. Among the computed variables, 2.05% living with HIV1.39 (95%CI: 1.13, 1.72) and having a history of TB treatment (95%CI: 1.34, 3.15) were identified as significant factors associated with RR TB in Ethiopia.
CONCLUSION
Drug-resistant TB is one of the prevalent emerging infectious diseases among TB patients, which affects approximately one out of every thirteen TB patients. Having TB-HIV coinfection and a history of prior TB treatment were identified as significant factors associated with RR TB. To prevent and control RR TB, patients should complete their follow-up course; the health professionals should educate the actions taken by the patients when they experience drug toxicity and side effects; and the Minister of Health should initiate telemedicine and recruit tracers to overcome TB patients' default and have good drug adherence and retention after initiation of the treatment.
PubMed: 38912342
DOI: 10.3389/fmed.2024.1319845 -
European Radiology Jun 2024Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
BACKGROUND
Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
PURPOSE
This article is dedicated to comparing the diagnostic efficacy of FAPI PET and [F]fluorodeoxyglucose (FDG) PET in the evaluation of primary tumors, lymph nodes, and distant metastases in pancreatic cancer.
METHODS
In this review, we conducted a systematic search of studies published in PubMed and Web of Science databases up to September 18, 2023. All included studies used radionuclide labeled FAPI and FDG as PET diagnostic tracers to evaluate their applicability in patients with pancreatic cancer.
RESULTS
The FAPI PET imaging group showed significantly higher sensitivity in the detection of primary lesions (1.000, [95% CI: 0.999-1.000]), lymph node metastases (0.624 [95% CI: 0.391-0.834]) and distant metastatic (0.965 [95% CI: 0.804-1.000]) in pancreatic cancer compared to the FDG PET imaging group (0.889 [95% CI: 0.788-0.966], 0.373 [95% CI: 0.163-0.606] and 0.889 [95% CI: 0.689-0.999], respectively). Furthermore, the maximum standardized uptake value (SUVmax) in FAPI PET imaging is significantly higher than that in FDG imaging for primary lesions (mean difference (MD) = 7.51, 95% CI: 5.34-9.67).
CONCLUSION
Compared with [F]FDG PET/CT, FAPI PET imaging showed higher sensitivity, SUVmax. This method can be effectively utilized for the evaluation of pancreatic cancer.
CLINICAL RELEVANCE STATEMENT
Fibroblast activating protein inhibitor PET may be a better alternative to [F]FDG in evaluating primary pancreatic cancer, lymph node metastases, and distant metastases.
KEY POINTS
Fibroblast activating protein inhibitor (FAPI) PET is compared with FDG PET for evaluating pancreatic cancer. Multiple radiolabeled FAPI variants have shown promising results in the diagnosis of pancreatic cancer. FAPI PET imaging effectively helps clinicians diagnose and stage pancreatic cancer.
PubMed: 38907099
DOI: 10.1007/s00330-024-10843-z -
European Urology Focus Jun 2024Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited... (Review)
Review
BACKGROUND AND OBJECTIVE
Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one.
METHODS
The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703.
KEY FINDINGS AND LIMITATIONS
Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR.
CONCLUSIONS AND CLINICAL IMPLICATIONS
DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies.
PATIENT SUMMARY
In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.
PubMed: 38897871
DOI: 10.1016/j.euf.2024.05.024 -
Seizure Jun 2024To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs).
OBJECTIVE
To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs).
METHODS
This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed.
RESULTS
The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old.
CONCLUSION
Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.
PubMed: 38897163
DOI: 10.1016/j.seizure.2024.06.013 -
Frontiers in Oncology 2024Breast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is...
BACKGROUND
Breast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is a medical intervention that focuses on specific molecular markers. This study aims to investigate and evaluate the current research trends and directions in the field of targeted therapy for breast cancer using bibliometric analysis.
METHOD
The Web of Science database was utilized to retrieve relevant articles published between 2003 and 2022. The VOSviewer software and Bibliometrix package in the R language were employed to conduct co-occurrence and clustering analyses of authors, countries, institutions, journals, references, and the CiteSpace tool was utilized for keyword burst detection.
RESULTS
A total of 2,258 articles were included and the annual number of publications increased rapidly. The most prolific country on this topic was the USA (n=898, 39.77%) and the University of Texas MD Anderson Cancer Center published most papers (n=93). Dennis J. Slamon and Gabriel N. Hortobagyi stood out in the field, with Dennis J. Slamon leading in terms of co-citations(n=653) and Gabriel N. Hortobagyi topping the list in terms of published articles(n=18). The most productive journal was Breast Cancer Research and Treatment and the most cited journal was Journal of Clinical Oncology. The clustering of keywords indicated that the primary focus of researches in the past two decades was on the development and clinical evaluation of tumor-targeted drugs associated with the epidermal growth factor receptor (EGFR) family signaling pathway, and explored mechanisms related to biological behavior of breast cancer. Keywords co-occurrence and burst analysis identified current research hotspots and potential research trends.
CONCLUSION
This study employed bibliometric analysis to examine research on targeted therapy for breast cancer over a span of 20 years, and identified development trends of research and elucidated potential research trajectories in the domain of this topic. This study helps in the identification of prospective collaborators and partner institutions for researchers.
PubMed: 38894873
DOI: 10.3389/fonc.2024.1366900