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1.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469764

RESUMO

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.


Assuntos
Hemoglobinopatias , Hemoglobinas Anormais , Feminino , Humanos , Criança , Saturação de Oxigênio , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Oximetria , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/análise , Oxigênio , Gasometria
2.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474150

RESUMO

Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the ß-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Talassemia , Talassemia beta , Humanos , Densidade Óssea , Hemoglobinopatias/genética , Anemia Falciforme/genética , Hemoglobina Falciforme , Talassemia beta/genética
4.
Indian J Pathol Microbiol ; 67(1): 115-120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358199

RESUMO

Introduction: Beta thalassemia and hemoglobin (HbE)-related hemoglobinopathies are common public health problems in developing countries. High-performance liquid chromatography (HPLC) is currently the diagnostic test of choice for carrier detection, but it is costly. Hence, some initial screening and complementary tests are required, which can be affordable. Aims: To find out the distribution of different red blood cell (RBC) indices in beta thalassemia trait (BTT) and HbE-related hemoglobinopathies and to determine their significance as screening tests to distinguish between these hemoglobinopathies. Study Settings and Design: This observational cross-sectional study has been carried out at an NABL (National Accreditation Board for Testing and Calibration Laboratories)-accredited Laboratory of Eastern India with approval from the concerned Institutional Ethics Committee from January 2021 to March 2021. Methods and Material: : HPLC tests and complete hemograms were performed on 2247 ethylenediaminetetraacetic acid anti-coagulated blood samples over 3 months. Patients <1 year of age or having a history of blood transfusion within the past 06 months were excluded. Statistical Analysis: : One-way analysis of variance along with Bonferroni post-hoc test was performed to find out significant differences of means of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin%, red blood cell (RBC) count, and red cell distribution width (RDW-CV) among concerned hemoglobinopathies. Results: The results show a significant difference of total RBC count, RDW, MCV, MCH, and MCHC between BTT and E-trait. No significant difference of mean was found between HbE homozygous and E-beta. E-trait differs from both HbE homozygous and E-beta significantly in three parameters, namely, RDW, MCV and MCH. A value of MCV at ≤73.8 fl and MCH at ≤21.9 pg may be a clue of diagnosis for BTT rather than E-trait with >90% sensitivity and >80% specificity. Conclusion: RBC indices vary significantly between BTT and other HbE-related hemoglobinopathies. They can specially be utilized to differentiate BTT and E-trait as supportive tests in addition to the gold standard test of HPLC.


Assuntos
Hemoglobinopatias , Talassemia beta , Humanos , Lactente , Índices de Eritrócitos , Estudos Transversais , Hemoglobinopatias/diagnóstico , Hemoglobinas , Índia , Eritrócitos
5.
mBio ; 15(3): e0316923, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38323831

RESUMO

Malaria parasites have adaptive mechanisms to modulate their intracellular redox status to tolerate the enhanced oxidizing effects created by malaria fever, hemoglobinopathies and other stress conditions, including antimalaria drugs. Emerging artemisinin (ART) resistance in Plasmodium falciparum is a complex phenotype linked to the parasite's tolerance of the activated drug's oxidative damage along with changes in vesicular transport, lipid metabolism, DNA repair, and exported proteins. In an earlier study, we discovered that many of these metabolic processes are induced in P. falciparum to respond to the oxidative damage caused by artemisinin, which exhibited a highly significant overlap with the parasite's adaptive response mechanisms to survive febrile temperatures. In addition, there was a significant overlap with the parasite's survival responses to oxidative stress. In this study, we investigated these relationships further using an in vitro model to evaluate if oxidative stress and heat-shock conditions could alter the parasite's response to artemisinin. The results revealed that compared to ideal culture conditions, the antimalarial efficacy of artemisinin was significantly reduced in parasites growing in intraerythrocytic oxidative stress but not in heat-shock condition. In contrast, heat shock significantly reduced the efficacy of lumefantrine that is an important ART combination therapy partner drug. We propose that prolonged exposure to intraerythrocytic microenvironmental oxidative stress, as would occur in endemic regions with high prevalence for sickle trait and other hemoglobinopathies, can predispose malaria parasites to develop tolerance to the oxidative damage caused by antimalarial drugs like artemisinin. IMPORTANCE: Emerging resistance to the frontline antimalarial drug artemisinin represents a significant threat to worldwide malaria control and elimination. The patterns of parasite changes associated with emerging resistance represent a complex array of metabolic processes evident in various genetic mutations and altered transcription profiles. Genetic factors identified in regulating P. falciparum sensitivity to artemisinin overlap with the parasite's responses to malarial fever, sickle trait, and other types of oxidative stresses, suggesting conserved inducible survival responses. In this study we show that intraerythrocytic stress conditions, oxidative stress and heat shock, can significantly decrease the sensitivity of the parasite to artemisinin and lumefantrine, respectively. These results indicate that an intraerythrocytic oxidative stress microenvironment and heat-shock condition can alter antimalarial drug efficacy. Evaluating efficacy of antimalarial drugs under ideal in vitro culture conditions may not accurately predict drug efficacy in all malaria patients.


Assuntos
Anemia Falciforme , Antimaláricos , Artemisininas , Antagonistas do Ácido Fólico , Hemoglobinopatias , Malária Falciparum , Malária , Humanos , Antimaláricos/farmacologia , Plasmodium falciparum/genética , Artemisininas/farmacologia , Malária Falciparum/tratamento farmacológico , Malária/tratamento farmacológico , Lumefantrina/farmacologia , Lumefantrina/uso terapêutico , Combinação de Medicamentos , Proteínas de Protozoários/genética , Antagonistas do Ácido Fólico/farmacologia , Estresse Oxidativo , Hemoglobinopatias/tratamento farmacológico , Anemia Falciforme/tratamento farmacológico , Resistência a Medicamentos/genética
6.
Biosensors (Basel) ; 14(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38392002

RESUMO

Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world population. Among various Hb disorders, approximately 1.5% of the world population carries ß-thalassemia (ß-Thal), affecting 40,000 newborns every year. Early screening and a timely diagnosis are essential for ß-thalassemia patients for the prevention and management of later clinical complications. However, in Africa, Southern Europe, the Middle East, and Southeast Asia, where ß-thalassemia is most prevalent, the diagnosis and screening for ß-thalassemia are still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, which is a paper-based microchip electrophoresis platform that enables the first point-of-care diagnostic test for ß-thalassemia. We evaluated the accuracy of Gazelle for the ß-Thal screening across 372 subjects in the age range of 4-63 years at Apple Diagnostics lab in Mumbai, India. Additionally, 30 blood samples were prepared to mimic ß-Thal intermediate and ß-Thal major samples. Gazelle-detected levels of Hb A, Hb F, and Hb A2 demonstrated high levels of correlation with the results reported through laboratory gold standard high-performance liquid chromatography (HPLC), yielding a Pearson correlation coefficient = 0.99. This ability to obtain rapid and accurate results suggests that Gazelle may be suitable for the large-scale screening and diagnosis of ß-Thal.


Assuntos
Antílopes , Hemoglobinopatias , Talassemia beta , Recém-Nascido , Humanos , Animais , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Cromatografia Líquida de Alta Pressão
7.
BMC Med Genomics ; 17(1): 9, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167091

RESUMO

BACKGROUND: People with autosomal recessive disorders often were born without awareness of the carrier status of their parents. The American College of Medical Genetics and Genomics (ACMG) recommends screening 113 genes known to cause autosomal recessive and X-linked conditions in couples seeking to learn about their risk of having children with these disorders to have an appropriate reproductive plan. METHODS: We analyzed the exome sequencing data of 1,642 unrelated Thai individuals to identify the pathogenic variant (PV) frequencies in genes recommended by ACMG. RESULTS: In the 113 ACMG-recommended genes, 165 PV and likely PVs in 60 genes of 559 exomes (34%, 559/1642) were identified. The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added. The carrier rate was still as high as 14.7% when thalassemia and hemoglobinopathies were excluded. In addition to thalassemia, hemoglobinopathies, and G6PD deficiency, carrier frequencies of > 1% were found for Gaucher disease, primary hyperoxaluria, Pendred syndrome, and Wilson disease. Nearly 2% of the couples were at risk of having offsprings with the tested autosomal recessive conditions. CONCLUSIONS: Based on the study samples, the expanded carrier screening, which specifically targeted common autosomal recessive conditions in Thai individuals, will benefit clinical outcomes, regarding preconception/prenatal genetic carrier screening.


Assuntos
Hemoglobinopatias , Talassemia , Criança , Gravidez , Feminino , Humanos , Tailândia , Sequenciamento do Exoma , Exoma , Hemoglobinopatias/genética , Talassemia/genética
8.
Orphanet J Rare Dis ; 19(1): 22, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254184

RESUMO

Pain is an hallmark of sickle-cell-related acute clinical manifestations as part of acute vaso-occlusive crisis (VOC). In SCD pain has different origins such as vascular or neuropathic pain, which requires multimodal analgesia. This is based on the administration of drugs with different pharmacological mechanisms of action, maximizing analgesia and minimizing their adverse events and the risk of drug-addition in patients experiencing acute-recurrent pain events as in SCD. Ketorolac is a potent non-narcotic analgesic, being relatively safe and effective during pain-management in children and adults. Up to now, there is a lack of safety information on continuous infusion ketorolac as used to control acute pain in patients with SCD, and the benefits/risks ratio needs to be investigated. Here, we report for the first time the safety profile of ketorolac in the special population of patients with SCD. We confirmed that ketorolac in combination with tramadol, an opioid like molecule, is effective in pain control of adult patients with SCD experiencing acute severe VOCs defined by pain visual analog scale. Our study shows that short term (72 h) continuous infusion of ketorolac plus tramadol is not associated with adverse events such as liver or kidney acute disfunction or abnormalities in coagulation parameters during patients' hospitalization and within 30 days after patients discharge. This is extremely important for patients with SCD, who should have access to multimodal therapy to control recurrent acute pain crisis in order to limit central sensitization a fearsome issue of undertreated recurrent acute pain and of chronic pain.


Assuntos
Dor Aguda , Analgesia , Anemia Falciforme , Hemoglobinopatias , Tramadol , Adulto , Criança , Humanos , Cetorolaco/uso terapêutico , Dor Aguda/tratamento farmacológico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico
9.
Br J Haematol ; 204(3): 1054-1060, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38195958

RESUMO

We report a large series of 40 patients presenting EPAS1-mutated paraganglioma (PGL) in whom we investigated a cause underlying chronic hypoxia. Four patients suffered from hypoxaemic heart disease. In patients with available haemoglobin electrophoresis results, 59% presented with a haemoglobin disorder, including six with sickle cell disease, five with sickle cell trait and two with heterozygous haemoglobin C disease. Histological and transcriptomic characterization of EPAS1 tumours revealed increased angiogenesis and high similarities with pseudohypoxic PGLs caused by VHL gene mutations. Sickle haemoglobinopathy carriers could thus be at increased risk for developing EPAS1-PGLs, which should be taken into account in their management and surveillance.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hemoglobinopatias , Paraganglioma , Humanos , Hemoglobinas/genética , Hipóxia/genética , Mutação , Paraganglioma/genética , Paraganglioma/patologia
10.
Blood Transfus ; 22(2): 111-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37235738

RESUMO

BACKGROUND: Hemoglobinopathies are a group of diseases that include those due to globin gene mutations, such as thalassemia major (TM) and thalassemia intermedia (TI) or due to alteration of hemoglobin structure such as sickle cell disease (SCD), as well as a combination of these conditions such as thalasso-drepanocytosis (TD). They constitute the most frequent hereditary anemias requiring blood transfusion. MATERIALS AND METHODS: In April 2022, a questionnaire was sent to the Transfusion Services (TS) of Sicily, Sardinia and the Maltese National Blood Transfusion (MNBT) service. The questionnaire was divided into a generic part including the number of patients followed and the type of hemoglobinopathy, and a section relating to transfusion therapy, including the number of units transfused, whether red blood cells (RBC) were washed and, finally, a section relating to the presence or absence of alloantibodies and their identification. RESULTS: Data was retrieved for 2,574 patients: 68.6% TM, 15.4% TI, 10.3% TD, 4.1% SCD, and 1.6% other hemoglobinopathies (OHA). The number of RBC units transfused was 76,974, equivalent to 24.5% of all the RBCU transfused from the total number of patients followed. The number of washed RBCU was 21.1% of all the units used; 337 patients (37%) were diagnosed with alloantibodies, the majority of which were patients with SCD (20.6%). Of the 485 alloantibodies found, 90.3% were identified. The antibodies found most frequently were related to the Kell system (41.7%) followed by antibodies to the Rhesus system (37.9%); 29.7% of patients had more than one antibody. DISCUSSION: From our study, certain indications can be formulated: complete the National Registry for patients with hemoglobinopathies; create a Registry of alloimmunized patients to ensure transfusion therapy is as safe as possible, considering antibody evanescence; and 3) increase the recruitment of blood donors of diverse ethnicities.


Assuntos
Anemia Hemolítica Autoimune , Anemia Falciforme , Hemoglobinopatias , Talassemia beta , Humanos , Isoanticorpos , Sicília/epidemiologia , Malta , Eritrócitos , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/terapia , Transfusão de Sangue , Anemia Falciforme/terapia
11.
Clin Chim Acta ; 552: 117685, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38030031

RESUMO

Hemoglobin (Hb) abnormalities, such as thalassemia and structural Hb variants, are among the most prevalent inherited diseases and are associated with significant mortality and morbidity worldwide. However, there were not comprehensive reviews focusing on different clinical analytical techniques, research methods and artificial intelligence (AI) used in clinical screening and research on hemoglobinopathies. Hence the review offers a comprehensive summary of recent advancements and breakthroughs in the detection of aberrant Hbs, research methods and AI uses as well as the present restrictions anddifficulties in hemoglobinopathies. Recent advances in cation exchange high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), isoelectric focusing (IEF), flow cytometry, mass spectrometry (MS) and polymerase chain reaction (PCR) etc have allowed for the definitive detection by using advanced AIand portable point of care tests (POCT) integrating with smartphone microscopic classification, machine learning (ML) model, complete blood counts (CBC), imaging-based method, speedy immunoassay, and electrochemical-, microfluidic- and sensing-related platforms. In addition, to confirm and validate unidentified and novel Hbs, highly specialized genetic based techniques like PCR, reverse transcribed (RT)-PCR, DNA microarray, sequencing of genomic DNA, and sequencing of RT-PCR amplified globin cDNA of the gene of interest have been used. Hence, adequate utilization and improvement of available diagnostic and screening technologies are important for the control and management of hemoglobinopathies.


Assuntos
Hemoglobinopatias , Hemoglobinas Anormais , Talassemia , Humanos , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/análise , Inteligência Artificial , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinas/análise , Focalização Isoelétrica , Cromatografia Líquida de Alta Pressão
12.
Br J Haematol ; 204(1): 26-28, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37877454

RESUMO

Accurate laboratory screening for sickle cell disease and other haemoglobin disorders is expanding worldwide. Two new reports describe different methods and strategies for screening in Mali and Denmark, respectively, and their encouraging results suggest that countries should tailor their screening programmes according to local needs, resources and opportunities. Commentary on: Guindo et al. Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: a comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood. Br J Haematol 2024;204:337-345 and Gravholt et al. The Danish national haemoglobinopathy screening programme: report from 16 years of screening in a low-prevalence, non-endemic region. Br J Haematol 2024;204:329-336.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Recém-Nascido , Humanos , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Triagem Neonatal/métodos , Sangue Fetal , Hemoglobinas
13.
Br J Haematol ; 204(1): 68-73, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37932940

RESUMO

For this paper, cases reported formally and anecdotally to the authors in their screening and diagnostic roles have been selected to demonstrate areas where errors have occurred, and caution should be exercised. The cases demonstrate that it is vital that the performance and limitations of the techniques used, along with the phenotypic presentation of cases where haemoglobin variants and/or thalassaemias are coinherited are understood by those performing result interpretation. Those who deliver the service as well as those who receive reports and give results and counselling should be aware of the complexity of the topic.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Talassemia , Humanos , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Anemia Falciforme/diagnóstico
14.
Intern Med J ; 54(2): 290-294, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37449655

RESUMO

BACKGROUND: In the last few decades, the life expectancy of patients with transfusion-dependent thalassaemia (TDT) and sickle cell disease (SCD) has improved significantly, in part because of improved iron chelation. Fertility challenges and pregnancy complications have historically limited reproductive options in this group; however, improved multi-disciplinary care has made infertility a chronic disease complication requiring attention. Despite this, there are very few reports and no Australian data describing fertility and pregnancy outcomes in this population. AIMS: To identify the rate of assisted reproductive technologies (ART) utilisation in our female transfusion-dependent haemoglobinopathy patients and to establish the nature of maternal and neonatal complications in this cohort. METHODS: A 20-year retrospective analysis (1997-2017) at an Australian centre captured data on conception rates, use of assisted reproductive techniques (ART), and pregnancy and neonatal outcomes in female transfusion-dependent haemoglobinopathy patients. RESULTS: Conception was attempted in 14 women (11 TDT and three SCD) during the study period. A total of 28 pregnancies resulting in 25 live births were recorded. ART supported 13 conceptions. A positive association was not identified between elevated mean serum ferritin and ART use; however, all patients with an established diagnosis of hypogonadotropic hypogonadism (HH) required ART. Maternal complications included gestational diabetes mellitus and post-partum haemorrhage. There were no cardiac complications. Two-thirds of women underwent lower segment caesarean section, with prematurity complicating 20% of births. There were no neonatal or maternal deaths. CONCLUSION: Pregnancy is an achievable goal for women with transfusion-dependent haemoglobinopathies, although the support of ART may be required in a subset of patients.


Assuntos
Cesárea , Hemoglobinopatias , Recém-Nascido , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Austrália/epidemiologia , Técnicas de Reprodução Assistida , Resultado da Gravidez/epidemiologia , Hemoglobinopatias/complicações , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/terapia
15.
Br J Haematol ; 204(1): 329-336, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37694757

RESUMO

The Danish national haemoglobinopathy screening programme seeks to determine parental haemoglobinopathy carrier state antenatally. In this retrospective register-based study, we evaluated the 16-year trajectory of this programme, utilising the Danish Red Blood Cell Centre's laboratory database, covering approximately 77% of the Danish population. During the study period, we observed a substantial increase in annual diagnostic examinations performed, from 389 in 2007 to 3030 in 2022. Women constituted 88% of these cases, aligning with the emphasis of the screening programme. Of these, 54% of women of reproductive age (15-40 years) and 10% of women >40 years were specified as pregnant. During our study period, 61 children were born with a severe haemoglobinopathy, out of which 23 children were born from mothers not residing in Denmark during their first trimester thus not included in the screening programme. Prenatal invasive testing was performed for 60 fetuses, identifying 12 with homozygous or compound heterozygous haemoglobinopathy. The Danish haemoglobinopathy screening programme has provided screening, information and reproductive choices for numerous families. During the study period, screening for haemoglobinopathies has been steadily increasing and is expected to continue to increase. Awareness of and adherence to the screening programme is subject of further investigation and optimisation.


Assuntos
Hemoglobinopatias , Criança , Gravidez , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Prevalência , Estudos Retrospectivos , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Inquéritos e Questionários , Dinamarca/epidemiologia
16.
Br J Haematol ; 204(2): 668-676, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37786398

RESUMO

We evaluated the impact of peer reviews in driving improvement in healthcare quality for people with haemoglobinopathy in the United Kingdom. We analysed compliance to four Quality Standards (QS)-based peer reviews from 2010 to 2020 to evaluate its impact in driving healthcare quality. Seventeen paediatric and 29 adult haemoglobinopathy centres were reviewed in 2010/11 and 2012/13 respectively; 33 paediatric and 33 adult centres were reviewed in 2014/16, and 32 paediatric and 32 adult centres were reviewed in 2018/2020. Compliance with QS and participant feedback were analysed to assess the impact of peer review programmes to drive improvement in quality of care. We noted that haemoglobinopathy centres significantly improved their compliance to QS between the first two review programmes, but not in the final review programme. In comparison to other disease-group reviews, the haemoglobinopathy departments were less able to address critical peer review recommendations in their own institutions. The peer review programme was unable to drive sustained improvement in healthcare quality, underscoring the need for sustained development and support for haemoglobinopathy services in the National Health Service. Further work is needed to understand why disparities exist among peer review-driven improvement initiatives within different disease groups.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Talassemia , Adulto , Humanos , Criança , Medicina Estatal , Reino Unido , Hemoglobinas
17.
Unfallchirurgie (Heidelb) ; 127(2): 146-150, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-37270730

RESUMO

The vaso-occlusive crises of sickle cell disease are accompanied by bone necrosis, which favors endogenous bacterial colonization and thus osteomyelitis. This poses a major challenge for eradication and fracture management.A 22-year-old patient with sickle cell disease sustained a multifragmentary, humeral shaft fracture. During surgical management, pus drained from the fracture site and further diagnostic work-up revealed osteomyelitis with evidence of Klebsiella aerogenes. Septicemia due to Klebsiella aerogenes had been treated 5 months prior to the accident, which occured because of a vaso-occlusive crisis. This is associated with clustered bone necrosis and endogenous germ colonization. Eradication of the germs and fracture care become a challenge. Repeated surgical procedures with segmental transfer can be a successful treatment option.


Assuntos
Anemia Falciforme , Doenças Transmissíveis , Fraturas Espontâneas , Hemoglobinopatias , Osteomielite , Osteonecrose , Humanos , Adulto Jovem , Adulto , Anemia Falciforme/complicações , Doenças Transmissíveis/complicações , Osteomielite/complicações , Osteonecrose/complicações , Fraturas Espontâneas/complicações , Hemoglobinopatias/complicações
18.
Blood Cells Mol Dis ; 104: 102758, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37246072

RESUMO

The genetic regulation of hemoglobin is complex and there are a number of genetic abnormalities that result in clinically important hemoglobin disorders. Here, we review the molecular pathophysiology of hemoglobin disorders and review both old and new methods of diagnosing these disorders. Timely diagnosis of hemoglobinopathies in infants is essential to coordinate optimal life-saving interventions, and accurate identification of carriers of deleterious mutations allows for genetic counseling and informed family planning. The initial laboratory workup of inherited disorders of hemoglobin should include a complete blood count (CBC) and peripheral blood smear, followed by carefully selected tests based on clinical suspicion and available methodology. We discuss the utility and limitations of the various methodologies to fractionate hemoglobin, including cellulose acetate and citrate agar hemoglobin electrophoresis, isoelectric focusing, high-resolution high-performance liquid chromatography, and capillary zone electrophoresis. Recognizing that most of the global burden of hemoglobin disorders exists in low- and middle-income countries, we review the increasingly available array of point-of-care-tests (POCT), which have an increasingly important role in expanding early diagnosis programs to address the global burden of sickle cell disease, including Sickle SCAN, HemoTypeSC, Gazelle Hb Variant, and Smart LifeLC. A comprehensive understanding of the molecular pathophysiology of hemoglobin and the globin genes, as well as a clear understanding of the utility and limitations of currently available diagnostic tests, is essential in reducing global disease burden.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Humanos , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinas/genética , Anemia Falciforme/genética , Focalização Isoelétrica/métodos
20.
Cells ; 12(24)2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38132168

RESUMO

Therapy via the gene addition of the anti-sickling ßAS3-globin transgene is potentially curative for all ß-hemoglobinopathies and therefore of particular clinical and commercial interest. This study investigates GLOBE-based lentiviral vectors (LVs) for ßAS3-globin addition and evaluates strategies for an increased ß-like globin expression without vector dose escalation. First, we report the development of a GLOBE-derived LV, GLV2-ßAS3, which, compared to its parental vector, adds anti-sickling action and a transcription-enhancing 848-bp transcription terminator element, retains high vector titers and allows for superior ß-like globin expression in primary patient-derived hematopoietic stem and progenitor cells (HSPCs). Second, prompted by our previous correction of HBBIVSI-110(G>A) thalassemia based on RNApol(III)-driven shRNAs in mono- and combination therapy, we analyzed a series of novel LVs for the RNApol(II)-driven constitutive or late-erythroid expression of HBBIVSI-110(G>A)-specific miRNA30-embedded shRNAs (shRNAmiR). This included bifunctional LVs, allowing for concurrent ßAS3-globin expression. LVs were initially compared for their ability to achieve high ß-like globin expression in HBBIVSI-110(G>A)-transgenic cells, before the evaluation of shortlisted candidate LVs in HBBIVSI-110(G>A)-homozygous HSPCs. The latter revealed that ß-globin promoter-driven designs for monotherapy with HBBIVSI-110(G>A)-specific shRNAmiRs only marginally increased ß-globin levels compared to untransduced cells, whereas bifunctional LVs combining miR30-shRNA with ßAS3-globin expression showed disease correction similar to that achieved by the parental GLV2-ßAS3 vector. Our results establish the feasibility of high titers for LVs containing the full HBB transcription terminator, emphasize the importance of the HBB terminator for the high-level expression of HBB-like transgenes, qualify the therapeutic utility of late-erythroid HBBIVSI-110(G>A)-specific miR30-shRNA expression and highlight the exceptional potential of GLV2-ßAS3 for the treatment of severe ß-hemoglobinopathies.


Assuntos
Hemoglobinopatias , Talassemia beta , Humanos , Talassemia beta/genética , Talassemia beta/terapia , Interferência de RNA , Terapia Genética/métodos , Vetores Genéticos/genética , Hemoglobinopatias/genética , Hemoglobinopatias/terapia , Mutação , Globinas beta/genética , RNA Interferente Pequeno/genética
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