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Tumour Biology : the Journal of the... 2022Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies.
MATERIALS AND METHODS
PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study.
RESULTS
Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features.
CONCLUSION
APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.
Topics: Breast Neoplasms; Cytidine Deaminase; Disease-Free Survival; Female; Humans; Lung Neoplasms; Minor Histocompatibility Antigens; Proportional Hazards Models
PubMed: 36093650
DOI: 10.3233/TUB-211577 -
International Journal of Molecular... Sep 2022Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of... (Review)
Review
Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015-2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.
Topics: Alzheimer Disease; Biomarkers; Humans; Lacrimal Apparatus Diseases; Multiple Sclerosis; Parkinson Disease; Tears
PubMed: 36077520
DOI: 10.3390/ijms231710123 -
Journal of the American Heart... Sep 2022Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular... (Meta-Analysis)
Meta-Analysis
Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol.
Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.
Topics: Anticholesteremic Agents; Apolipoproteins; Cholesterol; Cholesterol, LDL; Dicarboxylic Acids; Double-Blind Method; Ezetimibe; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36073669
DOI: 10.1161/JAHA.122.025551 -
Neuropsychology Review Dec 2023First-degree relatives of individuals with late-onset Alzheimer's disease (LOAD) are at increased risk for developing dementia, yet the associations between family... (Meta-Analysis)
Meta-Analysis Review
First-degree relatives of individuals with late-onset Alzheimer's disease (LOAD) are at increased risk for developing dementia, yet the associations between family history of LOAD and cognitive dysfunction remain unclear. In this quantitative review, we provide the first meta-analysis on the cognitive profile of unaffected first-degree blood relatives of LOAD-affected individuals compared to controls without a family history of LOAD. A systematic literature search was conducted in PsycINFO, PubMed /MEDLINE, and Scopus. We fitted a three-level structural equation modeling meta-analysis to control for non-independent effect sizes. Heterogeneity and risk of publication bias were also investigated. Thirty-four studies enabled us to estimate 218 effect sizes across several cognitive domains. Overall, first-degree relatives (n = 4,086, mean age = 57.40, SD = 4.71) showed significantly inferior cognitive performance (Hedges' g = -0.16; 95% CI, -0.25 to -0.08; p < .001) compared to controls (n = 2,388, mean age = 58.43, SD = 5.69). Specifically, controls outperformed first-degree relatives in language, visuospatial and verbal long-term memory, executive functions, verbal short-term memory, and verbal IQ. Among the first-degree relatives, APOE ɛ4 carriership was associated with more significant dysfunction in cognition (g = -0.24; 95% CI, -0.38 to -0.11; p < .001) compared to non-carriers (g = -0.14; 95% CI, -0.28 to -0.01; p = .04). Cognitive test type was significantly associated with between-group differences, accounting for 65% (R = .6499) of the effect size heterogeneity in the fitted regression model. No evidence of publication bias was found. The current findings provide support for mild but robust cognitive dysfunction in first-degree relatives of LOAD-affected individuals that appears to be moderated by cognitive domain, cognitive test type, and APOE ɛ4.
Topics: Humans; Middle Aged; Alzheimer Disease; Cognition; Cognitive Dysfunction; Cognition Disorders; Neuropsychological Tests; Apolipoproteins E
PubMed: 36057684
DOI: 10.1007/s11065-022-09555-2 -
International Journal of Clinical... 2022Biomarkers are necessary to stratify the risk of diabetic foot ulcers (DFUs). This systematic review and meta-analysis aimed to evaluate the association between the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Biomarkers are necessary to stratify the risk of diabetic foot ulcers (DFUs). This systematic review and meta-analysis aimed to evaluate the association between the lipid profile and apolipoproteins with the risk of DFU.
METHODS
A systematic search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science among adult patients. Cohort and case-control studies were included. Random-effects models were used for meta-analyses, and the effects were expressed as odds ratio (OR) and their 95% confidence intervals (CIs). We evaluated publication bias through Egger's test and funnel plot.
RESULTS
A total of 12 cohort studies and 26 case-control studies were included, with 17076 patients. We found that the higher values of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides, and lipoprotein(a) (Lp(a)) were associated with a higher risk of developing DFU (OR: 1.47, OR: 1.47, OR: 1.5, OR: 1.85, respectively). Otherwise, the lower values of HDL were associated with a higher risk of developing DFU (OR: 0.49). Publication bias was not found for associations between TC, HDL, LDL, or TG and the risk of DFU.
CONCLUSIONS
The high values of LDL, TC, TG, and Lp(a) and low values of HDL are associated with a higher risk of developing DFU. Furthermore, we did not find a significant association for VLDL, ApoA1, ApoB, and ApoB/ApoA1 ratio.
Topics: Adult; Apolipoproteins; Apolipoproteins B; Case-Control Studies; Cholesterol, HDL; Diabetes Mellitus; Diabetic Foot; Humans; Triglycerides
PubMed: 36016824
DOI: 10.1155/2022/5450173 -
Diabetologia Dec 2022Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes.
METHODS
We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence.
RESULTS
We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I=88%, p<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], p=0.05; substantial heterogeneity: I=89%, p<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency.
CONCLUSIONS/INTERPRETATION
Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes.
REGISTRATION
ClinicalTrials.gov NCT04094194.
FUNDING
Diabetes and Nutrition Study Group of the EASD Clinical Practice.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Prospective Studies; Cholesterol, HDL; Cholesterol, LDL; Cholesterol; Obesity; Body Weight; Stroke; Inflammation; Apolipoproteins; Insulins; Randomized Controlled Trials as Topic
PubMed: 36008559
DOI: 10.1007/s00125-022-05760-z -
Journal of Clinical Medicine Aug 2022Dyslipidemia has been linked to breast cancer incidence. The aim of the present meta-analysis was to further investigate the relationship between the serum lipid profile... (Review)
Review
Dyslipidemia has been linked to breast cancer incidence. The aim of the present meta-analysis was to further investigate the relationship between the serum lipid profile and breast cancer risk. Databases such as PubMed, EMBASE, and Web of Sciences were searched up to the end of January 2021 using certain MeSH and non-MeSH keywords and combinations to extract related published articles. Twenty-six prospective studies involving 1,628,871 women, of whom 36,590 were diagnosed with breast cancer during the follow-up period met the inclusion criteria. A negative and significant association was found between the HDL-C level and the risk of breast cancer (relative risk (RR): 0.85, 95% CI: 0.72-0.99, I: 67.6%, = 0.04). In contrast, TG (RR: 1.02, 95% CI: 0.91-1.13, I: 54.2%, = 0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90-1.06, I: 67.2%, = 0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70-1.30, I: 83.5%, = 0.78) and LDL-C (RR: 0.93, 95% CI: 0.79-1.09, I: 0%, = 0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, breast cancer risk was positively correlated with TC (RR: 1.05, 95% CI: 1.01-1.10). Similarly, TG was significantly related to breast cancer development after adjustment for baseline lipids (RR: 0.92, 95% CI: 0.85-0.99) and race (any races mentioned in each study) (RR: 1.80, 95% CI: 1.22-2.65). In the present meta-analysis, HDL-C was inversely related to breast cancer risk. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence that low HDL-C is related to an increased risk for this type of malignancy.
PubMed: 35956117
DOI: 10.3390/jcm11154503 -
Frontiers in Endocrinology 2022Subclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Subclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The aim of the systematic review and meta-analysis was to evaluate whether levothyroxine has a beneficial or harmful effect on older patients with SCH.
METHODS
Databases including PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Weipu and China National Knowledge Infrastructure were searched from inception until December 21, 2021. Subjects must be diagnosed with SCH, and older than or equal to 60 years of age. Interventions should be thyroid hormone therapy (e.g. levothyroxine). The literature was independently screened by 2 researchers. Statistical analysis was performed using RevMan5.3 software.
RESULTS
A total of 13 articles were included. Meta-analysis results showed that in older SCH patients, levothyroxine can significantly reduce cholesterol (TC) ( < 0.00001), triglyceride (TG) ( < 0.00001), low-density lipoprotein cholesterol (LDL-C) ( = 0.03) and apolipoprotein B (ApoB) ( < 0.00001). In addition, levothyroxine had no significant effect on bone mineral density, fatigue, hypothyroidism symptoms, quality of life, BMI, cognitive function, depression, blood pressure, etc. in older SCH patients, and also did not significantly increase the incidence of adverse events.
CONCLUSIONS
Among older SCH patients, levothyroxine treatment may reduce TC, TG, LDL-C, and ApoB.
Topics: Aged; Apolipoproteins B; Cholesterol; Cholesterol, LDL; Humans; Hypothyroidism; Quality of Life; Thyroxine; Triglycerides
PubMed: 35909574
DOI: 10.3389/fendo.2022.913749 -
Biomedicines Jun 2022Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, -glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
PubMed: 35884816
DOI: 10.3390/biomedicines10071511 -
European Journal of Clinical... Nov 2022Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG.
METHODS
Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022.
RESULTS
Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions.
CONCLUSIONS
In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.
Topics: Apolipoprotein B-48; Apolipoprotein C-III; Cholesterol, LDL; Humans; Hyperlipidemias; Hypertriglyceridemia; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 35851450
DOI: 10.1111/eci.13841