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International Journal of Molecular... Dec 2022Genetic Creutzfeldt-Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrP). gCJD has... (Review)
Review
Genetic Creutzfeldt-Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrP). gCJD has a phenotypic similarity with sporadic CJD (sCJD). In Japan, gCJD with a Val to Ile substitution at codon 180 (V180I-gCJD) is the most frequent gPrD, while the mutation is extremely rare in countries other than Japan and Korea. In this article, we aim to review previously elucidated clinical and biochemical features of V180I-gCJD, expecting to advance the understanding of this unique subtype in gCJD. Compared to classical sCJD, specific clinical features of V180I-gCJD include older age at onset, a relatively slow progression of dementia, and a lower positivity for developing myoclonus, cerebellar, pyramidal signs, and visual disturbance. Diffuse edematous ribboning hyperintensity of the cerebral cortex, without occipital lobes in diffusion-weighted magnetic resonance imaging, is also specific. Laboratory data reveal the low positivity of PrP in the cerebrospinal fluid and periodic sharp wave complexes on an electroencephalogram. Most patients with V180I-gCJD have been reported to have no family history, probably due to the older age at onset, and clinical and biochemical features indicate the specific phenotype associated with the prion protein gene mutation.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prion Proteins; Prions; Codon; Mutation
PubMed: 36499498
DOI: 10.3390/ijms232315172 -
Danish Medical Journal May 2015MicroRNAs (miRNAs) are short non-coding RNAs that have the ability to regulate gene expression at the post-transcriptional level. MiRNAs are deregulated in many cancer... (Review)
Review
INTRODUCTION
MicroRNAs (miRNAs) are short non-coding RNAs that have the ability to regulate gene expression at the post-transcriptional level. MiRNAs are deregulated in many cancer types, and several miRNAs have been suggested as novel diagnostic and prognostic biomarkers in diffuse large B-cell lymphoma (DLBCL). The objective of this study was to systematically collect and evaluate current knowledge of miRNAs functioning as diagnostic and prognostic biomarkers within DLBCL.
METHODS
This review was conducted according to the Preferred Reporting for Systematic Reviews and Meta-analyses guidelines. A systematic search of literature in PubMed and Embase was made and supplemented by screening of reference lists. Only original peer-reviewed studies written in English were included and screened based on miRNA expression, molecular subtypes of DLBCL and patient outcome.
RESULTS
Out of 277 candidate records, a total of 20 studies qualified for inclusion in this review. In all, 11 studies reported a total of 48 miRNAs with expression patterns associated with specific molecular DLBCL subtypes, and 14 studies reported a total of 30 miRNAs associated with patient outcome. However, only few miRNAs showed significant results in more than one study.
CONCLUSION
MiRNAs qualify as potential diagnostic and prognostic biomarkers in DLBCL. However, more clinical validation including prospective and cross-centre studies are required before specific miRNAs can be integrated into the daily practice as biomarkers in DLBCL, which would contribute to an era of more personalised medicine.
Topics: Biomarkers; Biomarkers, Tumor; Gene Expression Profiling; Humans; Lymphoma, Large B-Cell, Diffuse; MicroRNAs; Prognosis
PubMed: 26050834
DOI: No ID Found -
Scandinavian Journal of Gastroenterology Jun 2023Diffuse peripheral neuropathy is a well-known complication of several conditions, whereas many patients have peripheral neuropathy of unknown etiology and...
INTRODUCTION
Diffuse peripheral neuropathy is a well-known complication of several conditions, whereas many patients have peripheral neuropathy of unknown etiology and pathophyisology. Increased knowledge of mechanisms may provide insight into enteric neuropathy with gastrointestinal dysmotility. The aim of the present systematic review was to identify mechanisms behind diffuse idiopathic peripheral neuropathies in humans.
METHODS
Searches were performed in PubMed, Embase, and Web of Science. Human original and review articles, written in English, describing mechanisms behind diffuse peripheral neuropathy verified by objective examinations were intended to be studied. Articles that described animal models, well-described hereditary diseases, drug-induced neuropathy, pain syndromes, malnutrition, and local neuropathy were excluded.
RESULTS
In total, 4712 articles were identified. After scrutinizing titles and abstracts, 633 remained and were studied in full text. After the removal of articles not fulfilling inclusion or exclusion criteria, 52 were finally included in this review. The most frequently described neuropathy was diabetic neuropathy, with a wide range of mechanisms involving mitochondrial dysfunction such as oxidative stress and inflammation. Microvascular changes in diabetes and vasculitis lead to ischemia and secondary oxidative stress with inflammation. Structural changes in neurons and glial cells are observed, with abnormalities in different neurotrophic factors. Neuropathy induced by autoantibodies or immunological mechanisms is described in infectious and systemic inflammatory diseases. Several ion channels may be involved in painful neuropathy. No study identified why some patients mainly develop large fiber neuropathy and others small fiber neuropathy.
CONCLUSION
Metabolic and immunological factors and channelopathy may be considered in diffuse idiopathic peripheral neuropathy.
Topics: Humans; Pain; Diabetic Neuropathies; Inflammation
PubMed: 36546668
DOI: 10.1080/00365521.2022.2160272 -
Journal of Magnetic Resonance Imaging :... Oct 2023Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify... (Review)
Review
Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal-appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.
Topics: Humans; Neurites; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Multiple Sclerosis; White Matter; Brain
PubMed: 37042392
DOI: 10.1002/jmri.28727 -
Cancers Jan 2023Adult-type diffuse gliomas are treated with a multimodality treatment approach that includes radiotherapy both in the primary setting, and in the case of progressive or... (Review)
Review
Adult-type diffuse gliomas are treated with a multimodality treatment approach that includes radiotherapy both in the primary setting, and in the case of progressive or recurrent disease. Radiation necrosis represents a major complication of radiotherapy. Recurrent disease and treatment-related changes are often indistinguishable using conventional imaging methods. The present systematic review aims at assessing the diagnostic role of PET imaging using different radiopharmaceuticals in differentiating radiation necrosis and disease relapse in irradiated adult-type diffuse gliomas. We conducted a comprehensive literature search using the PubMed/MEDLINE and EMBASE databases for original research studies of interest. In total, 436 articles were assessed for eligibility. Ten original papers, published between 2014 and 2022, were selected. Four articles focused on [F]FDG, seven on amino acid tracers ([F]FET = 3 and [C]MET = 4), one on [C]CHO, and one on [Ga]Ga-PSMA. Visual assessment, semi-quantitative methods, and radiomics were applied for image analysis. Furthermore, 2/10 papers were comparative studies investigating different radiopharmaceuticals. The present review, the first one on the topic in light of the new 2021 CNS WHO classification, highlighted the usefulness of PET imaging in distinguishing radiation necrosis and tumour recurrence, but revealed high heterogeneity among studies.
PubMed: 36672314
DOI: 10.3390/cancers15020364 -
Neurologia Medico-chirurgica Apr 2022Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent... (Meta-Analysis)
Meta-Analysis
Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of meta-regression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger pre- and postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.
Topics: Brain Neoplasms; Glioma; Humans; Incidence; Isocitrate Dehydrogenase; Mutation
PubMed: 35197400
DOI: 10.2176/jns-nmc.2021-0313 -
World Neurosurgery Sep 2022The objective of the study was to summarize the clinical characteristics, histo-genomic profiles, management strategies, and survival outcomes of H3K27M-altered adult...
OBJECTIVE
The objective of the study was to summarize the clinical characteristics, histo-genomic profiles, management strategies, and survival outcomes of H3K27M-altered adult diffuse midline gliomas (aDMGs).
METHODS
PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including H3K27M-altered aDMGs with sufficient clinical outcome data were included. Descriptive clinical characteristics and survival analysis were also conducted.
RESULTS
Twenty studies describing 135 patients were included. The median age at diagnosis was 42 years, and there was a slight male predominance (N = 60, 54%). In our cohort, 15 (11%) patients experienced headache, 10 had nausea and vomiting (7%), and 10 had ataxia (7%). Within this cohort, histopathologic diagnoses included glioblastoma (N = 22, 40%) and anaplastic astrocytoma (N = 21, 38%), while genetic alterations included ATRX mutation (N = 22, 16%), PTPN11 mutation (N = 9, 7%), and MGMT promoter methylation (N = 9, 7%). Among histo-genetic alterations, only ATRX mutation was associated with survival and correlated with worse prognosis (log-rank test, P = 0.04). Neither surgical resection versus biopsy nor greater extent of resection demonstrated survival benefit in our cohort. Chemotherapy was administered in 98 (73%) cases with radiotherapy administered in 71 (53%) cases. Unlike chemotherapy, radiotherapy demonstrated a significant survival benefit (log-rank test, P = 0.019). The median overall survival and progression-free survival within our patient cohort were 10 and 7 months, respectively.
CONCLUSIONS
H3K27M-altered aDMGs were associated with relatively poor survival. ATRX gene mutation was significantly associated with survival disadvantage, while radiotherapy was associated with survival benefit. Large, prospective studies are needed to establish a standard management strategy and provide reliable prognostic conclusions.
Topics: Adult; Astrocytoma; Brain Neoplasms; Female; Glioblastoma; Glioma; Histones; Humans; Male; Mutation; Survival Analysis
PubMed: 35697228
DOI: 10.1016/j.wneu.2022.06.020 -
Oncotarget Apr 2018Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, with highly variable outcomes among patients. Although classification and prognostic... (Review)
Review
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, with highly variable outcomes among patients. Although classification and prognostic tools have been developed, standard therapy still fails in 30-40% of patients. Hence, identification of novel biomarkers is needed. Recently, circulating microRNAs (miRNAs) have been suggested as non-invasive biomarkers in cancer. Our aim was to review the potential role of circulating miRNAs as biomarkers for diagnosis, classification, prognosis, and treatment response in DLBCL. We performed a search in PubMed using the terms [(('Non-coding RNA') OR ('microRNA' OR 'miRNA' OR 'miR') OR ('exosome') OR ('extracellular vesicle') OR ('secretome')) AND ('Diffuse large B cell lymphoma' OR 'DLBCL')] to identify articles that evaluated the impact of circulating miRNAs as diagnosis, subtype, treatment response or prognosis biomarkers in DLBCL in human population. Among the twelve articles that met the inclusion criteria, eleven considered circulating miRNAs as biomarkers for diagnosis, two for classification, and five for prognosis or treatment response. The limited number of studies performed and lack of consistency in results make it difficult to draw conclusions about the role of circulating miRNAs as non-invasive biomarkers in DLBCL. Although the preliminary associations observed seem promising, the only consistent result is the upregulation of mir-21 in DLBCL patients, which could be a biomarker for diagnosis. Further studies are needed.
PubMed: 29854319
DOI: 10.18632/oncotarget.25230 -
Artificial Organs Jun 2021Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage...
Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.
Topics: Extracorporeal Membrane Oxygenation; Hemorrhage; Humans; Lung Diseases; Pulmonary Alveoli
PubMed: 33190331
DOI: 10.1111/aor.13861 -
International Journal of Environmental... Jun 2022We aimed to review the data available to evaluate the long-term consequences of coronavirus disease 2019 (COVID-19) at 6 months and above. We searched relevant... (Meta-Analysis)
Meta-Analysis Review
We aimed to review the data available to evaluate the long-term consequences of coronavirus disease 2019 (COVID-19) at 6 months and above. We searched relevant observational cohort studies up to 9 February 2022 in Pubmed, Embase, and Web of Science. Random-effects inverse-variance models were used to evaluate the Pooled Prevalence (PP) and its 95% confidence interval (CI) of long-term consequences. The Newcastle−Ottawa quality assessment scale was used to assess the quality of the included cohort studies. A total of 40 studies involving 10,945 cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were included. Of the patients, 63.87% had at least one consequence at the 6 month follow-up, which decreased to 58.89% at 12 months. The most common symptoms were fatigue or muscle weakness (PP 6−12 m = 54.21%, PP ≥ 12 m = 34.22%) and mild dyspnea (Modified Medical Research Council Dyspnea Scale, mMRC = 0, PP 6−12 m = 74.60%, PP ≥ 12 m = 80.64%). Abnormal computerized tomography (CT; PP 6−12 m = 55.68%, PP ≥ 12 m = 43.76%) and lung diffuse function impairment, i.e., a carbon monoxide diffusing capacity (DLCO) of < 80% were common (PP 6−12 m = 49.10%, PP ≥ 12 m = 31.80%). Anxiety and depression (PP 6−12 m = 33.49%, PP ≥ 12 m = 35.40%) and pain or discomfort (PP 6−12 m = 33.26%, PP ≥ 12 m = 35.31%) were the most common problems that affected patients’ quality of life. Our findings suggest a significant long-term impact on health and quality of life due to COVID-19, and as waves of ASRS-CoV-2 infections emerge, the long-term effects of COVID-19 will not only increase the difficulty of care for COVID-19 survivors and the setting of public health policy but also might lead to another public health crisis following the current pandemic, which would also increase the global long-term burden of disease.
Topics: COVID-19; Dyspnea; Humans; Pandemics; Quality of Life; SARS-CoV-2
PubMed: 35682448
DOI: 10.3390/ijerph19116865