Dataset Information

Lipid Profile in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Studies have investigated the lipid profile in amyotrophic lateral sclerosis (ALS), including the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and higher low-density lipoprotein (LDL), and the associations with mortality of ALS, but the results were inconsistent. Therefore, we conducted this meta-analysis to systematically answer this unsolved question. Methods: We searched all the related studies that probed into the association between serum lipid levels and ALS based on PubMed, EMBASE, and Cochrane library from January 1990 to July 2020. The quality of the included studies was evaluated by using the Newcastle-Ottawa Scale (NOS). All the statistical analyses of this meta-analysis were performed using the Stata version 12.0 software. Results: Fourteen studies with a total of 3,291 ALS patients and 3,367 controls were included. Among them, 10 studies compared the lipid profile between ALS patients and controls. The results indicated that compared with controls, ALS patients from both Europe and Asia had lower levels of TG and HDL, but the levels of TC and LDL were higher in ALS patients from Europe. However, after systemic analyses, the altered TC level was significant only in Asian ALS patients; the differences of other lipids were not significant. Concerning the effect of lipid profile on mortality of ALS, analyses of four cohort studies showed that the levels of all lipids were not associated with overall mortality in ALS. Conclusion: The results of the present study showed that Asian ALS patients had lower TC levels than controls, and the levels of all lipids were not associated with mortality of ALS.

SUBMITTER: Liu J

PROVIDER: S-EPMC7593382 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lipid Profile in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Liu Jiao J Luo Xiaoyue X Chen Xueping X Shang Huifang H

Frontiers in neurology 20201015

<b>Background:</b> Studies have investigated the lipid profile in amyotrophic lateral sclerosis (ALS), including the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and higher low-density lipoprotein (LDL), and the associations with mortality of ALS, but the results were inconsistent. Therefore, we conducted this meta-analysis to systematically answer this unsolved question. <b>Methods:</b> We searched all the related studies that probed into the association ...[more]

PMID: 33178110

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Project description:Background: The effect of herbal medicine (HM) on amyotrophic lateral sclerosis (ALS) is controversial. Clinical trials investigating HMs continue; however, the use of HM is still questioned. We aimed to systematically review the literature pertaining to the effects and safety of HM in ALS. Methods: Randomised controlled trials (RCTs) that investigated the efficacy of HMs in ALS patients compared to any types of controls were identified. Nine databases and six registers were searched from their inception dates to 25 March 2022. Per the PRISMA guidelines, trials were identified and extracted. The risk of bias was evaluated using the Cochrane's tool. Certainty of evidence was assessed as per the GRADE criteria. Forest plots were constructed to assess the effect size and corresponding 95% CIs using fixed-effect models, and random-effect models were employed when required. The primary outcome was the activity limitation measured by validated tools, such as the revised ALS Functional Rating Scale. Results: Twenty studies (N = 1,218) were eligible. Of these, only five studies were double-blinded, and two were placebo-controlled. Fourteen HMs (fifty-one single botanicals) were involved; Astragalus mongholicus Bunge, Atractylodes macrocephala Koidz., and Glycyrrhiza glabra L. were commonly used in nine, eight, and six trials, respectively. For delaying activity limitation, Jiweiling injection (MD, 2.84; 95% CI, 1.21 to 4.46; p = 0.0006) and Shenmai injection (SMD, 1.07; 0.69 to 1.45; p < 0.00001) were significantly more efficacious than Riluzole, but the evidence was low quality. For ameliorating motor neuron loss, Jiweiling injection [right abductor pollicis brevis (APB): MD, 32.42; 7.91 to 56.93; p = 0.01 and left APB: MD, 34.44; 12.85 to 56.03; p = 0.002] was favoured, but the evidence was very low quality. Nine studies reported one hundred and twenty-three adverse events, twenty-six of which occurred in the treatment groups and ninety-seven in the control groups. Conclusion: Very low to low quality of evidence suggests that HMs seem to produce superior treatment responses for ALS without increased risk of adverse events. Additional studies with homogeneous participants, reduced methodological issues, and more efficient outcome measures are required to provide confirmatory evidence. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021277443.

Project description:Interventions targeting mitochondrial dysfunction have the potential to extend survival in preclinical models of amyotrophic lateral sclerosis. The aim of this systematic review was to assess the efficacy of targeting mitochondria as a potential therapeutic target in amyotrophic lateral sclerosis. Preclinical studies written in the English language were identified with no restrictions on publication date from PubMed, Medline and EMBASE databases. All studies adopting interventions targeting mitochondria to treat amyotrophic lateral sclerosis in genetic or drug-induced organism models were considered for inclusion. A total of 76 studies were included in the analysis. Survival data were extracted, and the meta-analysis was completed in RevMan 5 software. We show that targeting mitochondrial dysfunction in amyotrophic lateral sclerosis results in a statistically significant improvement in survival (Z = 5.31; P<0.00001). The timing of administration of the intervention appears to affect the improvement in survival, with the greatest benefit occurring for interventions given prior to disease onset. Interventions at other time points were not significant, although this is likely to be secondary to a lack of publications examining these timepoints. The quality score had no impact on efficacy, and publication bias revealed an overestimation of the effect size, owing to one outlier study; excluding this led to the recalculated effect size changing from 5.31 to 3.31 (P<0.00001). The extant preclinical literature indicates that targeting mitochondrial dysfunction may prolong survival in amyotrophic lateral sclerosis, particularly if the intervention is administered early. A limitation of current research is a significant bias towards models based on superoxide dismutase 1, with uncertainty about generalisability to amyotrophic lateral sclerosis with an underlying TAR DNA binding protein 43 proteinopathy. However, further mechanistic research is clearly warranted in this field.

Project description:Oxidative stress has been reported to be involved in the onset and development of amyotrophic lateral sclerosis (ALS). Data from clinical studies have highlighted increased peripheral blood oxidative stress markers in patients with ALS, but results are inconsistent. Therefore, we quantitatively pooled data on levels of blood oxidative stress markers in ALS patients from the literature using a meta-analytic technique. A systematic search was performed on PubMed and Web of Science, and we included studies analyzing blood oxidative stress marker levels in patients with ALS and normal controls. We included 41 studies with 4,588 ALS patients and 6,344 control subjects, and 15 oxidative stress marker levels were subjected to random-effects meta-analysis. The results demonstrated that malondialdehyde (Hedges' g, 1.168; 95% CI, 0.812 to 1.523; P < 0.001), 8-hydroxyguanosine (Hedges' g, 2.194; 95% CI, 0.554 to 3.835; P = 0.009), and Advanced Oxidation Protein Product (Hedges' g, 0.555; 95% CI, 0.317 to 0.792; P < 0.001) levels were significantly increased in patients with ALS when compared with control subjects. Uric acid (Hedges' g, -0.798; 95% CI, -1.117 to -0.479; P < 0.001) and glutathione (Hedges' g, -1.636; 95% CI, -3.020 to -0.252; P = 0.02) levels were significantly reduced in ALS patients. In contrast, blood Cu, superoxide dismutase, glutathione peroxidase, ceruloplasmin, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, coenzyme-Q10, and transferrin levels were not significantly different between cases and controls. Taken together, our results showed significantly increased blood levels of 8-hydroxyguanosine, malondialdehyde, and Advanced Oxidation Protein Product and decreased glutathione and uric acid levels in the peripheral blood of ALS patients. This meta-analysis helps to clarify the oxidative stress marker profile in ALS patients, supporting the hypothesis that oxidative stress is a central component underpinning ALS pathogenesis.

Project description:BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a highly progressive and debilitating neurodegenerative disease, which usually leads to the death of affected individuals within a few years after the onset of symptoms. ALS is currently incurable and very little is known about its pathophysiology. Finding validated biomarkers will help us to advance our understanding of ALS etiology and find better strategies for early diagnosis and management of the disease. The main aim of the present systematic review is to evaluate the concentration of 11 frequently reported biomarkers for ALS in peripheral blood and CSF of patients diagnosed with ALS compared with controls. METHODS:This systematic review protocol has been established according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 guideline. We will include all types of observational studies with human subjects that investigated the concentrations of intended biomarkers (amyloid beta (Aβ-42), tau and phosphorylated tau (p-Tau), neurofilaments, S100β, cystatin C, progranulin (PGRN), glial fibrillary acidic protein (GFAP), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), TAR DNA-binding protein-43 (TDP43), YKL-40, and CHIT1 in CSF or peripheral blood of ALS patients for initial assessment. Also, we will include case series with a minimum of 10 cases and clinical trials which have measured baseline biomarker levels. Case studies, case reports, reviews, letters, and animal and in vitro studies will be excluded. Multiple electronic databases including Cochrane Library, MEDLINE (PubMed), ISI Web of Science, and EMBASE will be searched to find all eligible articles published since 1980. No language restriction will be applied. All titles and abstracts retrieved by searching information sources will be evaluated independently by two authors against the eligibility criteria. The following information will be extracted from each included study by two independent authors: bibliographic details (first author, study title, year of publication, country), demographics and clinical information (number of patients and controls, type of ALS and controls, study design, age, gender, specimen, biomarkers levels, ALS functional rating scale Revised (ALSFRS-R), duration of disease), and measurements (method, value type, biomarkers levels). We will use the extracted mean and standard deviation (SD) of biomarkers concentrations to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). The primary outcome measures are the mean difference of biomarker levels between ALS patients and controls, different types of ALS, and ALS patients with genetic mutations. DISCUSSION:We will systematically review the literature and analyze studies of biomarker level in CSF and peripheral blood of patients with ALS and controls. The results will help us to identify biomarkers with possible diagnostic and prognostic value. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42017078127.

Dataset Information

Lipid Profile in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Publications

Lipid Profile in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

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