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Annals of Internal Medicine Aug 2019The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear.
PURPOSE
To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults.
DATA SOURCES
PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists.
STUDY SELECTION
English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease.
DATA EXTRACTION
Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.
DATA SYNTHESIS
Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence).
LIMITATIONS
Suboptimal quality and certainty of evidence.
CONCLUSION
Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke.
PRIMARY FUNDING SOURCE
None.
Topics: Cardiovascular Diseases; Cause of Death; Coronary Disease; Diet, Healthy; Dietary Supplements; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke; United States
PubMed: 31284304
DOI: 10.7326/M19-0341 -
Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
Journal of Neurology Sep 2021Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment... (Review)
Review
BACKGROUND
Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.
METHODS
A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.
RESULTS
Differences in neurofilament light between relapsing-remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.
CONCLUSIONS
Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.
Topics: Biomarkers; Humans; Intermediate Filaments; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Neurofilament Proteins
PubMed: 32447549
DOI: 10.1007/s00415-020-09917-x -
Genes Apr 2024Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
METHODS
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
RESULTS
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
DISCUSSION
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurofilament Proteins; Biomarkers; Intermediate Filaments; Prognosis
PubMed: 38674431
DOI: 10.3390/genes15040496 -
Frontiers in Cardiovascular Medicine 2023Hypertrophic cardiomyopathy (HCM) is recognized as the most prevalent form of genetic cardiomyopathy, and recent investigations have shed light on the existence of sex... (Review)
Review
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is recognized as the most prevalent form of genetic cardiomyopathy, and recent investigations have shed light on the existence of sex disparities in terms of clinical presentation, disease progression, and outcomes.
OBJECTIVES
This study aimed to systematically review the literature and perform a meta-analysis to comprehensively compare the clinical outcomes between female and male patients with HCM.
METHODS
A thorough search was conducted in databases including PubMed, Embase, Cochrane Library, and Web of Science, encompassing literature from inception until June 2023. The primary endpoints examined were: (1) all-cause mortality; (2) an arrhythmic endpoint comprising sudden cardiac death (SCD), sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and (3) a composite endpoint incorporating either (1) or (2), in addition to hospitalization for heart failure or cardiac transplantation. Pooled estimates were derived using a random-effects meta-analysis model.
RESULTS
The analysis encompassed a total of 29 observational studies, involving 44,677 patients diagnosed with HCM, of which 16,807 were female. Baseline characteristics revealed that the female group exhibited an advanced age [55.66 ± 0.04 years vs. 50.38 ± 0.03 years, pooled mean difference (MD) = 0.31, 95% CI: 0.22-0.40, = 0.000, = 88.89%], a higher proportion of New York Heart Association class III/IV patients [pooled odds ratio (OR) = 1.94, 95% CI: 1.55-2.43, = 0.000, = 85.92%], and a greater prevalence of left ventricular outflow tract gradient greater than or equal to 30 mmHg (pooled OR = 1.48, 95% CI: 1.27-1.73, = 0.000, = 68.88%) compared to the male group. The female group were more likely to have a positive genetic test (pooled OR = 1.27, 95% CI: 1.08-1.48, = 0.000, = 42.74%) and to carry the myosin heavy chain beta 7 mutation (pooled OR = 1.26, 95% CI: 1.04-1.54, = 0.020, = 0.00%) compared to the male group. Female sex exhibited a significant association with increased risks of all-cause mortality (pooled OR = 1.62, 95% CI: 1.38-1.89, = 0.000, = 72.78%) and the composite endpoint (pooled OR = 1.47, 95% CI: 1.20-1.79, = 0.000, = 84.96%), while no substantial difference was observed in the arrhythmic endpoint (pooled OR = 1.08, 95% CI: 0.87-1.34, = 0.490, = 55.48%).
CONCLUSIONS
The present findings suggest that female patients with HCM tend to experience poorer clinical outcomes. It is imperative to critically reevaluate disease definitions and enhance awareness to mitigate delays in the diagnosis and treatment of HCM in women, thereby fostering equitable healthcare practices.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42023431881).
PubMed: 38116536
DOI: 10.3389/fcvm.2023.1252266 -
Neurology. Clinical Practice Aug 2021There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose... (Review)
Review
BACKGROUND
There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose of this review is to evaluate the clinical utility of blood-based biomarkers in patients with SMA.
METHODS
A systematic review of MEDLINE, DARE, PEDro, PsycINFO, Cochrane Database, LILACS, OTSeeker, SpeechBITE, CINAHL, Scopus, Science Direct, clinicaltrial.gov, OpenGrey, and Google Scholar was performed with the last search data of June 30, 2019.
RESULTS
Survival motor neuron (SMN)-related biomarkers showed an important interpatient and cell variability with a wide overlap between SMA phenotypes and healthy controls. Several plasma protein analytes correlated with motor scores; however, validation studies are needed to rule out false positives. DNA methylation analysis distinguished between patients with mild/moderate SMA and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) levels increased with disease severity and declined considerably after nusinersen treatment.
CONCLUSION
There is no sufficient evidence to support the clinical utility of SMN-related biomarkers to predict disease severity in SMA. pNF-H appears to be a promising biomarker of disease activity and treatment effect in SMA. Further studies should include longitudinal assessments of patients with SMA across functional groups and comparisons with age-matched healthy controls to evaluate the stability of putative biomarkers over time and in response to SMA therapeutics. PROSPERO registration: CRD42019139050.
PubMed: 34484951
DOI: 10.1212/CPJ.0000000000000872 -
PloS One 2016To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other neurological diseases, and are of possible use in ALS.
OBJECTIVE
The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS.
METHODS
A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed.
RESULTS
Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011).
CONCLUSION
NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Neurofilament Proteins
PubMed: 27732645
DOI: 10.1371/journal.pone.0164625 -
World Neurosurgery Nov 2015Intracranial aneurysms (IAs) remain a devastating clinical challenge, and the pathogenesis of IA formation and progression continues to be unclear. Biomarker analysis... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Intracranial aneurysms (IAs) remain a devastating clinical challenge, and the pathogenesis of IA formation and progression continues to be unclear. Biomarker analysis can help us understand IA development. The authors performed a systematic review of current literature on genetic and serum biomarkers for IAs in an attempt to identify diagnostic/prognostic factors for ruptured and unruptured aneurysms.
METHODS
All relevant studies on PubMed that reported blood/cerebrospinal fluid (CSF) biomarkers and genes that regulate biomarker levels for IAs were assessed for whether the biomarkers/genes studied correlated with IA formation and rupture.
RESULTS
Thirty-three studies were reviewed. IAs are associated with an increase in levels of immunologic markers, particularly complement C3 and C9, immunoglobulins IgG and IgM, M1/M2 macrophages, monocytes, and B and T lymphocytes; increase in blood and CSF levels of adhesion molecules; selectins found on vascular endothelium, platelets, and leukocytes; doubled ratios of elastase-to-alpha-1-antitrypsin as controls; elevated levels of neurofilament heavy chain SM135 and S-100 post rupture; and locus 19q13 with many candidate genes.
CONCLUSION
Though the pathophysiology of the disease remains unclear, the current literature supports the role of inflammatory and cell adhesion molecules, enzymes and hormones that effect cerebral vasculature, and other cerebral proteins related to brain and vascular damage in both the formation and progression to rupture of IAs. Future investigations are needed to validate results from previous studies and identify new diagnostic/prognostic biomarkers of IAs.
Topics: Aneurysm, Ruptured; Animals; Biomarkers; Humans; Intracranial Aneurysm; Prognosis
PubMed: 26117089
DOI: 10.1016/j.wneu.2015.06.034 -
Journal of Controlled Release :... Jul 2015Digestive tract tumors are among the most common and deadliest malignancies worldwide, mainly due to late diagnosis and lack of efficient therapeutics. Current... (Review)
Review
Digestive tract tumors are among the most common and deadliest malignancies worldwide, mainly due to late diagnosis and lack of efficient therapeutics. Current treatments essentially rely on surgery associated with (neo)adjuvant chemotherapy agents. Despite an upfront response, conventional drugs often fail to eliminate highly aggressive clones endowed with chemoresistant properties, which are responsible for tumor recurrence and disease dissemination. Synthetic drugs also present severe adverse systemic effects, hampering the administration of biologically effective dosages. Nanoencapsulation of chemotherapeutic agents within biocompatible polymeric or lipid matrices holds great potential to improve the pharmacokinetics and efficacy of conventional chemotherapy while reducing systemic toxicity. Tagging nanoparticle surfaces with specific ligands for cancer cells, namely monoclonal antibodies or antibody fragments, has provided means to target more aggressive clones, further improving the selectivity and efficacy of nanodelivery vehicles. In fact, over the past twenty years, significant research has translated into a wide array of guided nanoparticles, providing the molecular background for a new generation of intelligent and more effective anti-cancer agents. Attempting to bring awareness among the medical community to emerging targeted nanopharmaceuticals and foster advances in the field, we have conducted a systematic review about this matter. Emphasis was set on ongoing preclinical and clinical trials for liver, colorectal, gastric and pancreatic cancers. To the best of our knowledge this is the first systematic and integrated overview on this field. Using a specific query, 433 abstracts were gathered and narrowed to 47 manuscripts when matched against inclusion/exclusion criteria. All studies showed that active targeting improves the effectiveness of the nanodrugs alone, while lowering its side effects. The main focus has been on hepatocarcinomas, mainly by exploring glycans as homing molecules. Other ligands such as peptides/small proteins and antibodies/antibody fragments, with affinity to either tumor vasculature or tumor cells, have also been widely and successfully applied to guide nanodrugs to gastrointestinal carcinomas. Conversely, few solutions have been presented for pancreatic tumors. To this date only three nanocomplexes have progressed beyond pre-clinical stages: i) PK2, a galactosamine-functionalized polymeric-DOX formulation for hepatocarcinomas; ii) MCC-465, an anti-(myosin heavy chain a) immunoliposome for advanced stage metastatic solid tumors; and iii) MBP-426, a transferrin-liposome-oxaliplatin conjugate, also for advanced stage tumors. Still, none has been approved for clinical use. However, based on the high amount of pre-clinical studies showing enthusiastic results, the number of clinical trials is expected to increase in the near future. A more profound understanding about the molecular nature of chemoresistant clones and cancer stem cell biology will also contribute to boost the field of guided nanopharmacology towards more effective solutions.
Topics: Animals; Antineoplastic Agents; Digestive System Neoplasms; Humans; Nanoparticles
PubMed: 25957905
DOI: 10.1016/j.jconrel.2015.05.003 -
Frontiers in Oncology 2021Many diseases are accompanied by changes in certain biochemical indicators called biomarkers in cells or tissues. A variety of biomarkers, including proteins, nucleic... (Review)
Review
Many diseases are accompanied by changes in certain biochemical indicators called biomarkers in cells or tissues. A variety of biomarkers, including proteins, nucleic acids, antibodies, and peptides, have been identified. Tumor biomarkers have been widely used in cancer risk assessment, early screening, diagnosis, prognosis, treatment, and progression monitoring. For example, the number of circulating tumor cell (CTC) is a prognostic indicator of breast cancer overall survival, and tumor mutation burden (TMB) can be used to predict the efficacy of immune checkpoint inhibitors. Currently, clinical methods such as polymerase chain reaction (PCR) and next generation sequencing (NGS) are mainly adopted to evaluate these biomarkers, which are time-consuming and expansive. Pathological image analysis is an essential tool in medical research, disease diagnosis and treatment, functioning by extracting important physiological and pathological information or knowledge from medical images. Recently, deep learning-based analysis on pathological images and morphology to predict tumor biomarkers has attracted great attention from both medical image and machine learning communities, as this combination not only reduces the burden on pathologists but also saves high costs and time. Therefore, it is necessary to summarize the current process of processing pathological images and key steps and methods used in each process, including: (1) pre-processing of pathological images, (2) image segmentation, (3) feature extraction, and (4) feature model construction. This will help people choose better and more appropriate medical image processing methods when predicting tumor biomarkers.
PubMed: 34900711
DOI: 10.3389/fonc.2021.763527