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Annals of Internal Medicine May 2020Biomarker accuracy for Alzheimer disease (AD) is uncertain.
BACKGROUND
Biomarker accuracy for Alzheimer disease (AD) is uncertain.
PURPOSE
To summarize evidence on biomarker accuracy for classifying AD in older adults with dementia.
DATA SOURCES
Electronic bibliographic databases (searched from January 2012 to November 2019 for brain imaging and cerebrospinal fluid [CSF] tests and from inception to November 2019 for blood tests), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.
STUDY SELECTION
English-language studies evaluating the accuracy of brain imaging, CSF testing, or blood tests for distinguishing neuropathologically defined AD from non-AD among older adults with dementia. Studies with low or medium risk of bias were analyzed.
DATA EXTRACTION
Two reviewers rated risk of bias. One extracted data; the other verified accuracy.
DATA SYNTHESIS
Fifteen brain imaging studies and 9 CSF studies met analysis criteria. Median sensitivity and specificity, respectively, were 0.91 and 0.92 for amyloid positron emission tomography (PET), 0.89 and 0.74 for F-labeled fluorodeoxyglucose (F-FDG) PET, 0.64 and 0.83 for single-photon emission computed tomography, and 0.91 and 0.89 for medial temporal lobe atrophy on magnetic resonance imaging (MRI). Individual CSF biomarkers and ratios had moderate sensitivity (range, 0.62 to 0.83) and specificity (range, 0.53 to 0.69); in the few direct comparisons, β-amyloid 42 (Aβ42)/phosphorylated tau (p-tau) ratio, total tau (t-tau)/Aβ42 ratio, and p-tau appeared more accurate than Aβ42 and t-tau alone. Single studies suggested that amyloid PET, F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation.
LIMITATIONS
Studies were small, biomarker cut points and neuropathologic AD were inconsistently defined, and methods with uncertain applicability to typical clinical settings were used. Few studies directly compared biomarkers, assessed test combinations, evaluated whether biomarkers improved classification accuracy when added to clinical evaluation, or reported harms.
CONCLUSION
In methodologically heterogeneous studies of uncertain applicability to typical clinical settings, amyloid PET, F-FDG PET, and MRI were highly sensitive for neuropathologic AD. Amyloid PET, F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).
Topics: Aged; Alzheimer Disease; Biomarkers; Brain; Dementia; Humans; Magnetic Resonance Imaging; Reproducibility of Results
PubMed: 32340038
DOI: 10.7326/M19-3888 -
International Journal of Molecular... Mar 2021Allograft ischemia during liver transplantation (LT) adversely affects the function of mitochondria, resulting in impairment of oxidative phosphorylation and compromised... (Meta-Analysis)
Meta-Analysis
Allograft ischemia during liver transplantation (LT) adversely affects the function of mitochondria, resulting in impairment of oxidative phosphorylation and compromised post-transplant recovery of the affected organ. Several preservation methods have been developed to improve donor organ quality; however, their effects on mitochondrial functions have not yet been compared. This study aimed to summarize the available data on mitochondrial effects of graft preservation methods in preclinical models of LT. Furthermore, a network meta-analysis was conducted to determine if any of these treatments provide a superior benefit, suggesting that they might be used on humans. A systematic search was conducted using electronic databases (EMBASE, MEDLINE (via PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science) for controlled animal studies using preservation methods for LT. The ATP content of the graft was the primary outcome, as this is an indicator overall mitochondrial function. Secondary outcomes were the respiratory activity of mitochondrial complexes, cytochrome c and aspartate aminotransferase (ALT) release. Both a random-effects model and the SYRCLE risk of bias analysis for animal studies were used. After a comprehensive search of the databases, 25 studies were enrolled in the analysis. Treatments that had the most significant protective effect on ATP content included hypothermic and subnormothermic machine perfusion (HMP and SNMP) (MD = -1.0, 95% CI: (-2.3, 0.3) and MD = -1.1, 95% CI: (-3.2, 1.02)), while the effects of warm ischemia (WI) without cold storage (WI) and normothermic machine perfusion (NMP) were less pronounced (MD = -1.8, 95% CI: (-2.9, -0.7) and MD = -2.1 MD; CI: (-4.6; 0.4)). The subgroup of static cold storage (SCS) with shorter preservation time (< 12 h) yielded better results than SCS ≥ 12 h, NMP and WI, in terms of ATP preservation and the respiratory capacity of complexes. HMP and SNMP stand out in terms of mitochondrial protection when compared to other treatments for LT in animals. The shorter storage time at lower temperatures, together with the dynamic preservation, provided superior protection for the grafts in terms of mitochondrial function. Additional clinical studies on human patients including marginal donors and longer ischemia times are needed to confirm any superiority of preservation methods with respect to mitochondrial function.
Topics: Animals; Delayed Graft Function; Humans; Liver Transplantation; Mitochondria, Liver; Organ Preservation; Warm Ischemia
PubMed: 33802177
DOI: 10.3390/ijms22062816 -
JID Innovations : Skin Science From... Jul 2022As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous... (Review)
Review
As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.
PubMed: 35620703
DOI: 10.1016/j.xjidi.2022.100126 -
In Vivo (Athens, Greece) 2020The insulin-like growth factor bioregulation system is implicated in cancer biology. Herein, we aim to review the evidence on the expression of the insulin-like growth... (Review)
Review
BACKGROUND/AIM
The insulin-like growth factor bioregulation system is implicated in cancer biology. Herein, we aim to review the evidence on the expression of the insulin-like growth factor 1 and 2 (IGF1 and IGF2), their receptors (IGF-Rs) and IGF-binding proteins (IGFBPs) in thyroid tissue and their possible association with benign and malignant thyroid nodular diseases.
MATERIALS AND METHODS
We systematically reviewed Pubmed and Scopus databases up to May 2020. A total of 375 articles were retrieved and analyzed.
RESULTS
Among 375 articles, 45 were included in this systematic review study. IGF1 was investigated in 31 studies, IGF2 in 1, IGF1 receptor in 15 and IGF-binding proteins in 13 articles. IGF1 expression in humans was dependent on the number and compound of benign nodules as well as the method of measurement. In differentiated thyroid carcinoma, a positive correlation between IGF1 and immunohistological stage was documented in some studies while in others only a positive trend was observed. IGF-1R and IGFBPs expression was higher in malignant rather than benign lesions. There was only a positive trend for increased IGF2 expression in malignancy, while IGFBPs were in most studies statistically increased in various cancer types compared to benign nodular disease.
CONCLUSION
The present data demonstrate that in most studies there is statistically positive expression of IGF-1 and less of IGF-2 in thyroid cancer compared to normal thyroid tissue.
Topics: Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Phosphorylation; Receptor, IGF Type 1; Signal Transduction; Thyroid Neoplasms
PubMed: 33144411
DOI: 10.21873/invivo.12141 -
Journal of Neuromuscular Diseases 2021Leigh syndrome (LS) is the most frequent paediatric clinical presentation of mitochondrial disease. The clinical phenotype of LS is highly heterogeneous. Though...
BACKGROUND
Leigh syndrome (LS) is the most frequent paediatric clinical presentation of mitochondrial disease. The clinical phenotype of LS is highly heterogeneous. Though historically the treatment for LS is largely supportive, new treatments are on the horizon. Due to the rarity of LS, large-scale interventional studies are scarce, limiting dissemination of information of therapeutic options to the wider scientific and clinical community.
OBJECTIVE
We conducted a systematic review of pharmacological therapies of LS following the guidelines for FAIR-compliant datasets.
METHODS
We searched for interventional studies within Clincialtrials.gov and European Clinical trials databases. Randomised controlled trials, observational studies, case reports and case series formed part of a wider MEDLINE search.
RESULTS
Of the 1,193 studies initially identified, 157 met our inclusion criteria, of which 104 were carried over into our final analysis. Treatments for LS included very few interventional trials using EPI-743 and cysteamine bitartrate. Wider literature searches identified case series and reports of treatments repleting glutathione stores, reduction of oxidative stress and restoration of oxidative phosphorylation.
CONCLUSIONS
Though interventional randomised controlled trials have begun for LS, the majority of evidence remains in case reports and case series for a number of treatable genes, encoding cofactors or transporter proteins of the mitochondria. Our findings will form part of the international expert-led Solve-RD efforts to assist clinicians initiating treatments in patients with treatable variants of LS.
Topics: Child; Humans; Leigh Disease; Mitochondria; Phenotype
PubMed: 34308912
DOI: 10.3233/JND-210715 -
Evidence-based Complementary and... 2019At present, the prevention and treatment of cardiovascular disease in the world are facing severe challenges. Xinmailong injection, which is derived from the animal... (Review)
Review
BACKGROUND
At present, the prevention and treatment of cardiovascular disease in the world are facing severe challenges. Xinmailong injection, which is derived from the animal medicine , has certain advantages in the clinical treatment of cardiovascular disease. This study systematically evaluated the basic research reports of Xinmailong Injection on cardiovascular disease and made its pharmacological mechanisms more clear.
METHODS
Basic research reports on the intervention mechanisms of Xinmailong Injection on cardiovascular disease in PubMed, EMBASE, Cochrane Library (No. 2, 2019), CNKI, Wan Fang, and VIP databases were searched. The search time limit was from the establishment of the database to February 2019. The literature was screened according to inclusion and exclusion criteria, and then the data were extracted and a descriptive analysis of the pharmacological mechanisms of Xinmailong Injection on cardiovascular disease was performed.
RESULTS
Finally, twenty-two basic research reports were included. The intervention mechanisms of Xinmailong Injection on cardiovascular disease mainly includes the following: inhibiting oxidative stress and inflammatory reaction; regulating autophagy; promoting Ca influx by activating excitability of excitation-contraction coupling (ECC); inhibiting overexpressions of transforming growth factor-1 (TGF-1) and connective tissue growth factor (CTGF) to regulate the dynamic balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs); inhibiting the phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (AKT), and glycogen synthase kinase 3 (GSK3) proteins and overexpression of the downstream transcription factor GATA4 in the nucleus; regulating vascular endothelial factors and so on.
CONCLUSIONS
Xinmailong Injection can protect cardiomyocytes and maintain the normal function of the heart in various ways, thus effectively preventing the development of cardiovascular disease. Therefore, Xinmailong Injection has great potential for clinical application, and more basic researches need to be carried out to explore the medicinal value of Xinmailong Injection.
PubMed: 32454845
DOI: 10.1155/2019/8512405 -
European Stroke Journal Jun 2024There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the...
INTRODUCTION
There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the levels of four biomarkers [β-amyloids (Aβ42 and Aβ40), total tau (tau) and phosphorylated tau (p-tau)] in CAA patients compared to healthy controls (HC) and patients with Alzheimer Disease (AD).
PATIENTS AND METHODS
A systematic review and meta-analysis of published studies, including also a 5 year single-center cohort study, with available data on CSF and plasma biomarkers in symptomatic sporadic CAA versus HC and AD was conducted. Biomarkers' comparisons were investigated using random-effects models based on the ratio of mean (RoM) biomarker concentrations. RoM < 1 and RoM > 1 indicate lower and higher biomarker concentration in CAA compared to another population, respectively.
RESULTS
We identified nine cohorts, comprising 327 CAA patients (mean age: 71 ± 5 years; women: 45%) versus 336 HC (mean age: 65 ± 5 years; women: 45%) and 384 AD patients (mean age: 68 ± 3 years; women: 53%) with available data on CSF biomarkers. CSF Aβ42 levels [RoM: 0.47; 95% CI: 0.36-0.62; < 0.0001], Aβ40 levels [RoM: 0.70; 95% CI: 0.63-0.79; < 0.0001] and the ratio Aβ42/Aβ40 [RoM: 0.62; 95% CI: 0.39-0.98; = 0.0438] differentiated CAA from HC. CSF Aβ40 levels [RoM: 0.73; 95% CI: 0.64-0.83; = 0.0003] differentiated CAA from AD. CSF tau and p-tau levels differentiated CAA from HC [RoM: 1.71; 95% CI: 1.41-2.09; = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; < 0.0001, respectively]. Plasma Aβ42 [RoM: 1.14; 95% CI: 0.89-1.45; = 0.2079] and Aβ40 [RoM: 1.07; 95% CI: 0.91-1.25; = 0.3306] levels were comparable between CAA and HC.
CONCLUSIONS
CAA is characterized by a distinct CSF biomarker pattern compared to HC and AD. CSF Aβ40 levels are lower in CAA compared to HC and AD, while tau and p-tau levels are higher in CAA compared to HC, but lower in comparison to AD patients.
PubMed: 38869035
DOI: 10.1177/23969873241260538 -
Antioxidants (Basel, Switzerland) Mar 2024The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B,... (Review)
Review
Investigating the Neuroprotective and Cognitive-Enhancing Effects of : A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.
The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.
PubMed: 38671841
DOI: 10.3390/antiox13040393 -
Neural Regeneration Research Dec 2024The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and...
The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers. In the present study, after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease, we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients. A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289 articles. After screening and exclusion, 34 relevant articles were derived for systematic review. Alpha-synuclein, the histopathological hallmark of Parkinson's disease, has been the most investigated Parkinson's disease biomarker in saliva, with oligomeric alpha-synuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls, while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein, and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease. Beyond alpha-synuclein, other biomarkers targeting different molecular pathways have been explored in the saliva of Parkinson's disease patients: total tau, phosphorylated tau, amyloid-β1-42 (pathological protein aggregation biomarkers); DJ-1, heme-oxygenase-1, metabolites (altered energy homeostasis biomarkers); MAPLC-3beta (aberrant proteostasis biomarker); cortisol, tumor necrosis factor-alpha (inflammation biomarkers); DNA methylation, miRNA (DNA/RNA defects biomarkers); acetylcholinesterase activity (synaptic and neuronal network dysfunction biomarkers); Raman spectra, proteome, and caffeine. Despite a few studies investigating biomarkers targeting molecular pathways different from alpha-synuclein in Parkinson's disease, these results should be replicated and observed in studies on larger cohorts, considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes. Although the need for standardization in sample collection and processing, salivary-based biomarkers studies have reported encouraging results, calling for large-scale longitudinal studies and multicentric assessments, given the great molecular potentials and the non-invasive accessibility of saliva.
PubMed: 38595280
DOI: 10.4103/NRR.NRR-D-23-01677 -
Frontiers in Neuroscience 2022Most previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms...
BACKGROUND
Most previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms have not been systematically reviewed. Acupuncture modulates cytokines to attenuate cartilage extracellular matrix degradation and apoptosis, key to the pathogenesis of KOA, but the mechanisms are complex.
OBJECTIVES
The purpose of this study is to assess the efficacy of acupuncture quantitatively and summarily in animal studies of KOA.
METHODS
Nine databases including PubMed, Embase, Web of Science (including Medline), Cochrane library, Scopus, CNKI, Wan Fang, and VIP were searched to retrieve animal studies on acupuncture interventions in KOA published since the inception of the journal. Relevant literature was screened, and information extracted. Meta-analysis was performed using Revman 5.4 and Stata 17.0 software.
RESULTS
The 35 included studies involved 247 animals, half of which were in acupuncture groups and half in model groups. The mean quality level was 6.7, indicating moderate quality. Meta-analysis showed that acupuncture had the following significant effects on cytokine levels in p38MAPK and mitochondrial pathways: (1) p38MAPK pathway: It significantly inhibits p38MAPK, interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), phosphorylated (p)-p38MAPK, matrix metalloproteinase-13 (MMP-13), MMP-1, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMST-5) expression, and significantly increased the expression of collagen II and aggrecan. (2) mitochondrial pathway: It significantly inhibited the expression of Bcl-2-associated X protein (Bax), cysteine protease-3 (caspase-3), caspase-9, and Cytochrome-c (Cyt-c). And significantly increased the expression of B cell lymphocytoma-2 (Bcl-2). In addition, acupuncture significantly reduced chondrocyte apoptosis, Mankin's score (a measure of cartilage damage), and improved cartilage morphometric characteristics.
CONCLUSION
Acupuncture may inhibit cytokine expression in the p38MAPK pathway to attenuate cartilage extracellular matrix degradation, regulate cytokines in the mitochondrial pathway to inhibit chondrocyte apoptosis, and improve cartilage tissue-related phenotypes to delay cartilage degeneration. These findings provide possible explanations for the therapeutic mechanisms and clinical benefits of acupuncture for KOA.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com, identifier INPLASY20 2290125.
PubMed: 36711149
DOI: 10.3389/fnins.2022.1098311