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Thorax Aug 2023Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We aimed to systematically review evidence of soluble markers in peripheral blood or bronchoalveolar lavage fluid (BALF) as biomarkers in SSc-ILD.
METHOD
Five databases were screened for observational or interventional, peer-reviewed studies in adults published between January 2000 and September 2021 that assessed levels of biomarkers in peripheral blood or BALF of SSc-ILD patients compared with healthy controls. Qualitative assessment was performed using Critical Appraisal Skills Programme (CASP) checklists. Standardised mean difference (SMD) in biomarkers were combined in random-effects meta-analyses where multiple independent studies reported quantitative data.
RESULTS
768 published studies were identified; 38 articles were included in the qualitative synthesis. Thirteen studies were included in the meta-analyses representing three biomarkers: KL6, SP-D and IL-8. Greater IL-8 levels were associated with SSc-ILD in both peripheral blood and BALF, overall SMD 0.88 (95% CI 0.61 to 1.15; I=1%). Greater levels of SP-D and KL-6 were both estimated in SSc-ILD peripheral blood compared with healthy controls, at an SMD of 1.78 (95% CI 1.50 to 2.17; I=8%) and 1.66 (95% CI 1.17 to 2.14; I=76%), respectively.
CONCLUSION
We provide robust evidence that KL-6, SP-D and IL-8 have the potential to serve as reliable biomarkers in blood/BALF for supporting the diagnosis of SSc-ILD. However, while several other biomarkers have been proposed, the evidence of their independent value in diagnosis and prognosis is currently lacking and needs further investigation.
PROSPERO REGISTRATION NUMBER
CRD42021282452.
Topics: Adult; Humans; Lung Diseases, Interstitial; Interleukin-8; Pulmonary Surfactant-Associated Protein D; Scleroderma, Systemic; Biomarkers; Lung
PubMed: 36261273
DOI: 10.1136/thorax-2022-219226 -
Molecular Psychiatry May 2024Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by...
Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by alterations in peripheral blood immune cell counts. However, it remains unclear whether these immunological changes are distinct in individuals experiencing suicidal ideation (SI) or suicidal behavior (SB), beyond the context of an MDE. This systematic review and meta-analysis aimed to examine peripheral immune cell profiles across samples with SI/SB and compare them to healthy controls or patients with MDE. A systematic literature search was conducted in MEDLINE, Embase, and PsycINFO for articles published from inception until June 12, 2023. Two independent reviewers screened the articles for inclusion, extracted data, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed using a random-effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for immune cell counts or ratios between groups with and without SI/SB. Heterogeneity across studies was assessed using the restricted maximum-likelihood estimator for tau statistic and I-statistic and tested by the Q test. Publication bias was evaluated using the Egger´s test and funnel plots. Meta-regression analyses were conducted to explore the potential moderating effects of age, gender, current or lifetime SI/SB, and the type of self-harming behavior (SI or SB). The study was registered with PROSPERO (CRD42023433089). The systematic review included 30 studies, with data from 19 studies included in the meta-analyses comprising 139 unique comparisons. Eleven different cell populations or ratios were included, comprising 1973 individuals with SI/SB and 5537 comparison subjects. White blood cell (WBC) and neutrophil counts were higher in individuals with SI/SB than in controls (WBC: SMD = 0.458; 95% CI = 0.367-0.548; p value ≤ 0.001; I = 0.002% and; Neutrophils: SMD = 0.581; 95% CI = 0.408-0.753; p < 0.001), indicating an inflammatory process. The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential marker, demonstrating a notable elevation in individuals with SI/SB (SMD = 0.695; 95% CI = 0.054-1.335; p value = 0.033; I = 94.281%; Q test p value ≤ 0.001). The elevated NLR appears to be primarily driven by the increase in neutrophil counts, as no significant differences were found in lymphocyte counts between groups. Comparisons among participants with and without SI/SB and depression revealed similar trends with increased NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) observed in depressed individuals with SI/SB compared to those without SI/SB. Broad alteration in the peripheral immune cell populations and their ratios were observed in individuals with SI/SB, indicating an immune activation or dysfunction. Notably, these immunological changes were also evident when comparing MDE individuals with and without SI/SB, suggesting that such immune dysfunction associated with suicidality cannot be solely attributed to or explained by depressive symptoms. The NLR, MLR, and PLR ratios, in combination with novel immune cellular and protein biomarkers, open new avenues in understanding the immunological underpinnings of SI/SB. These findings highlight the potential utility of immune markers as part of a multi-modal approach for risk stratification and therapeutic monitoring in SI/SB.
PubMed: 38802507
DOI: 10.1038/s41380-024-02587-5 -
Journal of Neuroimmunology Dec 2023Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic alteration results in the expression of a mutant form of the protein (mHTT) and the formation of intracellular aggregates, inducing an inflammatory state within the affected areas. This dysfunction of inflammatory response leads to elevated levels of related inflammatory markers in both CNS tissue samples and body fluids. This study aims to investigate peripheral/blood concentrations of inflammatory molecules in HD.
METHODS
A search was conducted in MEDLINE, Scopus, Web of Science, and Embase databases until March 30th, 2023. Random-effect meta-analysis was used for exploring concentrations of inflammatory molecules in HD. Subgroup and sensitivity analyses were used to assess heterogeneity among the included studies. The study protocol has been registered in PROSPERO with the ID number CRD42022296078.
RESULTS
Ten studies were included in the meta-analysis. Plasma levels of Interleukin 6 (IL-6) and IL-10 were higher in HD compared to controls. Other biomarkers, namely, complement component C-reactive protein (CRP), C3, interferon-γ (IFN-γ), IL-1, IL-2, IL-8, and tumor necrosis factor-α (TNF-α), did not show any significant differences between the two groups. In addition, the subgroup analysis results established no significant differences in levels of these biomarkers in body fluids among premanifest and manifest HD patients.
CONCLUSION
The results of this study provide evidence for the presence of higher plasma levels of IL-6 and IL-10 in HD patients in comparison with healthy controls.
Topics: Humans; Huntington Disease; Interleukin-6; Interleukin-10; Biomarkers; Tumor Necrosis Factor-alpha; Huntingtin Protein
PubMed: 37984118
DOI: 10.1016/j.jneuroim.2023.578243 -
European Journal of Medical Research Oct 2023Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical activities on the outcomes in HD patients is still unknown. This study explored the effectiveness and safety of all exercise types in HD patients.
METHODS
We searched randomized clinical trials from the PubMed, EMBASE, and Cochrane Library databases. Physical exercises interventions included resistance exercise (RE), aerobic exercise (AE), electrical muscle stimulation (EMS), range of motion (ROM), resistance exercise + aerobic exercise (RE + AE), stretching exercise (STE), respiratory muscle training (RMT), peripheral muscle training (PMT), walking exercise (WE), or usual care/sham exercise (UC/SE). Primary outcomes were six-minute walk test (6-mwt) and quality of life (QOL). Secondary outcomes were Kt/V, VO, hemoglobin (Hb), C-reactive protein (CRP), interleukin-6 (IL-6), and systolic and diastolic blood pressure (sbp and dbp). Frequentist network meta-analysis with multivariate random effects models provided mean with 95% confidence intervals (95%CI).
RESULTS
A total of 58 eligible studies were included. AE, RMT, and RE + AE significantly improved 6-mwt compared with UC/SE. SE was the worst intervention and reduced QOL much more than the UC/SE and other exercise types. AE and RE + AE were associated with higher VO, while ROM and RE + AE induced higher Hb levels. All physical activities did not elevate blood pressure, CRP and IL-6. Only ROM decreased sbp/dbp. CRP is significantly lower in RE.
CONCLUSION
Physical activities play a crucial role in the different outcomes of HD patients. They can be applied to specific area for their specific efficacy.
Topics: Humans; Quality of Life; Network Meta-Analysis; Interleukin-6; Exercise; Prognosis; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 37798739
DOI: 10.1186/s40001-023-01270-9 -
Nutrition, Metabolism, and... Aug 2023The Controlling Nutritional Status (CONUT) score is a tool for assessing the risk of malnutrition (undernutrition) that can be calculated from albumin concentration,... (Meta-Analysis)
Meta-Analysis
AIMS
The Controlling Nutritional Status (CONUT) score is a tool for assessing the risk of malnutrition (undernutrition) that can be calculated from albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration. CONUT score has been proposed as a promising prognostic marker in several clinical settings; however, a consensus on its prognostic value in patients with stroke is lacking. The aim of this systematic review and meta-analysis was to evaluate the relationship between CONUT score and clinical outcomes in patients with stroke based on all current available studies.
DATA SYNTHESIS
Systematic research on PubMed, Scopus and Web of Science from inception to February 2023 was performed on the association between CONUT score and clinical outcomes in patients with stroke. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Methodological quality was evaluated using the Newcastle-Ottawa Scale quality assessment tool. Pooled effect estimation was calculated by a random-effect model. Through the initial literature search, 15 studies (all high-quality) including 16 929 patients were found to be eligible and analysed in the meta-analysis. A significant risk of malnutrition (in most studies defined by a CONUT score ≥5) was directly associated with mortality, higher risk of poor functional outcome according to the modified Rankin Scale and total infection development. Evidence was consistent for acute ischaemic stroke and preliminary for acute haemorrhagic stroke.
CONCLUSION
CONUT score is an independent prognostic indicator, and it is associated with major disability and infection development during hospitalisation.
PROSPERO ID
CRD42022306560.
Topics: Humans; Nutritional Status; Brain Ischemia; Stroke; Malnutrition; Prognosis; Retrospective Studies; Nutrition Assessment
PubMed: 37336716
DOI: 10.1016/j.numecd.2023.05.012 -
Translational Oncology Aug 2023Detection of circulating tumor-derived material (cTM) in the peripheral blood (PB) of cancer patients has been shown to be useful in early diagnosis, prediction of...
BACKGROUND
Detection of circulating tumor-derived material (cTM) in the peripheral blood (PB) of cancer patients has been shown to be useful in early diagnosis, prediction of prognosis, and disease monitoring. However, it has not yet been thoroughly evaluated for pediatric sarcoma patients.
METHODS
We searched the PubMed and EMBASE databases for studies reporting the detection of circulating tumor cells, circulating tumor DNA, and circulating RNA in PB of pediatric sarcoma patients. Data on performance in identifying cTM and its applicability in diagnosis, and evaluation of tumor characteristics, prognostic factors, and treatment response was extracted from publications.
RESULTS
A total of 79 studies were assigned for the present systematic review, including detection of circulating tumor cells (116 patients), circulating tumor DNA (716 patients), and circulating RNA (2887 patients). Circulating tumor cells were detected in 76% of patients. Circulating DNA was detected in 63% by targeted NGS, 66% by shallow WGS, and 79% by digital droplet PCR. Circulating RNA was detected in 37% of patients.
CONCLUSION
Of the cTM from Ewing's sarcoma and rhabdomyosarcoma ctDNA proved to be the best target for clinical application including diagnosis, tumor characterization, prognosis, and monitoring of disease progression and treatment response. For osteosarcoma the most promising targets are copy number alterations or patient specific micro RNAs, however, further investigations are needed to obtain consensus on clinical utility.
PubMed: 37201250
DOI: 10.1016/j.tranon.2023.101690 -
Journal of Clinical Medicine Jul 2023The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a... (Review)
Review
BACKGROUND
The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).
OBJECTIVES
This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.
METHODS
Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).
RESULTS
Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; = 0.04, I = 92%; for heterogeneity < 0.00001) and with higher platelets (8.76 × 10/L, 95% CI 1.62, 15.91; = 0.02, I = 41%; for heterogeneity = 0.06).
CONCLUSIONS
High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.
PubMed: 37445515
DOI: 10.3390/jcm12134480 -
Brain Sciences May 2024Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological... (Review)
Review
Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies.
PubMed: 38790459
DOI: 10.3390/brainsci14050481 -
Academic Emergency Medicine : Official... Apr 2024In patients with acute vestibular syndrome (AVS), differentiating between stroke and nonstroke causes is challenging in the emergency department (ED). Correct diagnosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/INTRODUCTION
In patients with acute vestibular syndrome (AVS), differentiating between stroke and nonstroke causes is challenging in the emergency department (ED). Correct diagnosis of vertigo etiology is essential for early optimum treatment and disposition.
OBJECTIVES
The aim of this systematic review and meta-analysis was to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of peripheral from central causes of AVS.
METHODS
A literature search was conducted for studies published until January 1, 2023, in PubMed, Ovid Medline, and EMBASE databases analyzing biomarkers for the differentiation between central and peripheral AVS. The Quality Assessment of Diagnostic Accuracy Studies questionnaire 2 was used for quality assessment. Pooled standardized mean difference and 95% confidence intervals were calculated if a biomarker was reported in two or more studies. Heterogeneity among included studies was investigated using the I metric.
RESULTS
A total of 17 studies with 859 central and 4844 peripheral causes of acute dizziness or vertigo, and analysis of 61 biomarkers were included. The general laboratory markers creatinine, blood urea nitrogen, albumin, C-reactive protein, glucose, HbA1c, leukocyte counts, and neutrophil counts and the brain-derived biomarkers copeptin, S100 calcium-binding protein β (S100β), and neuron-specific enolase (NSE) significantly differentiated central from peripheral causes of AVS.
CONCLUSIONS
This systematic review and meta-analysis highlights the potential of generalized inflammatory markers and brain-specific blood protein markers of NSE and S100β as diagnostic biomarkers for central from peripheral differentiation in AVS. These results, as a complement to clinical characteristics, provide guidance for future large-scale diagnostic research, in this challenging ED patient population.
Topics: Humans; Vertigo; Vestibular Diseases; Stroke; Biomarkers; Emergency Service, Hospital; Dizziness
PubMed: 38403938
DOI: 10.1111/acem.14864 -
Frontiers in Medicine 2023The effectiveness of N-acetylcysteine (NAC) in treating contrast-induced nephropathy (CIN) has been the subject of conflicting meta-analyses, but the strength of the...
BACKGROUND
The effectiveness of N-acetylcysteine (NAC) in treating contrast-induced nephropathy (CIN) has been the subject of conflicting meta-analyses, but the strength of the evidence for these correlations between NAC use and CIN has not been measured overall.
OBJECTIVE
To evaluate the data from randomized clinical studies (RCTs) that examined the relationships between NAC use and CIN in meta-analyses.
METHODS
Between the creation of the database and April 2023, searches were made in PubMed, Cochrane Library, EMBASE, and Web of Science. N-acetylcysteine, contrast-induced nephropathy, or contrast-induced renal disease were among the search keywords used, along with terms including systematic review and meta-analysis. The Assessment of Multiple Systematic Reviews, version 2, which assigned grades of extremely low, low, moderate, or high quality to each meta-analysis's scientific quality, was used to evaluate each meta-analysis. The confidence of the evidence in meta-analyses of RCTs was evaluated using the Grading of Recommendation, Assessment, Development and Evaluations method, with evidence being rated as very low, low, moderate, or high.
RESULTS
In total, 493 records were screened; of those, 46 full-text articles were assessed for eligibility, and 12 articles were selected for evidence synthesis as a result of the screening process. Based on the pooled data, which was graded as moderate-quality evidence, it can be concluded that NAC can decrease CIN (OR 0.72, 95% CI 0.65-0.79, < 0.00001) and blood levels of serum creatinine (MD -0.09, 95% CI -0.17 to -0.01, = 0.03). In spite of this, there were no associations between NAC and dialysis requirement or mortality in these studies.
CONCLUSION
The results of this umbrella review supported that the renal results were enhanced by NAC. The association was supported by moderate-quality evidence.
SYSTEMATIC REVIEW REGISTRATION
[https://clinicaltrials.gov/], identifier [CRD42022367811].
PubMed: 37790125
DOI: 10.3389/fmed.2023.1235023