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Pediatric patients with sickle cell disease and thalassemia major present clinical characteristics that could lead to a higher incidence of central venous access devices-associated complications (CVAD-C). With the objective of analyzing the safety of the use of CVAD in these patients, a retrospective review including all pediatric patients with these pathologies who required the implantation of a CVAD between 2004 and 2019 was performed. In all, 54 patients with 100 CVAD (65 totally implantable venous access port with subcutaneous reservoir, 35 single-lumen or double-lumen partially tunneled catheter) were included. During 60,410 days at risk of suffering a CVAD-C, 55 complications (complication rate [CR]/1000 catheter-days at risk=0.91) were reported in 46 CVAD: 19 mechanicals (CR=0.32), 32 infectious (CR=0.53), and 4 thrombotic complications (CR=0.066). Incidence of mechanical and infectious complications was significantly higher in double-lumen partially tunneled catheter than in totally implantable venous access port with subcutaneous reservoir (P

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.

Resumen Antecedentes y objetivo Los pacientes con talasemia mayor (TM) y enfermedad de celulas falciformes (ECF) en Espana se han empezado a contabilizar desde la creacion del registro espanol de hemoglobinopatias (REHem). El objetivo del trabajo es actualizar los datos publicados previamente, tras el aumento de casos por la inclusion de adultos y la introduccion del cribado neonatal en casi todo el pais. Material y metodos Estudio observacional, descriptivo, multicentrico y ambispectivo, que incluye pacientes con hemoglobinopatias 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 hemoglobinopatias. El motivo de diagnostico principal en la TM fue la clinica de anemia (70,6%), con una media de edad al diagnostico de 0,7 anos; en la ECF fue el cribado neonatal (33,1%), con una media de edad al diagnostico de 2,7 anos; 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 anos. Conclusiones Desde la publicacion previa y tras la difusion del cribado neonatal, el metodo diagnostico mas frecuente, en la mayoria de comunidades autonomas, y la inclusion de pacientes adultos al registro, el REHem se ha visto incrementado en mas de 240 casos, llegando hasta un total de 959 registros.

Background: Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. Methods: Patients

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.

Introduction: Symptomatic venous thromboembolism (VTE) is diagnosed in 3%14% of patients during pediatric acute lymphoblastic leukemia (ALL) therapy. There are well-known risk factors, but the role of others as inherited thrombophilia is still controversial. Prophylaxis with low molecular weight heparin (LMWH) has been described, but its use is not globally accepted. Methods: A retrospective multicentric study in ALL patients 1-18 years old following SEHOP-PETHEMA-2013 treatment guideline was performed to evaluate VTE rate, anticoagulant treatment, outcome, risk factors, and safety and usefulness of LMWH administration as primary thromboprophylaxis in children with inherited thrombophilia. Results: A total of 652 patients were included in the study. VTE incidence was 8.7%. Most of the cases occurred during induction therapy associated with central venous catheter. Univariant analysis showed that family history of thrombosis, presence of mediastinal mass, high-risk treatment group, and inherited thrombophilia were statistically significant risk factors. LMWH administration seemed to decrease VTE rate in patients with inherited thrombophilia and those with T-cell ALL phenotype. Conclusion: Most of the VTE cases occurred in patients without inherited thrombophilia, but when it is present, the VTE risk is higher. LMWH administration was useful to decrease VTE in these patients.

Severe bacterial infections (SBI) have become less frequent in children with sickle cell disease (SCD) in the last decades. However, because of their potential risk of SBI, they usually receive empirical therapy with broad-spectrum antibiotics when they develop fever and are hospitalized in many cases. We performed a prospective study including 79 SCD patients with fever [median age 4.1 (1.7–7.5) years, 78.5% males; 17 of the episodes were diagnosed with SBI and 4 of them were confirmed] and developed a risk score for the prediction of SBI. The optimal score included CRP > 3 mg/dl, IL-6 > 125 pg/ml and hypoxemia, with an AUC of 0.91 (0.83–0.96) for the prediction of confirmed SBI and 0.86 (0.77–0.93) for possible SBI. We classified the patients in 3 groups: low, intermediate and high risk of SBI. Our risk-score based management proposal could help to safely minimize antibiotic treatments and hospital admissions in children with SCD at low risk of SBI.

Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p Conclusion We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

Resumen: Objetivo: Describir las características clínico-epidemiológicas, el manejo y el seguimiento de las sospechas de maltrato infantil diagnosticadas en Urgencias Pediátricas. Métodos: Estudio observacional, unicéntrico, y retrospectivo realizado entre 2008 y 2017. Se recogieron datos clínicos, epidemiológicos y de seguimiento de los menores de 16 años diagnosticados de sospecha de maltrato. Se realizó un análisis descriptivo y analítico, bivariante y multivariante. Resultados: Se consideró potencial maltrato en 404 pacientes de 570.648 urgencias atendidas (0,07%). El maltrato físico fue el más frecuente (40,3%). La mediana de edad fue 4,3 años (RIC 1,6-10,2). El 55% fueron niñas, siendo en ellas más frecuente el abuso sexual (OR 3,71; IC95%: 2,23-6,17), y el maltrato físico más común en varones (OR 1,72; IC95%: 1,15-2,57). Un total de 89 pacientes (22%) precisaron ingreso. La edad y el tipo de maltrato se relacionaron de forma independiente con el riesgo de hospitalización. El 56,4% precisó seguimiento adicional; el análisis multivariable mostró mayor seguimiento por Salud Mental en los casos de abuso sexual (OR 3,98; IC95%: 1,93-7,03) y maltrato emocional (OR 4,93; IC95%: 1,82-13,35), y por servicios sociales en los maltratos físicos (OR: 4,39; IC95%: 1,61-11,98). Conclusiones: En el presente estudio, el maltrato infantil es más frecuente en preescolares. La edad y el tipo de maltrato predicen la necesidad de hospitalización. El tipo de seguimiento está condicionado por el tipo de maltrato padecido. Abstract: Objective: To describe the clinical and epidemiological features, management, and follow-up of child abuse suspicions diagnosed in the Paediatric Emergency Unit. Methods: A single-centre, observational and retrospective study was conducted between 2008 and 2017. Clinical, epidemiological and follow-up data were collected in those patients younger than 16 that were reported as child abuse suspicions. A descriptive and analytic study was performed, as well as a bivariate and multivariate analysis. Results: A total of 404 out of 570,648 emergency patients (0.07%) were diagnosed with potential abuse. Physical abuse was the most frequent kind of abuse (40.3%). The median age was 4.3 years (IQR 1.6-10.2), and 55% were girls, with sexual abuse being more common in them (OR 3.71; 95% CI: 2.23-6.17), and physical abuse more frequent in boys (OR 1.72; 95% CI: 1.15-2.57). A total of 89 patients (22%) required admission. Age and type of abuse were independently associated with risk of admission. More than half (56%) of the cases required additional follow-up, with sexual (OR 3.98; 95% CI: 1.93-7.03) and emotional abuse (OR 4.93; 95% CI: 1.82-13.35) requiring more mental health follow-up, and physical abuse requiring more social services follow-up (OR 4.39; 95% CI: 1.61-11.98). Conclusions: In our study, child abuse is more frequent in pre-school children. Age and type of abuse are associated with the need of admission. The kind of follow-up is determined by the type of abuse.

Pulse oximetry in a 15-month-old boy with cyanosis revealed low oxygen saturation (SpO2 60%) with normal echocardiography findings. Arterial blood gas analysis showed normal PaO2, low hemoglobin oxygen saturation, and high methemoglobin level. Blood analysis revealed mild hemolytic anemia. HPLC and electrophoresis showed a variant hemoglobin in the A2-window and C/E band respectively. Beta-globin gene sequencing revealed heterozygous hemoglobin M Saskatoon [Beta63 (E7) His > Tyr; HBB: c 190C > T] along with alpha + heterozygous thalassemia. Hemoglobins M are structural variants that stabilize heme iron in the oxidized (ferric) state. They can be confused with other causes of methemoglobinemia like genetic alterations in methemoglobin reductase enzyme systems of red cells. The prognosis is excellent in these non-life-threatening conditions. : HbM, a variant of hemoglobin, should be considered in the differential diagnosis of cyanosis and pseudo-cyanosis (brown coloration), once cardiorespiratory pathologies are ruled out. Keywords: Methemoglobinemia, Hemoglobin M, Pulse oximetry, Hemoglobin oxygen saturation, Pseudo-cyanosis

Severe bacterial infections (SBI) have become less frequent in children with sickle cell disease (SCD) in the last decades. However, because of their potential risk of SBI, they usually receive empirical therapy with broad-spectrum antibiotics when they develop fever and are hospitalized in many cases. We performed a prospective study including 79 SCD patients with fever [median age 4.1 (1.7–7.5) years, 78.5% males; 17 of the episodes were diagnosed with SBI and 4 of them were confirmed] and developed a risk score for the prediction of SBI. The optimal score included CRP > 3 mg/dl, IL-6 > 125 pg/ml and hypoxemia, with an AUC of 0.91 (0.83–0.96) for the prediction of confirmed SBI and 0.86 (0.77–0.93) for possible SBI. We classified the patients in 3 groups: low, intermediate and high risk of SBI. Our risk-score-based management proposal could help to safely minimize antibiotic treatments and hospital admissions in children with SCD at low risk of SBI. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01702-w.

Catheter-related bacteriemia by Cupriavidus spp. is a rare condition with very few cases reported in the literature. Most of them occurred in immunocompromised patients.To report a case of recurrent catheter-related bacteriemia by Cupriavidus pauculus in an immunocompromised infant in order to analyze possible therapeutic options, especially in relation to the need or not for central venous catheter (CVC) removal.22-month-old infant with B-cell acute lymphoblas tic leukemia (ALL) in reinduction phase, CVC carrier. He presented to the Emergency Room with fever without focus on examination. Blood tests were performed (without increase of acute phase reactants) and differential blood cultures (peripheral and CVC). He was hospitalized and empirical antibiotic therapy was started with intravenous fourth-generation cephalosporin (cefepime). After 24 hours, blood cultures were positive for Cupriavidus pauculus, growing first in the CVC culture. We maintained cefepime, adding catheter lock therapy with ciprofloxacin. Afterward, the infection was resolved, allowing us to keep the CVC. Seven months later, in the context of fever, Cupriavidus pauculus was again identified in CVC blood culture. We decided this time to remove the catheter, in addition to the administration of intravenous cefepime. The patient has not presented new episodes nine months after de removal of the CVC.Catheter-related bacteremia by Cupriavidus is a rare condition in children that usually occurs in immunocompromised patients. Catheter lock therapy associated with systemic antibiotics could be a safe option in patients with difficult CVC re moval. However, if persistent colonization of the CVC is suspected, it may be necessary to remove it.

BACKGROUND The use of azoles for antifungal prophylaxis after familial allogeneic stem cell transplantation in children (SCT) is hindered by adverse events and drug interactions especially in children affected by sickle cell disease. Intermittent, higher dose of micafungin could be an alternative. METHODS A prospective, observational, longitudinal, single-center study was conducted between May 2015 and June 2018. The study included 30 patients between 2 and 18 years old who underwent allogeneic SCT and received prophylaxis with micafungin on alternating days after the bone marrow engraftment phase. FINDINGS Fifty transplants performed, 30 included prophylaxis against IFIs, with micafungin in an alternating pattern according to the previously described protocol. The indication for HSCT was hemoglobinopathies in 76.7%, acute leukemia in 20.0% and Fanconi anemia in 3.3%. The prophylaxis duration was 2.33 months (1.53 to 3.98). In our study, 40.0% (12/30) of the patients had acute GVHD, and 6.7% (2/30) had chronic GVHD, which prolonged the duration of alternating prophylaxis. No serious adverse effects of the use of micafungin were observed in any of the patients. There was also no breakthrough Invasive fungal infection (IFI) during alternating prophylaxis. CONCLUSION: In selected patients, micafungin was well tolerated without breakthrough IFI in our study.

Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47 center dot 6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non-haematological toxicity. The 12-month overall survival and event-free survival rates were 50 center dot 8 +/- 26 center dot 4% and 38 center dot 9 +/- 25 center dot 3% with blinatumomab, 45 center dot 8 +/- 26% and 27 center dot 5 +/- 25% with inotuzumab.

Background: Since the beginning of SARS-CoV-2 pandemic, it has been widely recognized that children and adolescents seem to have milder clinical courses as compared to adult counterparts. However, there is concern that vulnerable collectives including pediatric patients treated for cancer or under immunosuppression may be at higher risk. Methods: We retrospectively collected Spanish COVID-19 cases in children and adolescents with solid and hematological malignancies, non-malignant chronic hematologic conditions, and post allogeneic-stem cell transplantation, from the beginning of the pandemic on January 31 to April 24, 2020. Results: We included 47 cases with RT-PCR positive COVID-19 from 41 centers in Spain, where 97.6% of pediatric patients are treated for cancer. In most cases (76.6%), infection was asymptomatic, or symptoms were mild. Severe illness was observed in 14.9% of cases with respiratory distress and/or hypoxemia, and 8.5% required admission to the PICU. Symptomatic patients received supportive care associated with antiviral and immunomodulatory agents depending upon severity. Anticancer therapy was withhold in the majority of cases during the infection course. Most patients recovered from COVID-19. Two deaths were reported. Conclusion: In our cohort, most children receiving anticancer chemotherapy presented a mild clinical course and had a good outcome. Highly immunosuppressed patients with major comorbidities were at higher risk of severe infections. Among this fragile collective, individualized expert discussion is critical for anti-infectious therapy and appropriate anticancer treatment.

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%; p50% 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.

Las infecciones por Cupriavidus spp. son poco frecuentes, especialmente en niños, causando infecciones en inmunodeprimidos o portadores de dispositivos intravasculares. Objetivo: Presentar un caso de bacteriemia recurrente relacionada con catéter por Cupriavidus pauculus en un paciente pediátrico para analizar posibles opciones terapéuticas, especialmente en relación con la necesidad o no de retirada de catéter venoso central (CVC). Caso Clínico: Niño de 22 meses con leucemia linfoblástica aguda (LLA) tipo B en fase de reinducción, portador de un CVC. Consultó en Servicio de Urgencias por fiebre sin foco, sin elevación de reactantes de fase aguda. Se hospitalizó con antibioterapia intravenosa empírica con cefalosporina de 4ª generación (cefepime). En los hemocultivos diferenciales (sangre periférica y CVC) se identificó Cupriavidus pauculus, creciendo primero en el cultivo del CVC. Se mantuvo antibioterapia sistémica sin cambios y se iniciaron sellados del catéter con ciprofloxacino. La evolución fue favorable, resolviéndose la infección y permitiendo conservar el catéter. Siete meses después el paciente presentó otro episodio de fiebre sin foco, aislándose nuevamente Cupriavidus pauculus en el hemocultivo del CVC. En esta ocasión, además de cefepime intravenoso, se decidió retirar el CVC. Tras 9 meses de la retirada del CVC, no ha presentado nuevos episodios. Conclusión: Las infecciones por Cupriavidus spp. son raras en pediatría. El tratamiento sistémico asociado a sellados del CVC podría ser una opción segura en pacientes estables con dificultad para la retirada del catéter; aunque, ante la sospecha de colonización persistente del catéter, puede ser necesaria su retirada.

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, FSD

The aim of this study was to describe the characteristics of vaso-occlusive crises (VOC) in children with sickle cell disease and to identify factors associated with greater severity. We performed a prospective observational study from August 2012 to January 2014. The study population comprised patients with sickle cell disease who consulted at the emergency department (ED) for VOC. We recorded demographic variables, history of complications related to the disease, and data on usual treatment. We also assessed pain, analgesia at home, need for admission, length of stay, and analgesia during admission. Analytical parameters were collected. A total of 29 patients with VOC were included. The patient's usual treatment was hydroxyurea (HU) in 69.0%, and 7.0% required chronic transfusions. In the ED, 90.0% had moderate or severe pain, even though 86.0% had received analgesia at home (41.4% minor opioids). Overall, 27 of the 29 patients were admitted, and 56.0% needed major opioids. Higher lactate dehydrogenase (LDH) levels were related to the use of major opioids during admission (p = 0.038). A significant difference was recorded between the median number of days of admission for patients receiving non-steroidal anti-inflammatory drugs and for those requiring intravenous opioids (p = 0.005). Most patients with VOC were admitted to hospital. Lactate dehydrogenase level in the ED was a predictor of severity and was associated with the need for major opioids during admission and more days of admission.

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.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.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.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.

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.

Resumen: Introducción: Clostridium difficile es la principal causa de diarrea nosocomial en adultos, y su incidencia está aumentado en los últimos años. Es difícil determinar su impacto en niños debido a las altas tasas de colonización. Material y métodos: Estudio retrospectivo en menores de 15 años ingresados con diarrea a lo largo de un año. Se estudiaron las características epidemiológicas, clínicas, analíticas y la evolución de los niños con infección por Clostridium difficile (ICD) en comparación con otros aislamientos. Los factores predictores de ICD fueron determinados mediante análisis multivariante. Resultados: Se identificaron 250 niños con diarrea, realizándose estudio microbiológico completo en 174. En 79 (45,4%) se llegó al diagnóstico: 25,6% ICD (n = 19; 13 enterotoxigénicos); 28,6% otras bacterias (n = 21) y 45,8% virus (n = 34; rotavirus n = 31; adenovirus n = 3). Un 68,4% fueron menores de 2 años, y un 15,8% fueron adquiridos en la comunidad. En comparación con otras causas de diarrea, la ICD se asoció a comorbilidad (p

Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two-day Pan-European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus-based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes., SCOPUS: ar.j, info:eu-repo/semantics/published

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.

Background Familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6 are distinct neurological disorders associated with mutations in the CACNA1A gene. Phenotypic variability and clinical overlap are recognized. Patients We describe a 2-year-old child with transiently decreased consciousness and clinical and radiological signs of early-onset cerebellar atrophy. The family history was significant, and 11 affected members across four generations indicated an unusually wide clinical spectrum including migraine, hemiplegia, coma, and progressive cerebellar ataxia. Results The p.Thr666Met mutation of the CACNA1A gene was identified in the index patient and in five of his affected relatives who were analyzed. Our patient is the youngest one of this entity diagnosed to date. Conclusions Taking into account such a wide clinical expression of these gene mutations, it could be more accurate to speak about "channel-related diseases" to characterize the clinical expression according to the genetic analysis and to the phenotypes associated with each CACNA1A gene mutation.

Background Heterotopias are a neuronal migration disorder caused by extrinsic factors or by genetic mutations. When the location is periventricular, the most frequent genetic cause is the mutation in the "filamin A2 gene" , which is X-linked. New genes for periventricular nodular heterotopia with an autosomal inheritance pattern have been recently discovered. Patients We describe two siblings. The girl, who was prenatally diagnosed ventriculomegaly, had delayed development. At 6 months, she had no head control and variable muscle tone, alternating low axial tone with jerking movements. She became microcephalic. Magnetic resonance imaging at 12 months of age revealed enlarged lateral ventricles, periventricular nodular heterotopia, thin corpus callosum, a T 2 -hyperintensity of the putamen and the thalamus, and a loss of volume of lenticular nucleus. At 18 months, she developed sporadic myoclonic seizures that were well controlled with valproic acid. Her younger brother also developed progressive microcephaly and psychomotor delay by 6 months. He exhibited axial hypotonia with a prominent dystonic-athetoid component. Magnetic resonance imaging at 15 months of age revealed asymmetric ventriculomegaly plus diffuse nodules lining the temporal horns, a thin corpus callosum, and hyperintensity signal in putamens. He had no seizures. Results Because of the association of microcephaly, developmental delay with dystonic movements, the imaging results, and the probable autosomal recessive inheritance pattern, genetic analysis was requested. This detected a homozygous nonsense mutation in ARFGEF2 gene, at the DNA level c.388C>T in exon 4. Conclusions The presence of dyskinetic movements in individuals with acquired microcephaly could be a manifestation of periventricular nodular heterotopia due to ARFGEF2 mutation.