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Orphanet Journal of Rare Diseases Feb 2024Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally.
METHODS
In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR.
RESULTS
Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies (I = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05).
CONCLUSIONS
Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.
Topics: Humans; Male; Female; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Mutation; Delayed Diagnosis; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Oxidoreductases Acting on CH-NH Group Donors; Acyl-CoA Dehydrogenase
PubMed: 38365830
DOI: 10.1186/s13023-024-03072-6 -
Health and Quality of Life Outcomes Feb 2024Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically... (Review)
Review
Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.
Topics: Humans; Iron Chelating Agents; Deferasirox; Deferiprone; Deferoxamine; Quality of Life; Pyridones; Benzoates; Triazoles; Thalassemia; Chelation Therapy; Ferritins; Outcome Assessment, Health Care
PubMed: 38302961
DOI: 10.1186/s12955-023-02221-y -
Head & Neck Jul 2024Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs.
METHODS
Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochran's Q test and I test assessed heterogeneity. Funnel plot and Egger's regression test assessed publication bias.
RESULTS
Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations.
CONCLUSION
Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.
Topics: Humans; Succinate Dehydrogenase; Head and Neck Neoplasms; Paraganglioma; Mutation; Female; Male
PubMed: 38273766
DOI: 10.1002/hed.27652 -
International Journal of Molecular... Jan 2024Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question "Are salivary biomarkers reliable for the diagnosis of Alzheimer's Disease?" Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Lactoferrin; MicroRNAs; Biomarkers
PubMed: 38256241
DOI: 10.3390/ijms25021168 -
Molecular Autism Jan 2024Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract.
METHODS
We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279).
RESULTS
There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]).
LIMITATIONS
All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults.
CONCLUSIONS
There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.
Topics: Adolescent; Child; Humans; Autistic Disorder; Biomarkers; Gastrointestinal Tract; Inflammation; Lactoferrin; Leukocyte L1 Antigen Complex
PubMed: 38233886
DOI: 10.1186/s13229-023-00575-0 -
Systematic Reviews Jan 2024Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses.
METHODS
A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115).
RESULTS
Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I = 84%). The overall quality of the evidence was low-moderate.
DISCUSSION
For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.
Topics: Female; Humans; Pregnancy; Iron; Anemia; Blood Transfusion; Hemoglobins; Ferritins; Postpartum Period; Fatigue
PubMed: 38169415
DOI: 10.1186/s13643-023-02400-4 -
Seminars in Arthritis and Rheumatism Feb 2024The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear. Serum ferritin (SF) is a potential candidate and this systematic review and meta-analysis aimed to reveal the clinical significance of SF in IIM-ILD.
METHODS
Eligible English studies were selected from PubMed, Embase, Web of science and Scopus up to 9 June 2023. The SF levels in patients with IIM-ILD were extracted and pooled. Subgroup analysis was performed based on disease types, sensitivity analysis was conducted by excluding one class of literature at a time, and publication bias was assessed by funnel plot and Egger's test.
RESULTS
Pooled analysis of 1,933 patients with IIM from 19 studies showed that SF levels were significantly higher in IIM-ILD group (WMD=263.53ng/mL, 95% CI: 146.44-380.62, p<0.001) than IIM without ILD, subgroup analysis showed that SF levels in DM-ILD (WMD = 397.67ng/mL, 95% CI:142.84-652.50, p = 0.002) and PM/DM-ILD (WMD = 117.68 ng/mL, 95% CI: 86.32-149.04, p < 0.001) were significantly higher compared to those without ILD. SF levels were significantly higher in rapidly progressive interstitial lung disease group (RP-ILD)(WMD = 484.99 ng/mL, 95% CI: 211.12-758.87, p= 0.001) than chronic ILD(C-ILD) group, subgroup analysis showed that SF levels in DM-RP-ILD (WMD= 509.75 ng/mL, 95% CI: 215.34-804.16, p=0.001) were significantly higher than those in DM-C-ILD group. SF levels were significantly higher in death group (WMD= 722.16 ng/mL, 95% CI: 572.32-872.00, p< 0.001) compared to the survival group, subgroup analysis showed that death patients with DM-ILD(WMD= 735.62 ng/mL, 95% CI:574.92-896.32, p<0.001) and PM-ILD (WMD= 632.56 ng/mL, 95% CI:217.92-1047.19, p=0.003) had significantly higher SF levels than survival group respectively.
CONCLUSION
Increased SF levels can serve as a biomarker for predicting the occurrence, progression and death of patients with IIM-ILD, which can provide early warning sign for intervention and prognosis evaluation for IIM-ILD patients.
Topics: Humans; Myositis; Lung Diseases, Interstitial; Biomarkers; Prognosis; Ferritins; Retrospective Studies
PubMed: 38086199
DOI: 10.1016/j.semarthrit.2023.152350 -
The British Journal of Oral &... Jan 2024Currently, there is growing interest in the potential use of lactoferrin (LTF), a member of the transferrin family, for the improvement of tissue healing. In this sense,... (Review)
Review
Currently, there is growing interest in the potential use of lactoferrin (LTF), a member of the transferrin family, for the improvement of tissue healing. In this sense, a literature search was conducted to integrate data published on the effect of LTF on jawbone repair. PubMed/MEDLINE, Scopus, Embase, Web of Science, LILACS, and Cochrane databases were retrieved according to the PRISMA 2020 statement. Articles in English, Spanish, and Portuguese were recovered, with no year restriction. In vitro, in vivo, and clinical studies were selected. A total of 742 articles were retrieved, 11 of which met the inclusion criteria (5 in vitro and 5 in vivo studies, and one clinical trial). The included data demonstrated wide variations in study design and LTF therapy protocols. Cell proliferation and viability were the primary outcomes evaluated in the in vitro studies, all of which reported a potential effect of LTF on the repair process. Of three in vivo studies, one reported a reduction in the overall healing rate, whereas the other two showed that LTF inhibited bone resorption and increased bone formation. The clinical trial's findings showed that LTF is a potential promoter of wound repair in patients with medication-related osteonecrosis of the jaws. Overall, data from the studies support a potential effect of LTF therapy on the process of jawbone repair.
Topics: Humans; Lactoferrin; Osteonecrosis; Jaw
PubMed: 38042716
DOI: 10.1016/j.bjoms.2023.10.019 -
Obesity Surgery Jan 2024This systematic review and meta-analysis study aimed to estimate changes in blood nutrient concentrations and nutrient deficiencies in adolescents following bariatric... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and meta-analysis study aimed to estimate changes in blood nutrient concentrations and nutrient deficiencies in adolescents following bariatric surgery.
METHODS
We searched PubMed, Scopus, and the Web of Science to find studies published between January 2000 and August 2023. Observational studies reporting the mean blood concentration of nutrients before and after bariatric surgery or the proportion of nutrient deficiencies after the surgery in healthy adolescents were selected.
RESULTS
Fifteen studies were included. Gastric bypass and sleeve gastrostomy were the most common types of surgery. Vitamin D, iron, or ferritin, vitamin B12, calcium, and folic acid were the most studied nutrients, respectively. Other nutrients examined in the studies included zinc, phosphorus, and albumin. The serum ferritin increased by 21 mcg/L (95% CI = 10.0, 32.0 mcg/L) after the surgery, but there were no significant alterations in other nutrients. The postoperative prevalence of low albumin, ferritin, vitamin D, and vitamin B12 levels was 10%, 49%, 41%, and 20%, respectively. Also, 23% had an iron deficiency, and 10% had a calcium deficiency after bariatric surgery.
CONCLUSIONS
The serum ferritin level increased following bariatric surgery in adolescents. Vitamin D and ferritin deficiencies were estimated to be present in more than one-third of adolescents after the surgery.
Topics: Humans; Adolescent; Obesity, Morbid; Calcium; Bariatric Surgery; Gastric Bypass; Vitamins; Ferritins; Vitamin D; Vitamin B 12; Albumins
PubMed: 37991712
DOI: 10.1007/s11695-023-06955-y -
The Cochrane Database of Systematic... Nov 2023Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead... (Review)
Review
BACKGROUND
Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018.
OBJECTIVES
To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions.
AUTHORS' CONCLUSIONS
The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.
Topics: Child; Humans; beta-Thalassemia; Calcium Channel Blockers; Iron Overload; Iron; Cardiomyopathies; Amlodipine; Iron Chelating Agents; Ferritins; Edema
PubMed: 37975597
DOI: 10.1002/14651858.CD011626.pub3