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Archives of Osteoporosis Nov 2021Multiple observational studies have reported high prevalence of fracture in patients with thalassemia. However, most of these studies have included limited number of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple observational studies have reported high prevalence of fracture in patients with thalassemia. However, most of these studies have included limited number of patients, and only few of them have reported prevalence of fracture among patients with different types and severity of thalassemia.
OBJECTIVE
This systematic review and meta-analysis was conducted to summarize all available data of fracture prevalence among patients with thalassemia.
METHODS
A systematic review was conducted using EMBASE and MEDLINE databases from inception to June 2021 to determine studies that reported prevalence of fracture in thalassemia patients. The pooled prevalence with 95% confidence interval (95%CI) of fracture across studies was determined using a random-effect, generic inverse variance method.
RESULTS
After two rounds of systematic review, a total of 25 studies with 4934 patients were included in the meta-analysis. The pooled prevalence of fracture among patients with thalassemia was 16% (95%CI, 15-17%, I = 94.3%). The subgroup analyses showed that the pooled prevalence of fracture was 4% (95%CI, 2-6%; I = 70.4%) among patients with alpha thalassemia, 17% (95%CI, 16-19%; I = 93.2%) among patients with beta thalassemia, 18% (95%CI, 16-19%; I = 89.0%) among patients with transfusion-dependent thalassemia, and 7% (95%CI, 4-10%; I = 94.2%) among patients with non-transfusion-dependent thalassemia.
CONCLUSION
Fracture is common in patients with thalassemia, and may be more prevalent in beta thalassemia and transfusion-dependent thalassemia than in alpha thalassemia and non-transfusion-dependent thalassemia.
Topics: Fractures, Bone; Humans; Prevalence; Thalassemia; beta-Thalassemia
PubMed: 34773506
DOI: 10.1007/s11657-021-01026-0 -
Obstetrics and Gynecology Dec 2021To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops.
OBJECTIVE
To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops.
DATA SOURCES
PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases were searched using the following keywords: "fetus" OR "foetal" OR "fetal" OR "foetus" AND "ascites" from inception to February 2020. The search was limited to the English language.
METHODS OF STUDY SELECTION
A total of 1,983 articles were identified through the search strategy. All studies containing five or more cases of isolated fetal ascites were included.
TABULATION, INTEGRATION, AND RESULTS
Eleven studies, involving 315 cases of isolated fetal ascites, were eligible for inclusion in this systematic review. All included studies were evaluated using the tool for evaluating the methodologic quality of case reports and case series described by Murad et al. Data were summarized using narrative review and descriptive statistics. Two-tailed Fisher exact P values calculated from hypergeometric distribution were used to compare outcome by etiology. CIs were calculated with Clopper-Pearson exact binomial interval. The etiologies of isolated fetal ascites are genitourinary (24%), gastrointestinal (20%), viral or bacterial infections (9%), cardiac (9%), genetic disorders not otherwise categorized (8%), chylous ascites (6%), metabolic storage disorders (3%), other structural disorders (4%), other causes (4%) and idiopathic (13%). Survival is most favorable for cases of isolated fetal ascites as a result of chylous (100%), idiopathic (90%), gastrointestinal (77%) and genitourinary (77%) etiologies. Survival is least favorable for fetuses with isolated fetal ascites as a result of structural disorders (25%), cardiac etiology (32%) and metabolic storage disorders (33.3%). When pregnancy terminations were excluded, survival rates were similar between fetuses diagnosed at or after 24 weeks of gestation compared with those diagnosed at less than 24 weeks (74% vs 61%, P=.06). Progression of fetal ascites to fetal hydrops occurred in 6.6% (95% CI 3.6-9.6%) (17/259) of cases when pregnancies that were terminated were excluded.
CONCLUSION
Isolated fetal ascites has a diverse etiology. Outcome is related to the etiology of isolated fetal ascites. In the majority of cases, fetal ascites does not progress to fetal hydrops.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42020213930.
Topics: Ascites; Disease Progression; Female; Fetal Death; Fetal Diseases; Gestational Age; Humans; Hydrops Fetalis; Pregnancy; Pregnancy Outcome; Survival Rate
PubMed: 34735407
DOI: 10.1097/AOG.0000000000004605 -
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 -
Leukemia Research Dec 2021
Topics: Genetic Diseases, X-Linked; Humans; Myelodysplastic Syndromes; Myeloproliferative Disorders; alpha-Thalassemia
PubMed: 34325177
DOI: 10.1016/j.leukres.2021.106670 -
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 -
Clinical Genetics Nov 2021We performed a systematic review of the literature to evaluate the incidence and types of lysosomal storage disorders (LSD) in case series of nonimmune hydrops fetalis... (Meta-Analysis)
Meta-Analysis
We performed a systematic review of the literature to evaluate the incidence and types of lysosomal storage disorders (LSD) in case series of nonimmune hydrops fetalis (NIHF). PubMed, Ovid, and clinicaltrials.gov were reviewed for case series evaluating the workup of NIHF diagnosed in utero or in the neonatal period in human subjects from 1979 to August 2020. Retrospective case series with at least five cases of fetal and/or neonatal NIHF with its workup mentioned were identified. Idiopathic NIHF was defined as NIHF without an apparent cause after initial standard-of-care workup. In total, 22 case series with 2678 total cases of NIHF were identified. The overall incidence of LSD was 6.6% (177/2663) in NIHF cases that were tested for any LSD, and 8.2% (177/2151) in idiopathic NIHF cases. The most common LSD identified in cases of NIHF were mucopolysaccharidosis type VII, galactosialidosis, infantile sialic acid storage disease, Gaucher disease, GM1 gangliosidosis, and sialidosis. More than 40% of the most common LSD causes of NIHF have a potential postnatal treatment. LSD testing for NIHF allows for early diagnosis, better counseling and appropriate management, planning for possible early treatment, and counseling for recurrence risk.
Topics: Animals; Biomarkers; Clinical Decision-Making; Disease Management; Disease Susceptibility; Female; Genetic Predisposition to Disease; Humans; Hydrops Fetalis; Lysosomal Storage Diseases; Molecular Diagnostic Techniques; Pregnancy
PubMed: 34057202
DOI: 10.1111/cge.14005 -
Annals of Human Biology Jun 2021Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of...
CONTEXT
Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of mutations and the prevalence of thalassaemia, but findings are often contradictory.
OBJECTIVE
This systematic review aimed to provide a comprehensive view of the prevalence of thalassaemia-associated mutations in different countries, their effect on haemoglobin (Hb) levels, as well as reporting thalassaemia-associated rare mutations.
METHODS
A systematic search of the literature was carried out through major indexing databases (MEDLINE/PubMed, Scopus, EMBASE, Cochrane central, and ISI web of science) using keywords: "Co-inheritance, αα, β, thalassaemia" and "α-β thalassaemia, Mediterranean anemia, mutations" from 1998-September 2019. Hand-searching was also performed. There was no language restriction.
RESULTS
The initial searches yielded 1059 studies, of which 92 articles were included following inclusion and exclusion criteria. Of these, 3.3% (3) of articles were cohort studies, and 96.7% (89) of the remaining articles were cross-sectional studies. Our findings showed that 45.6% (42) of researchers investigated β-thalassaemia, 22.9% (21) αα-β thalassaemia, and 31.5% (29) α thalassaemia.
CONCLUSION
The present study provides valuable information about the spectrum of thalassaemia-associated mutations, which can be useful for preventing thalassaemia, reducing costs of care, reducing the treatment-related side effects, and showing the most defective mutations.HighlightEvaluating the increase or decrease in the birth prevalence of thalassaemiaIdentifying the most common and rare mutations in various parts of the worldComparing researchers' findings from various parts of the world.
Topics: Humans; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 34032183
DOI: 10.1080/03014460.2021.1909135 -
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 -
Ultrasound in Obstetrics & Gynecology :... Oct 2021To determine the incremental yield of exome sequencing (ES) over chromosomal microarray analysis (CMA) or karyotyping in prenatally diagnosed non-immune hydrops fetalis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the incremental yield of exome sequencing (ES) over chromosomal microarray analysis (CMA) or karyotyping in prenatally diagnosed non-immune hydrops fetalis (NIHF).
METHODS
A prospective cohort study (comprising an extended group of the Prenatal Assessment of Genomes and Exomes (PAGE) study) was performed which included 28 cases of prenatally diagnosed NIHF undergoing trio ES following negative CMA or karyotyping. These cases were combined with data from a systematic review of the literature. MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched electronically (January 2000 to October 2020) for studies reporting on the incremental yield of ES over CMA or karyotyping in fetuses with prenatally detected NIHF. Inclusion criteria for the systematic review were: (i) at least two cases of NIHF undergoing sequencing; (ii) testing initiated based on prenatal ultrasound-based phenotype; and (iii) negative CMA or karyotyping result. The incremental diagnostic yield of ES was assessed in: (i) all cases of NIHF; (ii) isolated NIHF; (iii) NIHF associated with an additional fetal structural anomaly; and (iv) NIHF according to severity (i.e. two vs three or more cavities affected).
RESULTS
In the extended PAGE study cohort, the additional diagnostic yield of ES over CMA or karyotyping was 25.0% (7/28) in all NIHF cases, 21.4% (3/14) in those with isolated NIHF and 28.6% (4/14) in those with non-isolated NIHF. In the meta-analysis, the pooled incremental yield based on 21 studies (306 cases) was 29% (95% CI, 24-34%; P < 0.00001; I = 0%) in all NIHF, 21% (95% CI, 13-30%; P < 0.00001; I = 0%) in isolated NIHF and 39% (95% CI, 30-49%; P < 0.00001; I = 1%) in NIHF associated with an additional fetal structural anomaly. In the latter group, congenital limb contractures were the most prevalent additional structural anomaly associated with a causative pathogenic variant, occurring in 17.3% (19/110) of cases. The incremental yield did not differ significantly according to hydrops severity. The most common genetic disorders identified were RASopathies, occurring in 30.3% (27/89) of cases with a causative pathogenic variant, most frequently due to a PTPN11 variant (44.4%; 12/27). The predominant inheritance pattern in causative pathogenic variants was autosomal dominant in monoallelic disease genes (57.3%; 51/89), with most being de novo (86.3%; 44/51).
CONCLUSIONS
Use of prenatal next-generation sequencing in both isolated and non-isolated NIHF should be considered in the development of clinical pathways. Given the wide range of potential syndromic diagnoses and heterogeneity in the prenatal phenotype of NIHF, exome or whole-genome sequencing may prove to be a more appropriate testing approach than a targeted gene panel testing strategy. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; High-Throughput Nucleotide Sequencing; Humans; Hydrops Fetalis; Karyotyping; Microarray Analysis; Predictive Value of Tests; Pregnancy; Prenatal Diagnosis; Prospective Studies; Exome Sequencing
PubMed: 33847422
DOI: 10.1002/uog.23652 -
The Journal of Maternal-fetal &... Oct 2022Mirror syndrome is a rare disease associated with high fetal mortality of up to 67.2%. It is thought to be underdiagnosed and is often associated with preeclampsia.... (Review)
Review
INTRODUCTION
Mirror syndrome is a rare disease associated with high fetal mortality of up to 67.2%. It is thought to be underdiagnosed and is often associated with preeclampsia. Mirror syndrome is characterized by "triple edema": generalized maternal, placental, and fetal edema.
OBJECTIVE
This comprehensive review aims to thoroughly summarize the existing data and provide a broad update on the topic to help accurate diagnosis and encourage further research.
METHODS
A comprehensive search of several databases (Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) was conducted.
RESULTS
The last systematic review of mirror syndrome cases was conducted in 2016 and included 113 patients. Much is still unknown about the pathophysiology of the disease and it remains underdiagnosed.
CONCLUSIONS AND RELEVANCE
Mirror syndrome is likely more prevalent than current data suggests for it is often misdiagnosed as pre-eclampsia. The differential of Mirror syndrome should be considered in anomalous presentations of pre-eclampsia as intervention may save the fetus and improve maternal symptoms. It is important to further the study on the pathophysiology of the disease to better understand, diagnose and potentially treat it, to avoid its high morbidity and mortality.
Topics: Edema; Female; Humans; Hydrops Fetalis; Placenta; Pre-Eclampsia; Pregnancy; Syndrome; Systematic Reviews as Topic
PubMed: 33722118
DOI: 10.1080/14767058.2020.1844656