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Infection, Genetics and Evolution :... Sep 2021The Severe acute respiratory syndrome may be caused by coronavirus disease which has resulted in a global pandemic. Polymorphisms in the population play a role in...
The Severe acute respiratory syndrome may be caused by coronavirus disease which has resulted in a global pandemic. Polymorphisms in the population play a role in susceptibility to severity. We aimed to perform a systematic review related to the effect of single nucleotide polymorphisms in the development of severe acute respiratory syndrome (SARS). Twenty-eight eligible articles published were identified in PubMed, ScienceDirect, Web of Science, PMC Central and Portal BVS and additional records, with 20 studies performed in China. Information on study characteristics, genetic polymorphisms, and comorbidities was extracted. Study quality was assessed by the STrengthening the REporting of Genetic Association (STREGA) guideline. Few studies investigated the presence of polymorphisms in HLA, ACE1, OAS-1, MxA, PKR, MBL, E-CR1, FcγRIIA, MBL2, L-SIGN (CLEC4M), IFNG, CD14, ICAM3, RANTES, IL-12 RB1, TNFA, CXCL10/IP-10, CD209 (DC-SIGN), AHSG, CYP4F3 and CCL2 with the susceptibility or protection to SARS-Cov. This review provides comprehensive evidence of the association between genetic polymorphisms and susceptibility or protection to severity SARS-CoV. The literature about coronavirus infection, susceptibility to severe acute respiratory syndrome (SARS) and genetic variations is scarce. Further studies are necessary to provide more concrete evidence, mainly related to Covid-19.
Topics: COVID-19; Chemokines; Cytokines; Female; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; HLA Antigens; Humans; Male; Mannose-Binding Lectin; Polymorphism, Genetic
PubMed: 33933633
DOI: 10.1016/j.meegid.2021.104846 -
Pharmacological Reviews Apr 2021The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the...
The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. SIGNIFICANCE STATEMENT: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
Topics: COVID-19; Collectins; Complement Activating Enzymes; Complement C3; Complement Inactivating Agents; Complement System Proteins; Genetic Therapy; Humans; Inflammation Mediators; Lectins; Mannose-Binding Protein-Associated Serine Proteases; Pandemics; Rare Diseases; SARS-CoV-2; Synapses; Ficolins
PubMed: 33687995
DOI: 10.1124/pharmrev.120.000072 -
Journal of Vascular Surgery Jun 2021Restenosis after carotid endarterectomy (CEA) limits its long-term efficacy for stroke prevention. Thus, it is of utmost importance to identify the factors that...
OBJECTIVE
Restenosis after carotid endarterectomy (CEA) limits its long-term efficacy for stroke prevention. Thus, it is of utmost importance to identify the factors that predispose a patient to restenosis after CEA. This systemic review aims to survey the current literature regarding restenosis after CEA and discuss the predictive value of carotid plaque features.
METHODS
A systemic review of studies on the predictive value of carotid plaque features for restenosis after CEA was conducted according to the PRISMA guidelines. PubMed/MEDLINE and Embase databases were searched up to March 20, 2020. Two authors independently extracted the data and assessed the risk of bias with the Quality in Prognosis Studies tool. Given the heterogeneity in the measurement of prognostic factors, types of CEA, and clinical outcomes, a qualitative synthesis was performed.
RESULTS
Twenty-one articles with a sample size that ranged from 11 to 1203 were included in this systematic review. Based on the presence of calcification in original carotid plaques, two progression patterns of restenosis were hypothesized: patients with calcified plaques may experience a temporary increase in the intima-media thickness (IMT) followed by a decrease in IMT after CEA, whereas patients with noncalcified plaques may experience a gradual increase in IMT after CEA. Accordingly, patients with a high calcium score may have a high restenosis rate within 6 months after CEA and a low restenosis rate thereafter. Thus, the late restenosis rate in patients with uniformly echogenic plaques was lower than that in patients with uniformly echolucent plaques. Pathologically, a lipid-rich, inflammatory carotid plaque is associated with a decreased risk of restenosis within 1 year after CEA, mainly owing to the relatively mild reactive intimal hyperplasia at the surgical site and active inflammation in the remaining media and adventitia. Molecular predictors for restenosis included a Mannose-binding lectin 2 genotype, preoperative C-reactive protein, serum homocysteine, apolipoprotein J, vitamin C, and telomere length of carotid plaques.
CONCLUSIONS
This review demonstrated that carotid plaque features, including imaging features, cellular composition, and molecular features, are correlated with the risk of restenosis after CEA. A comprehensive evaluation of plaque characteristics may help to stratify the risk of restenosis after CEA.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Carotid Stenosis; Endarterectomy, Carotid; Female; Humans; Male; Middle Aged; Neointima; Plaque, Atherosclerotic; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Calcification
PubMed: 33253876
DOI: 10.1016/j.jvs.2020.10.084 -
American Journal of Obstetrics and... Aug 2020We performed a systematic review and meta-analysis to determine whether D-mannose reduces urinary tract infection recurrence (ie, cumulative incidence) in adult women... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
We performed a systematic review and meta-analysis to determine whether D-mannose reduces urinary tract infection recurrence (ie, cumulative incidence) in adult women with recurrent urinary tract infection compared with other prevention agents. Secondary outcomes included side effects and compliance with D-mannose use.
DATA SOURCES
Ovid Medline 1946-, Embase 1947-, Scopus 1823-, Cochrane Library, Web of Science 1900-, and ClinicalTrials.gov were searched through 4/15/2020.
STUDY ELIGIBILITY CRITERIA
Systematic review inclusion: randomized controlled trials, prospective cohorts, and retrospective cohorts written in English of women ≥18 years old with recurrent urinary tract infection in which D-mannose was utilized as an outpatient prevention regimen. Systematic review exclusion: lab or animal-based research, study protocols only, and conference abstracts. Meta-analysis inclusion: stated D-mannose dose, follow-up time ≥6 months, a comparison arm to D-mannose, and data available from women ≥18 years of age.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two independent reviewers made abstract, full text, and data extraction decisions. Study methodologic quality was assessed using the Cochrane Risk of Bias tool. Relative risks, confidence intervals, and heterogeneity were computed.
RESULTS
Searches identified 776 unique citations. Eight publications met eligibility: 2 using D-mannose only; 6 using D-mannose combined with another treatment. Seven studies were prospective: 2 randomized controlled trials, 1 randomized cross-over trial, and 4 prospective cohort studies. One retrospective cohort study was included. Three studies met meta-analysis eligibility (1 randomized controlled trial, 1 randomized cross-over trial, and 1 prospective cohort). Pooled relative risk of urinary tract infection recurrence comparing D-mannose to placebo was 0.23 (95% confidence interval, 0.14-0.37; heterogeneity=0%; D-mannose n=125, placebo n=123). Pooled relative risk of urinary tract infection recurrence comparing D-mannose to preventative antibiotics was 0.39 (95% confidence interval, 0.12-1.25; heterogeneity=88%; D-mannose n=163, antibiotics n=163). Adverse side effects were reported in 2 studies assessing D-mannose only (1 study (n=10) reported none; the other reported a low incidence (8/103 participants) of diarrhea). Two studies reported compliance, which was high.
CONCLUSION
D-mannose appears protective for recurrent urinary tract infection (vs placebo) with possibly similar effectiveness as antibiotics. Overall, D-mannose appears well tolerated with minimal side effects-only a small percentage experiencing diarrhea. Meta-analysis interpretation must consider the small number of studies with varied study design and quality and the overall small sample size.
Topics: Adult; Anti-Bacterial Agents; Chemoprevention; Diarrhea; Female; Humans; Mannose; Medication Adherence; Recurrence; Urinary Tract Infections
PubMed: 32497610
DOI: 10.1016/j.ajog.2020.05.048 -
BMC Medical Genomics Sep 2019Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD).
METHODS
We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis.
RESULTS
We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms.
CONCLUSIONS
Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.
Topics: Disease Susceptibility; Humans; Lipopolysaccharide Receptors; Mannose-Binding Lectin; Odds Ratio; Phenotype; Pneumococcal Infections; Polymorphism, Genetic; RNA, Long Noncoding; Risk Factors
PubMed: 31519222
DOI: 10.1186/s12920-019-0572-x -
Archives of Gynecology and Obstetrics Oct 2019Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in...
PURPOSE
Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in primary care units and 30-40% of those treated in hospitals. The risk of UTI in the female population is considered to be 14 times higher than in the male population. The prevalence of bacterial etiology results in a large consumption of broad-spectrum antibiotics, which in turn leads to increased rates of resistant uropathogens. Therefore, non-antibiotic prevention and treatment options are now of great importance.
METHODS
A systematic literature search was performed for the last 20 years (1999-2019) and the efficiencies of these eight different non-antibiotic interventions were analysed and discussed.
RESULTS
This article provides an overview on non-antibiotic options for management of UTI, including the application of cranberry products, the phytodrug Canephron N, probiotics, nonsteroidal anti-inflammatory drugs (NSAID), D-mannose, estrogens, vitamins, and immunotherapy.
CONCLUSIONS
The last 20 years of research on non-antibiotic approaches in UTI have not brought conclusive evidence that antibiotic usage can be replaced completely by non-antibiotic options. Hence, antibiotics still remain a gold standard for UTI treatment and prevention. However, changing the therapeutic strategy by including non-antibiotic measures in the management of UTI could be successful in avoiding antimicrobial resistance at least to some extent.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Humans; Male; Urinary Tract Infections
PubMed: 31350663
DOI: 10.1007/s00404-019-05256-z -
Cancer Management and Research 2019Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools... (Review)
Review
INTRODUCTION
Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools are fine-needle aspiration (FNA) and histological examination following thyroidectomy. The metabolite profile alterations of thyroid cells (oncometabolites) can be considered for current TC diagnosis and management protocols.
METHODS
This systematic review focuses on metabolite alterations within the plasma, FNA specimens, and tissue of malignant TC contrary to benign, goiter, or healthy TC samples. A systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted, and the final 31 studies investigating metabolite biomarkers of TC were included.
RESULTS
A total of 15 targeted studies and 16 untargeted studies revealed several potential metabolite signatures of TC such as glucose, fructose, galactose, mannose, 2-keto-d-gluconic acid and rhamnose, malonic acid and inosine, cholesterol and arachidonic acid, glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, cell membrane phospholipids, estrogen metabolites such as 16 alpha-OH E1/2-OH E1 and catechol estrogens (2-OH E1), and purine and pyrimidine metabolites, which were suggested as the TC oncometabolite.
CONCLUSION
Citrate was suggested as the first most significant biomarker and lactate as the second one. Further research is needed to confirm these biomarkers as the TC diagnostic oncometabolite.
PubMed: 30881111
DOI: 10.2147/CMAR.S188661 -
American Journal of Transplantation :... Apr 2019Mannose-binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have... (Meta-Analysis)
Meta-Analysis
Mannose-binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have been associated with susceptibility to infection, although data in solid organ transplant recipients remains inconclusive. This meta-analysis was primarily aimed at investigating the association between posttransplant bacterial and fungal infection and variant alleles of MBL2 gene SNPs in the promoter/5' untranslated region and exon 1. Cytomegalovirus (CMV) infection and/or disease were considered secondary outcomes. PubMed, EMBASE, and Web of Knowledge were searched for relevant articles up to August 2018. Eleven studies (comprising 1858 patients) were included, with liver transplant (LT) recipients accounting for 80.4% of the pooled population. As compared to high-MBL expression haplotypes (YA/YA, YA/XA), any MBL-deficient haplotype was associated with an increased risk of posttransplant bacterial and fungal infections (risk ratio [RR]: 1.30; P = .04). Low/null-MBL expression haplotypes (XA/O, O/O) also increased the risk of primary outcome (RR: 1.51; P = .008) and CMV events (RR: 1.50; P = .006). No effect was observed for individual promoter SNPs. In conclusion, MBL-deficient haplotypes are associated with a significant, albeit moderate, increase in the risk of posttransplant infection, with this association being mainly restricted to LT recipients.
Topics: Humans; Infections; Mannose-Binding Lectin; Organ Transplantation; Polymorphism, Genetic; Risk Factors
PubMed: 30378749
DOI: 10.1111/ajt.15160 -
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 -
PloS One 2018Chronic Obstructive Pulmonary Disease (COPD) impacts differently on patients at similar grades, suggesting that factors other than lung function may influence patients'...
BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) impacts differently on patients at similar grades, suggesting that factors other than lung function may influence patients' experience of the disease. Recent studies have found associations between genetic variations and patient-reported outcomes (PROs). Identifying these associations might be fundamental to predict the disease progression and develop tailored interventions. This systematic review aimed to identify the genetic variations associated with PROs in COPD.
METHODS AND FINDINGS
Databases were searched until July 2017 (PROSPERO: CRD42016041639) and additional searches were conducted scanning the reference list of the articles. Two independent reviewers assessed the quality of studies using the Q-Genie checklist. This instrument is composed of 11 questions, each subdivided in 7 options from 1 poor-7 excellent. Thirteen studies reporting 5 PROs in association with genes were reviewed. Studies were rated between "good quality" (n = 8) and "moderate" (n = 5). The most reported PRO was frequency of exacerbations (n = 7/13), which was mainly associated with MBL2 gene variants. Other PRO's were health-related quality of life (HRQOL) (n = 4/13), depressive symptoms (n = 1/13), exacerbation severity (n = 1/13) and breathlessness, cough and sputum (n = 1/13), which were commonly associated with other genetic variants.
CONCLUSIONS
Although a limited number of PRO's have been related to genetic variations, findings suggest that there is a significant association between specific gene variants and the number/severity of exacerbations, depressive symptoms and HRQOL. Further research is needed to confirm these findings and assess the genetic influence on other dimensions of patients' lives, since it may enhance our understanding and management of COPD.
Topics: Disease Progression; Genetic Predisposition to Disease; Genetic Profile; Genetic Variation; Humans; Mannose-Binding Lectin; Patient Reported Outcome Measures; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 29927965
DOI: 10.1371/journal.pone.0198920