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The Cochrane Database of Systematic... Feb 2023Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains... (Review)
Review
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
OBJECTIVES
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS
We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS
Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Topics: Male; Female; Humans; Thalassemia; Gingivitis
PubMed: 36732291
DOI: 10.1002/14651858.CD012969.pub3 -
Human Genetics Dec 2021ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to...
ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. Less common are heart defects, eye anomalies, renal abnormalities, and gastrointestinal dysfunction. ATR-X syndrome is caused by germline variants in the ATRX gene. Until recently, the diagnosis of the ATR-X syndrome had been guided by the classical clinical manifestations and confirmed by molecular techniques. However, our new systematic analysis shows that the only clinical sign shared by all affected individuals is intellectual disability, with the other manifestations varying even within the same family. More than 190 different germline ATRX mutations in some 200 patients have been analyzed. With improved and more frequent analysis by molecular technologies, more subtle deletions and insertions have been detected recently. Moreover, emerging technologies reveal non-classic phenotypes of ATR-X syndrome as well as the description of a new clinical feature, the development of osteosarcoma which suggests an increased cancer risk in ATR-X syndrome. This review will focus on the different types of inherited ATRX mutations and their relation to clinical features in the ATR-X syndrome. We will provide an update of the frequency of clinical manifestations, the affected organs, and the genotype-phenotype correlations. Finally, we propose a shift in the diagnosis of ATR-X patients, from a clinical diagnosis to a molecular-based approach. This may assist clinicians in patient management, risk assessment and genetic counseling.
Topics: Animals; Humans; Intellectual Disability; Mental Retardation, X-Linked; Molecular Diagnostic Techniques; Mutation; alpha-Thalassemia
PubMed: 34524523
DOI: 10.1007/s00439-021-02361-5 -
Hematology (Amsterdam, Netherlands) Dec 2019Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various...
OBJECTIVES
Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease.
METHODS
A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease.
RESULTS
Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators.
DISCUSSION AND CONCLUSION
Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.
Topics: Female; Humans; Hypoxia; Iron Overload; Kidney Diseases; Male; beta-Thalassemia
PubMed: 30947625
DOI: 10.1080/16078454.2019.1599096 -
Clinical Laboratory Nov 2022Cytokine levels in patients with β-thalassemia major (β-TM) have been assessed in several studies. Accordingly, a wide variety of immune disturbances has been shown in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cytokine levels in patients with β-thalassemia major (β-TM) have been assessed in several studies. Accordingly, a wide variety of immune disturbances has been shown in patients with thalassemia. Recurrent transfusions cause iron overload, which induces an increase in the production of cytokines. However, no systematic approach or meta-analysis has been done to provide a clear feature of cytokine levels in β-TM. The present meta-analysis aimed to summarize the existing evidence regarding different levels of cytokines in patients with Β-TM compared to healthy controls.
METHODS
This study was performed according to the PRISMA checklist. A systematic search was done in Web of Science (ISI), Scopus, and PubMed databases. The quality of the included studies was assessed based on the New-castle-Ottawa Scale. Meta-analysis was run via STATA 13 software. The standardized mean difference was considered the effect size for comparing the continuous variables.
RESULTS
This meta-analysis included 16 studies conducted on 805 β-TM patients and 624 healthy individuals (with the mean age of 16.10 ± 4.33 and 16.22 ± 3.78, respectively). The results showed significantly higher levels of Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and IL-10 in patients with β-TM compared to the healthy controls.
CONCLUSION
The results indicated that the levels of both inflammatory and anti-inflammatory cytokines were higher in patients with β-TM compared to the healthy population, which could be associated with higher levels of oxidative markers in these patients. Further studies are suggested to evaluate the difference in cytokine levels among different types of thalassemia.
Topics: Humans; Child; Adolescent; Young Adult; Adult; beta-Thalassemia; Cytokines; Iron Overload; Interleukin-6; Tumor Necrosis Factor-alpha
PubMed: 36378002
DOI: 10.7754/Clin.Lab.2022.220142 -
EJHaem Jun 2024A recent evidence gaps assessment of the clinical, health-related quality of life, and economic burden associated with α-thalassemia is lacking. We conducted a...
A recent evidence gaps assessment of the clinical, health-related quality of life, and economic burden associated with α-thalassemia is lacking. We conducted a systematic literature review (SLR) following the methodological and reporting requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook for Systematic Reviews, using available literature over the past decade. This SLR identified a considerable evidence gap with regard to understanding the current burden of α-thalassemia as evident from paucity of studies published in the past 10 years. The limited data available still indicate that patients with α-thalassemia experience substantial morbidity and quality of life/economic burden that is generally comparable to patients with β-thalassemia.
PubMed: 38895066
DOI: 10.1002/jha2.882 -
The Cochrane Database of Systematic... Apr 2021Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one...
BACKGROUND
Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review.
OBJECTIVES
To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent β-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of the most recent search: 07 April 2021.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review.
MAIN RESULTS
No relevant trials were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; beta-Thalassemia
PubMed: 33880750
DOI: 10.1002/14651858.CD008708.pub5 -
Frontiers in Endocrinology 2021Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.
METHODS
Eligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
RESULTS
Fourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.
CONCLUSIONS
This is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Topics: Co-Repressor Proteins; Humans; Molecular Chaperones; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; X-linked Nuclear Protein
PubMed: 34220718
DOI: 10.3389/fendo.2021.691557 -
International Journal of Molecular... May 2024Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical... (Review)
Review
Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while variants were protective against albuminuria alone. The long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (, , and ) and nine loci were linked with eGFR (, , , , , , , , and ). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk.
Topics: Humans; Anemia, Sickle Cell; Genome-Wide Association Study; Genetic Predisposition to Disease; Kidney Diseases; Apolipoprotein L1; Disease Progression; Genes, Modifier; Glomerular Filtration Rate
PubMed: 38791464
DOI: 10.3390/ijms25105427 -
Reviews on Recent Clinical Trials May 2024β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.
BACKGROUND
β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.
OBJECTIVE
This systematic review aims to comprehensively evaluate the literature on the mechanistic effects of Silymarin on β-thalassemia outcomes in children and adolescents.
METHODS
A systematic search of electronic databases, including MEDLINE/PubMed, Embase, Scopus, Cochrane Library, and Web of Science (WOS), was done to identify relevant clinical trials before January 2024. Various data were extracted, including study characteristics, outcomes measured (hematological parameters, oxidative stress markers, iron metabolism, and other outcomes), proposed mechanisms, and safety.
RESULTS
By iron chelation effects, Silymarin can reduce reactive oxygen species (ROS) production, increase intracellular antioxidant enzyme glutathione (GSH), and insert antioxidant effects. It also attenuated inflammation through reduced tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interferon-gamma (IFNγ), C-reactive protein (CRP), interleukin 6 (IL-6), IL-17, and IL-23 levels and increase in IL-4 and IL-10 levels. By reducing iron overload conditions, Silymarin indicates modulatory effects on immune abnormalities, inhibits red blood cell (RBC) hemolysis, increases RBC count, and minimizes the need for a transfusion. Moreover, it reduces myocardial and hepatic siderosis, improves liver function tests, and modifies abnormal enzymes, particularly for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Silymarin also reduces iron overload, increases antioxidant and anti-inflammatory capacity in cardiomyocytes, and reveals antioxidant effects.
CONCLUSION
Silymarin indicates promising effects on various aspects of children and adolescents with β-thalassemia and has no serious side effects on the investigated dosage.
PubMed: 38818907
DOI: 10.2174/0115748871305325240511122602 -
The Cochrane Database of Systematic... Aug 2019Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains...
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause haemolytic anaemia by causing membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow. The life-long management of the general health effects of thalassaemia in affected individuals is a highly challenging issue in and of itself; and failure to deal with dental and orthodontic complications in people with thalassaemia exacerbates the public health, financial and personal burden posed by the condition. There exists a lack of evidence-based guidelines for care-seekers and providers to best deal with such dental and orthodontic complications in thalassaemia, which this review seeks to address.
OBJECTIVES
The main objective of this review was to assess different methods to treat dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews.Date of last search: 01 August 2019.We also searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field.Date of last search: 22 July 2019.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials for treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, gender and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened 35,202 titles from search results. We identified four unique randomised controlled trials, of which one seemed potentially relevant. Based on closer inspection, the trial was found not to be eligible for inclusion.
MAIN RESULTS
We did not find any relevant trials for inclusion in the review.
AUTHORS' CONCLUSIONS
We were unable to draw any conclusions due to the lack of available data and trials. This review highlights the need for conducting and appropriate reporting, of high-quality randomised controlled trials investigating the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia.
Topics: Humans; Malocclusion; Randomized Controlled Trials as Topic; Thalassemia; Tooth Diseases
PubMed: 31425614
DOI: 10.1002/14651858.CD012969.pub2