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International Urology and Nephrology Sep 2019We aimed to evaluate the prognostic value of serum anti-PLA2R and glomerular PLA2R deposit (gPLA2R) in predicting remission of proteinuria in Primary Membranous... (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to evaluate the prognostic value of serum anti-PLA2R and glomerular PLA2R deposit (gPLA2R) in predicting remission of proteinuria in Primary Membranous Nephropathy (PMN) patients.
METHODS
PUBMED, EMBASE, WEB OF SCIENCE, COCHRANE LIBRARY and CNKI were searched from 2008 January to December 2018. Heterogeneity was assessed by Cochran Q test and I. Source of heterogeneity was explored by subgroup analysis and sensitivity analysis.
RESULTS
Totally 2345 patients from 29 cohort studies were eligible for inclusion. The results suggested that PMN patients with negative anti-PLA2R at the time of biopsy had a 1.31 times (95% CI 1.12-1.46, p < 0.05) higher possibility in achieving remission than those with positive anti-PLA2R. The clearance of anti-PLA2R at the end of immunosuppressive therapy showed an even greater chance of achieving remission (RR = 2.86, 95% CI 1.75-4.69, p < 0.05). The relative ratios for complete remission and spontaneous remission with negative anti-PLA2R were 1.65 (95% CI 1.46-1.87, p < 0.05) and 1.93, respectively (95% CI 1.53-2.45, p < 0.05), and heterogeneity percentages were I = 18% and 46%, respectively. The possibility for remission was significantly greater among PMN patients with negative gPLA2R (RR = 1.30, 95% CI 1.13-1.50, p < 0.05). Subgroup analyses revealed that retrospective design of study might be the potential source of heterogeneity.
CONCLUSIONS
Negative anti-PLA2R or gPLA2R might predict higher possibility of remission, and the presence of anti-PLA2R or gPLA2R might serve as a useful biomarker for clinical outcome and predicting response to immunosuppressive therapy in PMN.
Topics: Autoantibodies; Glomerulonephritis, Membranous; Humans; Prognosis; Proteinuria; Receptors, Phospholipase A2
PubMed: 31140029
DOI: 10.1007/s11255-019-02147-9 -
BMC Musculoskeletal Disorders Apr 2019This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory...
BACKGROUND
This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms?
METHODS
The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool.
RESULTS
In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10).
CONCLUSION
In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.
Topics: Biomarkers; Cross-Sectional Studies; Humans; Inflammation Mediators; Observational Studies as Topic; Prospective Studies; Sciatica
PubMed: 30967132
DOI: 10.1186/s12891-019-2541-0 -
Critical Care (London, England) Feb 2019With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.
METHODS
After searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.
RESULTS
In total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1β, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.
CONCLUSIONS
This meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.
Topics: Antigens, Human Platelet; Biomarkers; Bronchoalveolar Lavage Fluid; Hepatocyte Growth Factor; Humans; Interleukin-8; Lung; Plasminogen Activator Inhibitor 1; Platelet Activating Factor; Receptor for Advanced Glycation End Products; Respiratory Distress Syndrome
PubMed: 30755248
DOI: 10.1186/s13054-019-2336-6 -
Multiple Sclerosis and Related Disorders Jan 2019Phospholipases A2 (PLA) are a diverse group of enzymes that cleave the fatty acids of membrane phospholipids. They play critical roles in pathogenesis of... (Meta-Analysis)
Meta-Analysis
Phospholipases A2 (PLA) are a diverse group of enzymes that cleave the fatty acids of membrane phospholipids. They play critical roles in pathogenesis of neurodegenerative diseases such as multiple sclerosis by enhancing oxidative stress and initiating inflammation. The levels of PLA activity in MS patients compared to controls and role of inhibiting PLA activity on severity scores in different experimental models are not comprehensively assessed in the light of varying evidence from published studies. The objective of this systematic review is to determine the association between PLA activity and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We performed a systematic review of six studies that assessed PLA activity in MS patients compared to controls and nine studies that assessed PLA activity in EAE. sPLA nor Lp-PLA activity were not increased in MS compared to controls in five of those six studies. A difference in sPLA activity was only found in a study that measured the enzyme activity in urine. However, inhibiting cPLA or sPLA led to lower clinical severity or no signs of EAE in mice, and a lower incidence of EAE lesions compared to animals without cPLA inhibition. These findings indicate that PLA appears to play a role in the pathogenesis of EAE.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Humans; Multiple Sclerosis; Phospholipase A2 Inhibitors; Phospholipases A2
PubMed: 30412818
DOI: 10.1016/j.msard.2018.10.115 -
Clinical Biochemistry Sep 2018Platelet-activating factor (PAF) is a glycerylether lipid and one of the most potent endogenous mediators of inflammation. Through its binding to a well-characterized... (Review)
Review
Platelet-activating factor (PAF) is a glycerylether lipid and one of the most potent endogenous mediators of inflammation. Through its binding to a well-characterized receptor it initiates a plethora of cellular pro-inflammatory actions participating by this way to the pathology of most chronic diseases, including cardiovascular and renal diseases, CNS decline and cancer. Among the variety of prudent dietary patterns, Mediterranean Diet (MD) is the dietary pattern with the strongest evidence for its ability to prevent the same chronic diseases. In addition, micronutrients and extracts from several components and characteristic food of the MD can favorably modulate PAF's actions and metabolism either directly or indirectly. However, the role of this traditional diet on PAF metabolism and actions has rarely been studied before. This systematic review summarizes, presents and discusses the outcomes of epidemiologic and intervention studies in humans, investigating the relationships between PAF status and MD. Seventeen full-text articles trying to interlink the components of MD and PAF are found and presented. The results are inconsistent due to the variability of the measured indices and methodology followed. However, preliminary results indicate that the characteristic "healthy" components of the MD, especially, cereals, legumes, vegetables, fish and wine can favorably modulate the pro-inflammatory actions of PAF and regulate its metabolism. Larger, well-controlled studies are necessary to elucidate whether the attenuation of PAF actions can mediate the preventive properties of MD against chronic diseases.
Topics: Cardiovascular Diseases; Chronic Disease; Diet, Mediterranean; Humans; Inflammation Mediators; Platelet Activating Factor
PubMed: 30142319
DOI: 10.1016/j.clinbiochem.2018.08.004 -
Diabetes, Obesity & Metabolism Feb 2019The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to...
The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to examine the contribution of single nucleotide polymorphisms (SNPs) of the ECS to adiposity and glucose metabolism. Database searches identified 734 articles, of which 65 were included; these covered 70 SNPs in genes coding for cannabinoid receptors 1 and 2 (CB , CB ), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). No studies included SNPs relating to monoacylglycerol lipase or diacylglycerol lipase. The CB receptor SNP rs1049353 showed 17 associations with lower body mass index (BMI) and fat mass (five studies). It also showed three associations with lower insulin levels (one study). Conversely, the CB receptor SNP rs806368 was associated with increased BMI and waist circumference (two studies). The FAAH SNP rs324420 was associated with increased obesity (three studies). A haplotype of NAPE-PLD was associated with decreased BMI (one study). A total of 60 SNPs showed no association with any measured outcome. This review suggests a complex but important role of ECS SNPs in energy and glucose metabolism.
Topics: Adiposity; Amidohydrolases; Body Mass Index; Body Weight; Diabetes Mellitus; Endocannabinoids; Gene Frequency; Genetic Association Studies; Humans; Lipid Metabolism; Lipoprotein Lipase; Monoacylglycerol Lipases; Obesity; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Cannabinoid; Signal Transduction
PubMed: 30129173
DOI: 10.1111/dom.13504 -
Inflammation Research : Official... Jan 2019Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia...
BACKGROUND
Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated.
OBJECTIVES
We aim to systematically review and evaluate the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB.
METHODS
We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic to identify cell-culture, animal and human studies reporting the changes in PGs and related lipid mediators of inflammation during the course of LB.
RESULTS
We identified 18 studies to be included into this systematic review. The selected reports consisted of seven cell-culture studies, seven animal studies, and four human studies (from three patient populations). Results from cell-culture and animal studies suggest that PGs and other lipid mediators of inflammation are elevated in LB and may contribute to disease development. The limited number of human studies showed that subjects with Lyme meningitis, Lyme arthritis (LA) and antibiotic-refractory LA had increased levels of an array of PGs and lipid mediators (e.g., LTB 8-isoPGF, and phospholipases A activity). Levels of these markers were significantly reduced following the treatment with antibiotics or non-steroidal anti-inflammatory drugs.
CONCLUSION
Dysregulation of prostaglandins and related lipid mediators may play a role in the etiology of LB and persistence of inflammation that may lead to long-term complications. Further investigation into the precise levels of a wide range of PGs and related factors is critical as it may propose novel markers that can be used for early diagnosis.
Topics: Animals; Biomarkers; Humans; Lyme Disease; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Severity of Illness Index
PubMed: 30121835
DOI: 10.1007/s00011-018-1180-5 -
BMC Infectious Diseases Jun 2018Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (> 80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a subset of infected individuals is incompletely understood, but individual host differences including genetic factors and immune responses have been proposed. We sought to identify genetic risk factors that are associated with more severe disease outcomes for both viruses in order to shed light on possible shared mechanisms of resistance and potential therapeutic interventions.
METHODS
We applied a search strategy using four major databases (Medline, PubMed, Embase, and Global Health) to find all known genetic associations identified to date with dengue or West Nile virus disease. Here we present a review of our findings and a meta-analysis of genetic variants identified.
RESULTS
We found genetic variations that are significantly associated with infections of these viruses. In particular we found variation within the OAS1 (meta-OR = 0.83, 95% CI: 0.69-1.00) and CCR5 (meta-OR = 1.29, 95% CI: 1.08-1.53) genes is significantly associated with West Nile virus disease, while variation within MICB (meta-OR = 2.35, 95% CI: 1.68-3.29), PLCE1 (meta-OR = 0.55, 95% CI: 0.42-0.71), MBL2 (meta-OR = 1.54, 95% CI: 1.02-2.31), and IFN-γ (meta-OR = 2.48, 95% CI: 1.30-4.71), is associated with dengue disease.
CONCLUSIONS
Despite substantial heterogeneity in populations studied, genes examined, and methodology, significant associations with genetic variants were found across studies within both diseases. These gene associations suggest a key role for immune mechanisms in susceptibility to severe disease. Further research is needed to elucidate the role of these genes in disease pathogenesis and may reveal additional genetic factors associated with disease severity.
Topics: 2',5'-Oligoadenylate Synthetase; Dengue; Genetic Predisposition to Disease; Histocompatibility Antigens Class I; Humans; Interferon-gamma; Mannose-Binding Lectin; Phosphoinositide Phospholipase C; Receptors, CCR5; West Nile Fever
PubMed: 29929468
DOI: 10.1186/s12879-018-3186-6 -
Renal Failure Nov 2018THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients.
METHODS
We searched English and Chinese database to 31 December 2017 with the term 'THSD7A' or 'thrombospondin type 1 domain-containing 7A'. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A.
RESULTS
Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%-4%) in all patients and 10% (95% CI, 6%-15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%-4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%-4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%.
CONCLUSIONS
The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended.
Topics: Autoantibodies; Autoantigens; Biopsy; Glomerulonephritis, Membranous; Humans; Incidence; Kidney Glomerulus; Kidney Neoplasms; Prevalence; Receptors, Phospholipase A2; Thrombospondins
PubMed: 29623759
DOI: 10.1080/0886022X.2018.1456457 -
Expert Review of Gastroenterology &... May 2018A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic... (Meta-Analysis)
Meta-Analysis Review
A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic factors and prognosis, but the results were conflicting and inconclusive. Areas covered: In this meta-analysis, the liver function, histopathology, metabolic complications, patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic polymorphism and prognosis were compared between non-obese and obese NAFLD. Pubmed, EMBASE, Cochrane databases were searched to identify eligible studies. The odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models. Expert commentary: This meta-analysis indicated that for NAFLD patients, obesity (according to ethnic-specific BMI cut-off points to define obesity) could predict a worse long-term prognosis. However, obesity may not be an independent factor for the development of NASH or advanced fibrosis in NAFLD patients and NAFLD should be considered as potential population for pharmacologic treatment regardless of obesity. In addition, PNPLA3 rs738409 may be more relevant to the progression of non-obese NAFLD when compared to obese NAFLD. Importantly, large-sample, long-term follow-up cohort studies based on liver biopsy are highly needed due to limited liver pathology and long-term follow-up data at present.
Topics: Adult; Aged; Disease Progression; Genetic Predisposition to Disease; Humans; Lipase; Membrane Proteins; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Odds Ratio; Phenotype; Polymorphism, Genetic; Prognosis; Risk Factors; Severity of Illness Index; Time Factors
PubMed: 29609501
DOI: 10.1080/17474124.2018.1460202