-
Scandinavian Journal of Immunology May 2021Complex interactions between the environment and the mucosal immune system underlie inflammatory bowel disease (IBD). The involved cytokine signalling pathways are...
BACKGROUND
Complex interactions between the environment and the mucosal immune system underlie inflammatory bowel disease (IBD). The involved cytokine signalling pathways are modulated by a number of transcription factors, one of which is runt-related transcription factor 3 (RUNX3).
OBJECTIVE
To systematically review the immune roles of RUNX3 in immune regulation, with a focus on the context of IBD.
METHODS
Relevant articles and reviews were identified through a Scopus search in April 2020. Information was categorized by immune cell types, analysed and synthesized. IBD transcriptome data sets and FANTOM5 regulatory networks were processed in order to complement the literature review.
RESULTS
The available evidence on the immune roles of RUNX3 allowed for its description in twelve cell types: intraepithelial lymphocyte, Th1, Th2, Th17, Treg, double-positive T, cytotoxic T, B, dendritic, innate lymphoid, natural killer and macrophages. In the gut, the activity of RUNX3 is multifaceted and context-dependent: it may promote homeostasis or exacerbated reactions via cytokine signalling and regulation of receptor expression. RUNX3 is mostly engaged in pathways involving ThPOK, T-bet, IFN-γ, TGF-β/IL-2Rβ, GATA/CBF-β, SMAD/p300 and a number of miRNAs. RUNX3 targets relevant to IBD may include RAG1, OSM and IL-17B. Moreover, in IBD RUNX3 expression correlates positively with GZMM, and negatively with IFNAR1, whereas in controls, it strongly associates with TGFBR3.
CONCLUSIONS
Dysregulation of RUNX3, mostly in the form of deficiency, likely contributes to IBD pathogenesis. More clinical research is needed to examine RUNX3 in IBD.
Topics: B-Lymphocytes; Core Binding Factor Alpha 3 Subunit; Dendritic Cells; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Intraepithelial Lymphocytes; T-Lymphocytes
PubMed: 33528856
DOI: 10.1111/sji.13025 -
Nutrients Jan 2021Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs)....
Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are , respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms "vitamin D" and "" or "Respiratory Syncytial Virus" or "Influenza". A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Topics: Child; Child, Preschool; Cytokines; Humans; Immunity, Innate; Immunomodulation; Infant; Influenza A virus; Influenza, Human; Pneumonia, Pneumococcal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Vitamin D
PubMed: 33478006
DOI: 10.3390/nu13010276 -
The Cochrane Database of Systematic... Jan 2021Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations.
OBJECTIVES
To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, 21 other databases and two trials registers up to 21 July 2020, together with contacting key organisations to identify additional studies.
SELECTION CRITERIA
We included cluster- or individually-randomised controlled trials (RCTs) carried out among the general population from any country, aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. We included trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risks of bias. We followed Cochrane methods in this review.
MAIN RESULTS
Our search identified 3538 records, after removing duplicates. We included 10 trials, involving 3319 participants, carried out in Bangladesh, Brazil, India, Kuwait, Philippines, South Africa and Sri Lanka. We identified two ongoing studies and one study is awaiting classification. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, three trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial used various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added may reduce by 27% the risk of anaemia in populations (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.55 to 0.97; 5 studies, 2315 participants; low-certainty evidence). It is uncertain whether iron-fortified wheat flour with or without other micronutrients reduces iron deficiency (RR 0.46, 95% CI 0.20 to 1.04; 3 studies, 748 participants; very low-certainty evidence) or increases haemoglobin concentrations (in g/L) (mean difference MD 2.75, 95% CI 0.71 to 4.80; 8 studies, 2831 participants; very low-certainty evidence). No trials reported data on adverse effects in children (including constipation, nausea, vomiting, heartburn or diarrhoea), except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to the risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (mean difference (MD) 0.04, 95% CI -0.02 to 0.11; 2 studies, 558 participants; moderate-certainty evidence). Iron-fortified wheat flour with other micronutrients added versus unfortified wheat flour (nil micronutrients added) It is unclear whether wheat flour fortified with iron, in combination with other micronutrients decreases anaemia (RR 0.77, 95% CI 0.41 to 1.46; 2 studies, 317 participants; very low-certainty evidence). The intervention probably reduces the risk of iron deficiency (RR 0.73, 95% CI 0.54 to 0.99; 3 studies, 382 participants; moderate-certainty evidence) and it is unclear whether it increases average haemoglobin concentrations (MD 2.53, 95% CI -0.39 to 5.45; 4 studies, 532 participants; very low-certainty evidence). No trials reported data on adverse effects in children. Nine out of 10 trials reported sources of funding, with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials.
AUTHORS' CONCLUSIONS
Fortification of wheat flour with iron (in comparison to unfortified flour, or where both groups received the same other micronutrients) may reduce anaemia in the general population above two years of age, but its effects on other outcomes are uncertain. Iron-fortified wheat flour in combination with other micronutrients, in comparison with unfortified flour, probably reduces iron deficiency, but its effects on other outcomes are uncertain. None of the included trials reported data on adverse side effects except for risk of infection or inflammation at the individual level. The effects of this intervention on other health outcomes are unclear. Future studies at low risk of bias should aim to measure all important outcomes, and to further investigate which variants of fortification, including the role of other micronutrients as well as types of iron fortification, are more effective, and for whom.
Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Edetic Acid; Female; Ferric Compounds; Ferrous Compounds; Flour; Food, Fortified; Fumarates; Hemoglobin A; Humans; Infant; Iron; Iron Deficiencies; Male; Micronutrients; Middle Aged; Randomized Controlled Trials as Topic; Triticum; Young Adult
PubMed: 33461239
DOI: 10.1002/14651858.CD011302.pub3 -
British Journal of Clinical Pharmacology May 2021Hypophosphataemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to... (Meta-Analysis)
Meta-Analysis Review
AIMS
Hypophosphataemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. The aim of this study was to determine frequency, severity, duration and risk factors of incident hypophosphataemia after treatment with FCM and IIM.
METHODS
A systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005-2020 was carried out using the search terms 'ferric carboxymaltose' OR 'iron isomaltoside'. Prospective clinical trials reporting outcomes on hypophosphataemia rate, mean nadir serum phosphate and/or change in mean serum phosphate from baseline were selected. Hypophosphataemia rate and severity were compared for studies on IIM vs. FCM after stratification for chronic kidney disease. Meta-regression analysis was used to investigate risk factors for hypophosphataemia.
RESULTS
Across the 42 clinical trials included in the meta-analysis, FCM induced a significantly higher incidence of hypophosphataemia than IIM (47%, 95% CI 36-58% vs. 4%, 95% CI 2-5%), and significantly greater mean decreases in serum phosphate (0.40 vs. 0.06 mmol/L). Hypophosphataemia persisted at the end of the study periods (maximum 3 months) in up to 45% of patients treated with FCM. Meta-regression analysis identified low baseline serum ferritin and transferrin saturation, and normal kidney function as significant predictors of hypophosphataemia.
CONCLUSION
FCM is associated with a high risk of hypophosphataemia, which does not resolve for at least 3 months in a large proportion of affected patients. More severe iron deficiency and normal kidney function are risk factors for hypophosphataemia.
Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Fibroblast Growth Factor-23; Humans; Hypophosphatemia; Maltose; Prospective Studies
PubMed: 33188534
DOI: 10.1111/bcp.14643 -
Cancers Oct 2020Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disorder, first reported in 1926, caused by a deficiency of ATM (Ataxia-Telangiectasia Mutated) protein. The... (Review)
Review
Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disorder, first reported in 1926, caused by a deficiency of ATM (Ataxia-Telangiectasia Mutated) protein. The disease is characterized by progressive cerebellar neurodegeneration, immunodeficiency, leukemia, and lymphoma cancer predisposition. Immunoglobulin replacement, antioxidants, neuroprotective factors, growth, and anti-inflammatory hormones are commonly used for A-T treatment, but, to date, there is no known cure. Bone marrow transplantation (BMT) is a successful therapy for several forms of diseases and it is a valid approach for tumors, hemoglobinopathies, autoimmune diseases, inherited disorders of metabolism, and other pathologies. Some case reports of A-T patients have shown that BMT is becoming a good option, as a correct engraftment of healthy cells can restore some aspects of immunologic capacity. However, due to a high risk of mortality as a result of a clinical and cellular hypersensitivity to ionizing radiation and radiomimetic drugs, a specific non-myeloablative conditioning is required before BMT. Although BMT might be considered as one promising therapy for the treatment of immunological defects and cancer prevention in selected A-T patients, the therapy is currently not recommended or recognized and the eligibility of A-T patients for BMT is a point to deepen and deliberate.
PubMed: 33142696
DOI: 10.3390/cancers12113207 -
Advances in Nutrition (Bethesda, Md.) Jun 2021Vitamin A (VA) is an essential nutrient often lacking in the diets of people in developing countries. Accurate biomarkers of VA status are vital to inform public health... (Meta-Analysis)
Meta-Analysis
Vitamin A (VA) is an essential nutrient often lacking in the diets of people in developing countries. Accurate biomarkers of VA status are vital to inform public health policy and monitor interventions. The relative dose-response (RDR) and modified-RDR (MRDR) tests are semi-quantitative screening tests for VA deficiency that have been used in Demographic and Health Surveys and VA intervention studies. A systematic review and meta-analysis of sensitivity and specificity were conducted to summarize the physiological evidence to support the RDR tests as methods to assess VA status and investigate the impact of different pathological and physiological states on the tests. A total of 190 studies were screened for inclusion, with 21 studies comparing the RDR tests with the gold-standard biomarker, liver VA concentration (68% and 80% sensitivity and 85% and 69% specificity for the RDR and MRDR, respectively). Nearly all studies with VA interventions in VA-deficient populations demonstrated a response of the tests to VA intake that would be expected to improve VA status. The impacts of chronic liver disease, protein malnutrition, age, pregnancy and lactation, infection and inflammation, and various other conditions were examined in 51 studies. The RDR and MRDR tests were reported to have been used in 39 observational studies, and the MRDR has been used in at least 6 national micronutrient surveys. The RDR and MRDR are sensitive tests for determining population VA status and assessing VA interventions. Although they are robust to most physiological and pathological states, caution may be warranted when using the tests in neonates, individuals with chronic liver disease, and those with protein or iron malnutrition. Research on further improvements to the tests to increase accessibility, such as sampling breast milk instead of blood or using intramuscular doses in subjects with malabsorption, will allow wider adoption. This review was registered with PROSPERO as CRD42019124180.
Topics: Breast Feeding; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Lactation; Milk, Human; Nutritional Status; Vitamin A; Vitamin A Deficiency
PubMed: 33130884
DOI: 10.1093/advances/nmaa136 -
Open Heart Oct 2020We conducted a systematic review and meta-analysis of studies that compared levels of molecular biomarkers in women with peripartum cardiomyopathy (PPCM) to those in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis of studies that compared levels of molecular biomarkers in women with peripartum cardiomyopathy (PPCM) to those in healthy pregnant and postpartum women to: (1) assess the evidence for prolactin (PRL) metabolism in PPCM, (2) ascertain the evidence for biomarkers of iron deficiency in PPCM, (3) identify other biomarkers associated with PPCM.
METHODS
We searched Medline, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL) and the Global Health Library from inception without language restriction for studies that compared biomarkers levels in PPCM cases to healthy controls. Pooled standardised mean difference (SMD) was generated using a random effects model for the difference in levels of biomarkers.
RESULTS
Two studies assessed the association of PRL with PPCM, and reported that PPCM cases have higher levels of total PRL. No studies investigated iron metabolism in PPCM. Other biomarkers associated with PPCM included serum levels of natriuretic peptides (SMD=3.77, 95% CI 0.71 to 6.82), albumin (SMD=-0.67, 95% CI -1.01 to -0.32), C-reactive protein (SMD=1.67, 95% CI 0.22 to 3.12), selenium (SMD=-0.73, 95% CI -1.58 to 0.12), cardiac troponins (SMD=1.06, 95% CI 0.33 to 1.80), creatinine (SMD=0.51, 95% CI 0.33 to 0.69), white bloodcells (SMD=0.44, 95 % CI 0.07 to 0.82), haemoglobin (SMD=-0.45, 95% CI -0.64 to-0.26).
CONCLUSIONS
More robust molecular studies are needed to explore the association between prolactin and PPCM in human subjects and to determine the extent to which iron deficiency (with or without anaemia) contributes to the risk of PPCM.
Topics: Anemia, Iron-Deficiency; Biomarkers; Cardiomyopathies; Female; Heart Disease Risk Factors; Humans; Iron; Iron Deficiencies; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Prolactin; Risk Assessment
PubMed: 33060142
DOI: 10.1136/openhrt-2020-001430 -
Orphanet Journal of Rare Diseases Oct 2020N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia... (Review)
Review
BACKGROUND
N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management.
METHODS
Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers.
RESULTS
In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported.
CONCLUSIONS
Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.
Topics: Amino-Acid N-Acetyltransferase; Ammonia; Humans; Hyperammonemia; Infant, Newborn; Urea Cycle Disorders, Inborn
PubMed: 33036647
DOI: 10.1186/s13023-020-01560-z -
Nutrients Sep 2020Nutritional assessment is essential to identify patients with acute kidney injury (AKI) who are protein-energy wasting (PEW) and at risk of poor clinical outcomes. This... (Meta-Analysis)
Meta-Analysis
Nutritional assessment is essential to identify patients with acute kidney injury (AKI) who are protein-energy wasting (PEW) and at risk of poor clinical outcomes. This systematic review aimed to investigate the relationship of nutritional assessments for PEW with clinical outcomes in patients with AKI. A systematic search was performed in PubMed, Scopus, and Cochrane Library databases using search terms related to PEW, nutrition assessment, and AKI to identify prospective cohort studies that involved AKI adult patients with at least one nutritional assessment performed and reported relevant clinical outcomes, such as mortality, length of stay, and renal outcomes associated with the nutritional parameters. Seventeen studies reporting eight nutritional parameters for PEW assessment were identified and mortality was the main clinical outcome reported. A meta-analysis showed that PEW assessed using subjective global assessment (SGA) was associated with greater mortality risk (RR: 1.99, 95% CI: 1.36-2.91). Individual nutrition parameters, such as serum chemistry, body mass, muscle mass, and dietary intakes, were not consistently associated with mortality. In conclusion, SGA is a valid tool for PEW assessment in patients with AKI, while other nutrition parameters in isolation had limited validity for PEW assessment.
Topics: Acute Kidney Injury; Aged; Female; Humans; Kidney; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Protein-Energy Malnutrition; Treatment Outcome
PubMed: 32933198
DOI: 10.3390/nu12092809 -
Virus Research Nov 2020Susceptibility to severe viral infections was reported to be associated with genetic variants in immune response genes using case reports and GWAS studies. SARS-CoV-2 is...
BACKGROUND
Susceptibility to severe viral infections was reported to be associated with genetic variants in immune response genes using case reports and GWAS studies. SARS-CoV-2 is an emergent viral disease that caused millions of COVID-19 cases all over the world. Around 15 % of cases are severe and some of them are accompanied by dysregulated immune system and cytokine storm. There is increasing evidence that severe manifestations of COVID-19 might be attributed to human genetic variants in genes related to immune deficiency and or inflammasome activation (cytokine storm).
OBJECTIVE
Identify the candidate genes that are likely to aid in explaining severe COVID-19 and provide insights to understand the pathogenesis of severe COVID-19.
METHODS
In this article, we systematically reviewed genes related to viral susceptibility that were reported in human genetic studies (Case-reports and GWAS) to understand the role of host viral interactions and to provide insights into the pathogenesis of severe COVID-19.
RESULTS
We found 40 genes associated with viral susceptibility and 21 of them were associated with severe SARS-CoV disease and severe COVID-19. Some of those genes were implicated in TLR pathways, others in C-lectin pathways, and others were related to inflammasome activation (cytokine storm).
CONCLUSION
This compilation represents a list of candidate genes that are likely to aid in explaining severe COVID-19 which are worthy of inclusion in gene panels and during meta-analysis of different variants in host genetics studies of COVID-19. In addition, we provide several hypotheses for severe COVID-19 and possible therapeutic targets.
Topics: Adolescent; Adult; Age Factors; Alleles; Betacoronavirus; COVID-19; Coronavirus Infections; Genetic Predisposition to Disease; Genome-Wide Association Study; Host-Pathogen Interactions; Humans; Inflammasomes; Lectins; Middle Aged; Models, Genetic; Molecular Targeted Therapy; Mutation; Pandemics; Pneumonia, Viral; Polymorphism, Single Nucleotide; SARS-CoV-2; Severe Acute Respiratory Syndrome; Signal Transduction; Toll-Like Receptor 3; Toll-Like Receptors; Virus Diseases; Young Adult; COVID-19 Drug Treatment
PubMed: 32918943
DOI: 10.1016/j.virusres.2020.198163