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World Journal of Gastroenterology Aug 2023Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of NAFLD is widely recognised, the precise triggers for disease progression are still to be fully elucidated. Furthermore, the propagation to cirrhosis is poorly understood. Whilst some progress in terms of treatment options have been explored, an incomplete understanding of the hepatic cellular and molecular alterations limits their clinical utility. We have therefore reviewed some of the key pathways responsible for the pathogenesis of NAFLD such as innate and adaptative immunity, lipotoxicity and fibrogenesis, and highlighted current trials and treatment options for NAFLD patients.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Adaptive Immunity; Disease Progression; Global Burden of Disease; Hepatocytes
PubMed: 37701135
DOI: 10.3748/wjg.v29.i32.4831 -
Frontiers in Immunology 2023Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease... (Review)
Review
UNLABELLED
Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Topics: Humans; Aged; Alzheimer Disease; Biomarkers; Disease Progression; Multiple Sclerosis
PubMed: 37520580
DOI: 10.3389/fimmu.2023.1162340 -
Annals of Clinical and Translational... Oct 2023Our aim was to study the evolution of ataxia and neurological symptoms before and after ataxia onset in the most common spinocerebellar ataxias (SCAs), SCA1, SCA2, SCA3...
OBJECTIVE
Our aim was to study the evolution of ataxia and neurological symptoms before and after ataxia onset in the most common spinocerebellar ataxias (SCAs), SCA1, SCA2, SCA3 and SCA6. We therefore jointly analysed the data of the EUROSCA and RISCA studies, which recruited ataxic and non-ataxic mutation carriers.
METHODS
We used mixed effect models to analyse the evolution of Scale for the Rating and Assessment of Ataxia (SARA) scores, SCA Functional Index (SCAFI) and Inventory of Non-Ataxia Signs (INAS) counts. We applied multivariable modelling to identify factors associated with SARA progression. In the time interval 5 years prior to and after ataxia onset, we calculated sensitivity to change ratios (SCS) of SARA, SCAFI and INAS.
RESULTS
2740 visits of 677 participants were analysed. All measures showed non-linear progression that was best fitted by linear mixed models with linear, quadratic and cubic time effects. R values indicating quality of the fit ranged from 0.70 to 0.97. CAG repeat was associated with faster progression in SCA1, SCA2 and SCA3, but not SCA6. 5 years prior to and after ataxia onset, SARA had the highest SCS of all measures with a mean of 1.21 (95% CI: 1.20, 1.21) in SCA1, 0.94 (0.93, 0.94) in SCA2 and 1.23 (1.22, 1.23) in SCA3.
INTERPRETATION
Our data have important implications for the understanding of disease progression in SCA1, SCA2, SCA3 and SCA6 across the lifespan. Furthermore, our study provides information for the design of interventional trials, especially in pre-ataxic mutation carriers close to ataxia onset and patients in early disease stages.
Topics: Humans; Spinocerebellar Ataxias; Seizures; Disease Progression
PubMed: 37592453
DOI: 10.1002/acn3.51875 -
Cells Sep 2020Metastasis formation accounts for the majority of tumor-associated deaths and consists of different steps, each of them being characterized by a distinctive adaptive... (Review)
Review
Metastasis formation accounts for the majority of tumor-associated deaths and consists of different steps, each of them being characterized by a distinctive adaptive phenotype of the cancer cells. Metabolic reprogramming represents one of the main adaptive phenotypes exploited by cancer cells during all the main steps of tumor and metastatic progression. In particular, the metabolism of cancer cells evolves profoundly through all the main phases of metastasis formation, namely the metastatic dissemination, the metastatic colonization of distant organs, the metastatic dormancy, and ultimately the outgrowth into macroscopic lesions. However, the metabolic reprogramming of metastasizing cancer cells has only recently become the subject of intense study. From a clinical point of view, the latter steps of the metastatic process are very important, because patients often undergo surgical removal of the primary tumor when cancer cells have already left the primary tumor site, even though distant metastases are not clinically detectable yet. In this scenario, to precisely elucidate if and how metabolic reprogramming drives acquisition of cancer-specific adaptive phenotypes might pave the way to new therapeutic strategies by combining chemotherapy with metabolic drugs for better cancer eradication. In this review we discuss the latest evidence that claim the importance of metabolic adaptation for cancer progression.
Topics: Disease Progression; Epithelial-Mesenchymal Transition; Female; Humans; Male; Neoplasm Metastasis; Neoplasms
PubMed: 32932943
DOI: 10.3390/cells9092081 -
Clinical Gastroenterology and... Feb 2023Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease... (Review)
Review
BACKGROUND & AIMS
Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic consequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD.
METHODS
A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies.
RESULTS
Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively.
CONCLUSIONS
The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cost-Benefit Analysis; State Medicine; Liver Cirrhosis; Disease Progression
PubMed: 34757199
DOI: 10.1016/j.cgh.2021.10.040 -
Chinese Medical Journal Jun 2023Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Biomarkers; Lung Diseases, Interstitial; Lung; Bronchoalveolar Lavage Fluid; Disease Progression; Prognosis
PubMed: 37130223
DOI: 10.1097/CM9.0000000000002171 -
Acta Ortopedica Mexicana 2020The study of our genome has played an important role in the field of personalized medicine and clinical practice becoming a useful tool to assist the medical community... (Review)
Review
INTRODUCTION
The study of our genome has played an important role in the field of personalized medicine and clinical practice becoming a useful tool to assist the medical community in the early diagnosis and treatment of countless diseases; osteoarthritis (OA) is a complex chronic degenerative joint disease, despite the high prevalence of this disease and its great impact on public health, little is currently known about its etiology and risk of progression. The purpose of this review is to show the advances in genetics in the study of osteoartrosis.
METHODS
The present is a review of the literature of the different aspects in which genetics has developed in the study of osteoartrosis, its scopes and its possible impact on prevention and treatment.
CONCLUSION
The identification of a high number of candidate genes confirms the complex nature of the disease, it seems clear that the degree of expression of different genes is altered between an arthrosic patient and a healthy one. A deeper understanding of the link between the entire genome sequence and the association with well-characterized OA phenotypes will enable the development of biomarkers, report the risk of disease progression and allow better guidance of treatments.
Topics: Biomarkers; Disease Progression; Humans; Osteoarthritis; Phenotype
PubMed: 33634639
DOI: No ID Found -
Sensors (Basel, Switzerland) Dec 2023Biomarkers are vital in healthcare as they provide valuable insights into disease diagnosis, prognosis, treatment response, and personalized medicine. They serve as... (Review)
Review
Biomarkers are vital in healthcare as they provide valuable insights into disease diagnosis, prognosis, treatment response, and personalized medicine. They serve as objective indicators, enabling early detection and intervention, leading to improved patient outcomes and reduced costs. Biomarkers also guide treatment decisions by predicting disease outcomes and facilitating individualized treatment plans. They play a role in monitoring disease progression, adjusting treatments, and detecting early signs of recurrence. Furthermore, biomarkers enhance drug development and clinical trials by identifying suitable patients and accelerating the approval process. In this review paper, we described a variety of biomarkers applicable for cancer detection and diagnosis, such as imaging-based diagnosis (CT, SPECT, MRI, and PET), blood-based biomarkers (proteins, genes, mRNA, and peptides), cell imaging-based diagnosis (needle biopsy and CTC), tissue imaging-based diagnosis (IHC), and genetic-based biomarkers (RNAseq, scRNAseq, and spatial transcriptomics).
Topics: Humans; Neoplasms; Prognosis; Biomarkers; Disease Progression; Gene Expression Profiling
PubMed: 38202898
DOI: 10.3390/s24010037 -
Scientific Reports May 2023Systemic sclerosis is a rare connective tissue disease; and interstitial lung disease (SSc-ILD) is associated with significant morbidity and mortality. There are no...
Systemic sclerosis is a rare connective tissue disease; and interstitial lung disease (SSc-ILD) is associated with significant morbidity and mortality. There are no clinical, radiologic features, nor biomarkers that identify the specific time when patients are at risk for progression at which the benefits from treatment outweigh the risks. Our study aimed to identify blood protein biomarkers associated with progression of interstitial lung disease in patients with SSc-ILD using an unbiased, high-throughput approach. We classified SSc-ILD as progressive or stable based on change in forced vital capacity over 12 months or less. We profiled serum proteins by quantitative mass spectrometry and analyzed the association between protein levels and progression of SSc-ILD via logistic regression. The proteins associated with at a p value of < 0.1 were queried in the ingenuity pathway analysis (IPA) software to identify interaction networks, signaling, and metabolic pathways. Through principal component analysis, the relationship between the top 10 principal components and progression was evaluated. Unsupervised hierarchical clustering with heatmapping was done to define unique groups. The cohort consisted of 72 patients, 32 with progressive SSc-ILD and 40 with stable disease with similar baseline characteristics. Of a total of 794 proteins, 29 were associated with disease progression. After adjusting for multiple testing, these associations did not remain significant. IPA identified five upstream regulators that targeted proteins associated with progression, as well as a canonical pathway with a higher signal in the progression group. Principal component analysis showed that the ten components with the highest Eigenvalues represented 41% of the variability of the sample. Unsupervised clustering analysis revealed no significant heterogeneity between the subjects. We identified 29 proteins associated with progressive SSc-ILD. While these associations did not remain significant after accounting for multiple testing, some of these proteins are part of pathways relevant to autoimmunity and fibrogenesis. Limitations included a small sample size and a proportion of immunosuppressant use in the cohort, which could have altered the expression of inflammatory and immunologic proteins. Future directions include a targeted evaluation of these proteins in another SSc-ILD cohort or application of this study design to a treatment naïve population.
Topics: Humans; Lung Diseases, Interstitial; Scleroderma, Systemic; Immunosuppressive Agents; Biomarkers; Disease Progression; Lung
PubMed: 37244972
DOI: 10.1038/s41598-023-35840-y -
American Journal of Nephrology 2018
Topics: Disease Progression; Europe; Humans; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
PubMed: 30347387
DOI: 10.1159/000493326