Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with ß-thalassemia.

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.

Madrid Newborn Sickle Cell Disease Cohort: clinical outcomes, stroke prevention and survival.

In May 2003, Madrid established the universal newborn screening (NBS) for sickle cell disease (SCD). However, there are no studies resembling the evolution of a SCD neonate cohort followed according to national guidelines in Spain. The aim of this study is to describe the morbimortality and the stroke prevention programme in patients diagnosed by SCD NBS in Madrid. This is a multicentre, observational, prospective cohort study between 2003 and 2018; 187 patients diagnosed with SCD were included (151 HbSS, 6 HbSß0, 27 HbSC, 3 HbSß +), and median follow-up was 5.2 years (0.03-14.9). There were 5 deaths: 2 related to SCD in patients with severe genotype (HbSS/HbSß0). Overall survival reached 95% and SCD-related survival 96.8%. The most frequent events were fever without focus, vaso-occlusive crises and acute chest syndromes. Eight strokes occurred in 5 patients which led to a 90.7% stroke-free survival in severe genotype patients (first stroke rate, 0.54 per 100 patient-years). Transcranial Doppler (TCD) was performed in 95% of eligible patients; 75% of children with pathological TCD remained stroke-free. Regarding HbSS/HbSß0 patients, 50.1% received hydroxyurea and 9.5% haematopoietic stem cell transplantation. This study reflects the evolution of Madrid SCD cohort and provides morbimortality data similar to other developed countries.

Use of Monoclonal Antibodies in a Pediatric Patient With Severe Combined Immunodeficiency and Persistent SARS-CoV-2 Infection.

We describe the use of monoclonal antibodies for the treatment of persistent SARS-CoV-2 infection in a pediatric patient with severe combined immunodeficiency who required urgent stem cell transplantation to cure his disease.

Complete RH and Kell matching related to low alloimmunisation risk in sickle cell disease: prevalence and risk factors of alloimmunisation in a Spanish Tertiary Care National Reference Centre.

BACKGROUND: Red blood cell (RBC) transfusion remains an essential part of sickle cell disease (SCD) management but it can lead to alloimmunisation, with an increased incidence in this population. Prevention is based on RBC antigen phenotype matching, with complete RH and Kell matching being a standard of care. MATERIALS AND METHODS: We performed a retrospective, single-centre study analysing alloimmunisation prevalence and risk factors in a cohort of transfused SCD patients. RESULTS: Eighty-seven patients (96.5% of paediatric age) received 1,781 RBC units (RBCu). Complete RH and Kell matched RBCu represented a median of 100% among total transfusions per patient. Of the 87 patients, 52 (59.8%) underwent chronic transfusion therapy, whereas 35 (40.2%) were only episodically transfused. Seven patients were alloimmunised (8.4%) and eleven antibodies were detected (alloimmunisation rate: 0.62/100 units transfused). 54.6% of these antibodies corresponded to RH-Kell despite the high accomplishment of the RH-Kell matching transfusion protocol. Alloimmunised patients had a median of 90.9% RH-Kell matched transfusions vs 100% in non-alloimmunised patients, but no statistical differences were observed (p=0.127). Number of transfused RBCu (19 vs 7; p=0.023), number of episodic RBCu (8 vs 2; p=0.006), episodic to chronic RBCu ratio (0.57 vs 0.09; p=0.045), number of vaso-occlusive crises (VOC) (4 vs 2; p=0.011), and autoantibody presence (57.1 vs 0%; p<0.001) were all statistically related to alloimmunisation. DISCUSSION: We report a low alloimmunisation prevalence (8.4%) related to a high grade of RH-Kell matching. However, deviation from 100% translates into alloimmunisation, with >50% of alloantibodies corresponding to RH-Kell. Alloimmunisation risk increases with transfusion burden, particularly during acute complications, and in patients with a higher number of VOC, probably reflecting underlying inflammation and disease severity. Further studies will be needed to elucidate additional risk factors and help prevent alloimmunisation in these patients.

Actualización del registro español de hemoglobinopatías de niños y adultos / Update of the Spanish registry of haemoglobinopathies in children and adults

ANTECEDENTES Y OBJETIVO: Los pacientes con talasemia mayor (TM) y enfermedad de células falciformes (ECF) en España se han empezado a contabilizar desde la creación del registro español de hemoglobinopatías (REHem). El objetivo del trabajo es actualizar los datos publicados previamente, tras el aumento de casos por la inclusión de adultos y la introducción del cribado neonatal en casi todo el país. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, multicéntrico y ambispectivo, que incluye pacientes con hemoglobinopatías registrados en REHem, iniciado en enero de 2014 y de seguimiento anual. Los datos presentados corresponden hasta el 31 de diciembre de 2017. RESULTADOS: Se recogieron 959 pacientes. Se registraron 75 casos de talasemia (62 TM), 826 de ECF y 58 de otro tipo de hemoglobinopatías. El motivo de diagnóstico principal en la TM fue la clínica de anemia (70,6%), con una media de edad al diagnóstico de 0,7 años; en la ECF fue el cribado neonatal (33,1%), con una media de edad al diagnóstico de 2,7 años; 26 pacientes con TM (41,9%) y 30 con ECF (3,6%) fueron sometidos a trasplante. Hubo 2 fallecimientos (3,2%) con TM y 19 (2,3%) con ECF. La supervivencia global fue del 96,7% en la TM y del 97,5% en la ECF a los 15 años. CONCLUSIONES: Desde la publicación previa y tras la difusión del cribado neonatal, el método diagnóstico más frecuente, en la mayoría de comunidades autónomas, y la inclusión de pacientes adultos al registro, el REHem se ha visto incrementado en más de 240 casos, llegando hasta un total de 959 registros

BACKGROUND AND OBJECTIVE: Patients with thalassaemia major (TM) and sickle cell disease (SCD) in Spain have been counted since the creation of the Spanish registry of haemoglobinopathies (REHem). The objective of this paper is to update the published data after the increase in cases due to the inclusion of adults and introduction of new-born screening in almost the whole country. MATERIAL AND METHODS: An observational, descriptive, multicentre and ambispective study that included patients with haemoglobinopathies registered in the REHem, started in January 2014 and followed up annually. The data presented correspond until December 31, 2017. RESULTS: Nine hundred and fifty-nine patients were collected. There were 75 cases of thalassaemia (62 TM), 826 of ECF and 58 of other types of haemoglobinopathies. The main diagnostic reason in the TM cohort was anaemia symptoms (70.6%), with a mean age at diagnosis of .7 years; in the SCD cohort it was neonatal screening (33.1%), with a mean age at diagnosis of 2.7 years; 26 patients with TM (41.9%) and 30 with SCD (3.6%) underwent a transplant. There were 2 deaths (3.2%) with TM and 19 (2.3%) with SCD. Overall survival was 96.7% in the TM and 97.5% in the SCD cases at 15 years. CONCLUSIONS: Since the previous publication and after the diffusion of new-born screening, the most frequent diagnostic method, to the majority of autonomous regions, and the inclusion of adult patients to the registry, the REHem has increased by more than 240 cases, reaching a total of 959 records

Fifteen years of newborn sickle cell disease screening in Madrid, Spain: an emerging disease in a European country.

Sickle cell disease (SCD) describes a set of chronic inherited anemias characterized by hemolysis, episodes of vaso-occlusion, and high infectious risk, with high morbidity and mortality. Newborn screening (NBS) for SCD allows family health education and early start of infectious prophylaxis. In the Community of Madrid, a pilot universal NBS study found that the SCA birth prevalence was 1/5851 in newborns, higher than expected, confirming the need to include early detection in the NBS program. The aim of the present prospective single-center study is to analyze the results of newborn SCD screening in Madrid in terms of epidemiological data and its inclusion in a comprehensive care program during the last 15 years, between 1st of May 2003 and 1st of May 2018. During the study period, 1,048,222 dried bloodspots were analyzed. One hundred ninety-seven patients were diagnosed with possible SCD (HPLC phenotype of FS, FSA, FSC, FSE, FSDPunjab, FSOArab), with 187 patients finally confirmed (birth prevalence 1/5552 newborns, 0.18 per 1000 live births), and 1 out of 213 infants carried Hb S. All of them were seen by a specialist clinician; median age at the first visit consultation was 35 days and median age at the beginning of penicillin treatment was 66 days. The Madrid SCD NBS program achieved high rates of sensitivity and specificity and good quality of care assistance. Establishing a good relationship with the family, a strong education program, and a multidisciplinary team that includes social workers and a psychologist are needed to ensure the success of early intervention.

Update of the Spanish registry of haemoglobinopathies in children and adults. / Actualización del registro español de hemoglobinopatías de niños y adultos.

BACKGROUND AND OBJECTIVE: Patients with thalassaemia major (TM) and sickle cell disease (SCD) in Spain have been counted since the creation of the Spanish registry of haemoglobinopathies (REHem). The objective of this paper is to update the published data after the increase in cases due to the inclusion of adults and introduction of new-born screening in almost the whole country. MATERIAL AND METHODS: An observational, descriptive, multicentre and ambispective study that included patients with haemoglobinopathies registered in the REHem, started in January 2014 and followed up annually. The data presented correspond until December 31, 2017. RESULTS: Nine hundred and fifty-nine patients were collected. There were 75 cases of thalassaemia (62 TM), 826 of ECF and 58 of other types of haemoglobinopathies. The main diagnostic reason in the TM cohort was anaemia symptoms (70.6%), with a mean age at diagnosis of .7 years; in the SCD cohort it was neonatal screening (33.1%), with a mean age at diagnosis of 2.7 years; 26 patients with TM (41.9%) and 30 with SCD (3.6%) underwent a transplant. There were 2 deaths (3.2%) with TM and 19 (2.3%) with SCD. Overall survival was 96.7% in the TM and 97.5% in the SCD cases at 15 years. CONCLUSIONS: Since the previous publication and after the diffusion of new-born screening, the most frequent diagnostic method, to the majority of autonomous regions, and the inclusion of adult patients to the registry, the REHem has increased by more than 240 cases, reaching a total of 959 records.

Manejo y factores de riesgo de gravedad asociados a lesiones no intencionadas en urgencias de pediatría en España / Management and serious risk factors associated with unintentional injuries in paediatric emergencies in Spain

INTRODUCCIÓN: Cada año se tratan 38 millones de pacientes con lesiones en los servicios de Urgencias, siendo el 90% en forma de lesiones no intencionadas (LNI). Actualmente no existen registros globales de su manejo en España ni de los factores de riesgo que puedan llevar asociados. Nuestro objetivo es describir el manejo de las LNI en los Servicios de Urgencias Pediátricos (SUP) y analizar los factores relacionados con la presencia de lesiones graves. MATERIAL Y MÉTODOS: Subestudio de estudio observacional prospectivo multicéntrico desarrollado durante 12 meses en 11 SUP de hospitales de la Red de Investigación de la Sociedad Española de Urgencias Pediátricas (RiSEUP-SPERG), incluyéndose niños de 0 a 16 años de edad que consultan por una LNI, los días 13 de cada mes. Se registraron datos epidemiológicos, circunstancias de la lesión y datos sobre la atención en el SUP y destino al alta. RESULTADOS: Se registraron 10.175 episodios, de los que 1.941 fueron LNI (19,1%). Se incluyeron 1.673, de los cuales 257 (15,4%) fueron graves. La prueba complementaria realizada más frecuentemente fue la radiografía simple (60,0%) y el procedimiento más frecuente fue la inmovilización de extremidad (38,6%). Se encontró asociación significativa entre presentar una LNI grave y la edad > 5 años (OR 2,24; IC 95%: 1,61-3,16), el antecedente de fractura (OR 2,05; IC 95%: 1,22-3,43) o la actividad deportiva como mecanismo lesional (OR 1,76; IC 95%: 1,29-2,38), entre otros. CONCLUSIÓN: En España, la mayoría de los casos de LNI no son graves. Las radiografías y la inmovilización de extremidades son las pruebas y procedimientos más frecuentemente realizados. La LNI grave se asoció con factores individuales, como la edad > 5 años o el antecedente de fractura, y con la actividad deportiva como mecanismo asociado a gravedad. Resulta vital implementar medidas para mejorar la prevención de estas lesiones y apoyar la capacitación de los cuidadores mediante programas educacionales

INTRODUCTION: Thirty-eight million patients with injuries are treated in Emergency Departments every year, 90% of them being in the form of unintentional injuries (UIs). There are currently no global records of its management in Spain, or the risk factors that may be associated with them. The objective of this study is to describe the management of UIs in Spanish paediatric emergency departments, and to analyse factors related to the presence of serious injuries. MATERIAL AND METHODS: A sub-study of a prospective multicentre observational study conducted over 12 months in 11 hospitals of the Spanish Paediatric Emergency Research Group (RiSEUP-SPERG), including children from 0 to 16 years of age consulting for UIs. Epidemiological data, circumstances of the injury, and data on emergency care and discharge destination were recorded on the 13 th day of each month. RESULTS: A total of 10,175 episodes were recorded, of which 1,941 were UIs (19.1%), including 1,673, of which 257 (15.4%) were severe. The most frequent complementary test was simple radiography (60.0%), and the most frequent procedure was limb immobilisation (38.6%). A significant relationship was found between presenting with a severe UI and age > 5 years (OR 2.24; 95% CI: 1.61-3.16), history of fracture (OR 2.05; 95% CI: 1.22-3.43), or sports activity as a mechanism of injury (OR 1.76; 95% CI: 1.29-2.38), among others. CONCLUSION: In Spain, most UIs are not serious. X-rays and immobilisation of extremities are the most frequently performed tests and procedures. Severe UIs were associated with individual factors, such as age > 5 years or history of fracture, and with sports activity as a mechanism associated with severity. It is vital to implement measures to improve the prevention of these injuries and to support the training of caregivers through educational programmes

Evaluation of the effectiveness of prophylactic oral vitamin D (cholecalciferol) in children with sickle cell disease.

BACKGROUND: Vitamin D (25(OH)D) deficiency has become an emerging public health problem due to its influence on skeletal and extraskeletal diseases. Bone health in patients with sickle cell disease (SCD) is especially compromised and they are more likely to have 25(OH)D deficiency than the general population. Despite this, there is little information on the efficacy of vitamin D3 (vitD3) prophylaxis and its role in improving bone mineral density (BMD) in this population. PROCEDURES: A prospective, longitudinal, single-center study was conducted with 136 children with SCD monitored at a tertiary referral hospital for SCD. Demographic, clinical and management data, 25(OH)D levels and bone densitometries (DXA) were collected. RESULTS: Eighty patients were included. There are significant differences between the means of each of 25(OH)D levels as a function of whether the patient started prophylactic treatment as an infant or not (35.71 vs. 27.89 ng/ml, respectively [p = .014]). In multivariate analysis, 800 IU daily dose was shown as a protective factor (p = .044) to reach optimal blood levels (≥30 ng/ml). According to Kaplan-Meier curves, patients younger than 10 years reached optimal levels earlier than older (p = .002), as well as those who were not being treated with hydroxyurea (p = .039). CONCLUSIONS: VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥30 ng/ml, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health.

[Management and serious risk factors associated with unintentional injuries in paediatric emergencies in Spain]. / Manejo y factores de riesgo de gravedad asociados a lesiones no intencionadas en urgencias de pediatría en España.

INTRODUCTION: Thirty-eight million patients with injuries are treated in Emergency Departments every year, 90% of them being in the form of unintentional injuries (UIs). There are currently no global records of its management in Spain, or the risk factors that may be associated with them. The objective of this study is to describe the management of UIs in Spanish paediatric emergency departments, and to analyse factors related to the presence of serious injuries. MATERIAL AND METHODS: A sub-study of a prospective multicentre observational study conducted over 12months in 11hospitals of the Spanish Paediatric Emergency Research Group (RiSEUP-SPERG), including children from 0 to 16years of age consulting for UIs. Epidemiological data, circumstances of the injury, and data on emergency care and discharge destination were recorded on the 13th day of each month. RESULTS: A total of 10,175 episodes were recorded, of which 1,941 were UIs (19.1%), including 1,673, of which 257 (15.4%) were severe. The most frequent complementary test was simple radiography (60.0%), and the most frequent procedure was limb immobilisation (38.6%). A significant relationship was found between presenting with a severe UI and age >5 years (OR2.24; 95%CI: 1.61-3.16), history of fracture (OR2.05; 95%CI: 1.22-3.43), or sports activity as a mechanism of injury (OR1.76; 95%CI: 1.29-2.38), among others. CONCLUSION: In Spain, most UIs are not serious. X-rays and immobilisation of extremities are the most frequently performed tests and procedures. Severe UIs were associated with individual factors, such as age >5years or history of fracture, and with sports activity as a mechanism associated with severity. It is vital to implement measures to improve the prevention of these injuries and to support the training of caregivers through educational programmes.

Consultas relacionadas con lesiones no intencionadas en urgencias en España: serie de casos / Emergency department consultations associated with unintentional injuries: A cases series

OBJETIVO: Analizar las características clínico-epidemiológicas de los niños que consultan en urgencias por una lesión no intencionada (LNI) en España. MÉTODOS: Serie de casos multicéntrica con recogida de datos prospectiva desarrollada durante 12 meses, en los servicios de urgencias pediátricos (SUP) de 11 hospitales pertenecientes a la Red de Investigación de la Sociedad Española de Urgencias Pediátricas. La recogida de datos comenzó entre septiembre de 2014 y enero de 2015, continuando durante un año en todos los servicios de urgencias pediátricos, incluyéndose los niños de 0 a 16 años que consultaron por LNI. RESULTADOS: Durante el estudio se registraron 10.175 episodios, de los que 1.941 correspondieron a LNI (19,1%, IC 95%: 18,3-19,8%), incluyéndose 1.673 en el estudio. Las caídas, traumatismos directos y las lesiones derivadas de actividades deportivas constituyeron más del 80%, observándose variaciones significativas del mecanismo lesional en diferentes grupos de edad. Más de la mitad se produjeron en casa o en el colegio. En el 39% la LNI no fue presenciada por un adulto. El diagnóstico más frecuente fue traumatismo de extremidades (63,0%), objetivándose una fractura en 242 (14,4% de las LNI). Ingresaron 34 (2,0%) pacientes, sobre todo para reducción quirúrgica de fracturas (21, el 61,8% del total de ingresos). No se registraron fallecimientos en las primeras 24 h. CONCLUSIONES: Las LNI constituyen un motivo muy frecuente de consulta en urgencias en España. El conocimiento de las circunstancias que rodean a estas LNI ayudaría a desarrollar medidas preventivas adecuadas y mejorar la capacitación de las personas, sanitarias o no, que pueden participar en la atención a estos niños

OBJECTIVE: To analyse the clinical and epidemiological characteristics of children who are attended in Emergency Departments (EDs) for an unintentional injury in Spain. METHODS: Multicentre case series with prospective data collection conducted during 12 months in the ED of 11 hospitals belonging to the Spanish Paediatric Emergency Research Group. Data were collected between September 2014 and January 2015, continuing for one year in all paediatric EDs, and included children between 0 and 16 years old seen for an unintentional injury. RESULTS: A total of 10,175 episodes were recorded during the study, of which 1,941 were due to unintentional injuries (19.1%, 95% CI: 18.3%-19.8%), and 1,673 of these were included in the study. Falling, direct injuries, and injuries due to sports activities represented more than 80%, with significant variations in the injuries mechanism observed in different age groups. More than occurred at home or school. About 40% of the unintentional injuries were not witnessed by an adult. The most frequent diagnosis was limb trauma (63.0%), with a fracture being observed in 242 (14.4% of unintentional injuries). As regards fractures, 34 (2.0%) were admitted to hospital, with 21 (61.8%) for surgical reduction of the fracture. No deaths were recorded in the first 24 h. CONCLUSIONS: Unintentional injuries constitute a very common reason for consultation in EDs in Spain. The circumstances surrounding the unintentional injuries should be considered, in order to develop preventive measures and to improve the training of people involved in the care of these children

[Emergency department consultations associated with unintentional injuries: A cases series]. / Consultas relacionadas con lesiones no intencionadas en urgencias en España: serie de casos.

OBJECTIVE: To analyse the clinical and epidemiological characteristics of children who are attended in Emergency Departments (EDs) for an unintentional injury in Spain. METHODS: Multicentre case series with prospective data collection conducted during 12 months in the ED of 11 hospitals belonging to the Spanish Paediatric Emergency Research Group. Data were collected between September 2014 and January 2015, continuing for one year in all paediatric EDs, and included children between 0 and 16 years old seen for an unintentional injury. RESULTS: A total of 10,175 episodes were recorded during the study, of which 1,941 were due to unintentional injuries (19.1%, 95% CI: 18.3%-19.8%), and 1,673 of these were included in the study. Falling, direct injuries, and injuries due to sports activities represented more than 80%, with significant variations in the injuries mechanism observed in different age groups. More than occurred at home or school. About 40% of the unintentional injuries were not witnessed by an adult. The most frequent diagnosis was limb trauma (63.0%), with a fracture being observed in 242 (14.4% of unintentional injuries). As regards fractures, 34 (2.0%) were admitted to hospital, with 21 (61.8%) for surgical reduction of the fracture. No deaths were recorded in the first 24h. CONCLUSIONS: Unintentional injuries constitute a very common reason for consultation in EDs in Spain. The circumstances surrounding the unintentional injuries should be considered, in order to develop preventive measures and to improve the training of people involved in the care of these children.

DICER1 mutation and tumors associated with a familial tumor predisposition syndrome: practical considerations.

The familial tumor predisposition syndrome known as DICER1-pleuropulmonary blastoma (PPB) or DICER1 tumor predisposition syndrome was first described in 2009, and it involves an increased risk in the occurrence of various tumors, like cystic nephroma and PPB. Here is presented a girl with a cystic nephroma and two cystic lung lesions who was diagnosed years later with the DICER1 gene mutation. This mutation was also found in one of her parents. Thus, the screening for the DICER1 gene mutation may be important in children with certain/multiple tumors and their families.