A Global Perspective on Milestones of Care for Children with Sickle Cell Disease

Sickle cell disease (SCD) is one of the most common severe and monogenic disorders worldwide. Acute and chronic complications deeply impact the health of children with SCD. Milestones of treatment include newborn screening, comprehensive care and prevention of cerebrovascular complications

Primary stroke prevention for sickle cell disease in north-east Italy: the role of ethnic issues in establishing a Transcranial Doppler screening program

<p>Abstract</p> <p>Background</p> <p>Stroke is a serious complication of sickle cell disease (SCD) in children. Transcranic Doppler (TCD) is a well-established predictor of future cerebrovascular symptoms: a blood flow velocity >200 cm/sec in the Middle Cerebral Artery (MCA) correlates with a high risk of stroke in cohorts of African-american HbS/HbS patients. In North-East Italy the recent increase in SCD patients is mainly due to immigration from Africa. A comprehensive care program for children with SCD was established in our Center since 2004, but a wide and routine screening for Primary stroke prevention needs to be developed.</p> <p>Methods</p> <p>In order to verify the feasibility of TCD and Transcranial color coded Sonography (TCCS) screening in our setting and the applicability of international reference values of blood velocities to our population of African immigrants with HbS/HbS SCD, we performed TCD and TCCD in 12 HbS/HbS African children and two groups of age-matched controls of Caucasian and African origin respectively. TCD and TCCS were performed on the same day of the scheduled routine hematologic visit after parental education.</p> <p>Results</p> <p>All parents accepted to perform the sonography to their children. TCD and TCCD were performed in all patients and an adequate temporal window could be obtained in all of them. Pulsatility index and depth values in both the MCA and the Basilar Artery (BA) were similar at TCD and TCCS evaluation in the three groups while time-average maximum velocities (TAMM), peak systolic velocity and diastolic velocity in the MCA and BA were higher in the patients' group on both TCD and TCCS evaluation. African and Caucasian healthy controls had similar lower values.</p> <p>Conclusion</p> <p>Our preliminary data set the base to further evaluate the implementation of a primary stroke prevention program in our setting of HbS/HbS African immigrants and HbS/beta thalassemia Italians. Parental education-preferably in the native language- on stroke risk and prevention in SCD increases compliance and should be a necessary part of the program. Ethnic background does not seem to influence TCD velocity and internationally accepted reference values already validated in African-American SCD pediatric patients can be used, but long prospective trials are needed to verify their efficacy in defining stroke risk in our setting.</p

Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

Procedural pain management in Italy: learning from a nationwide survery involving centers of the Italian Association of Pediatric Hematology-Oncology

Procedural pain is an important aspect of care in pediatrics, and particularly in pediatric oncology where children often consider this to be the most painful experience during their illness. Best recommended practice to control procedural pain includes both sedative-analgesic administration and non-pharmacological treatments, practiced in an adequate and pleasant setting by skilled staff. A nationwide survey has been conducted among the Italian Centers of Pediatric Hematology-Oncology to register operators' awareness on procedural pain, state of the art procedural pain management, operators' opinions about pain control in their center, and possible barriers impeding sedation-analgesia administration. Based on indications in the literature, we discuss the results of the survey to highlight critical issues and suggest future directions for improvement. Future objectives will be to overcome differences depending on size, improve operators' beliefs about the complexity of pain experience, and promote a global approach to procedural pain

Robot-assisted splenectomy in a teenager with chronic autoimmune thrombocytopenia

The use of the Da Vinci Xi system is gaining popularity among all surgical disciplines. A splenectomy is a treatment option for patients with hematological disorders and splenic lesions. The laparoscopic approach is nowadays the standard of care. Despite the initial controversy, recently it has been demonstrated the superiority of robotic splenectomy performed in ''difficult'' cases. We report, to our knowledge, the first case of robot-assisted splenectomy following embolization of the splenic artery in a 15-year-old patient with chronic immune thrombocytopenia, worsened by a severe cerebral sinus thrombosis, while being treated with eltrombopag and mycophenolate. Due to the need for a rapid rise in platelet counts and failure of several medical treatments, splenectomy was advocated. To raise the platelet count pre-operatively and minimize intraoperative bleeding, the embolization of the spleen artery was performed before the planned splenectomy. The intervention was carried on without any complication and at 1 year follow up the patient is in good clinical condition and has improved his neurological condition. We propose a robotic splenectomy following embolization of the splenic artery as a feasible and safe procedure. The advantages of the Da Vinci Xi system are highlighted especially in complex cases, requiring maximum precision

The opinion of clinical staff regarding painfulness of procedures in pediatric hematology-oncology: an Italian survey

<p>Abstract</p> <p>Background</p> <p>Beliefs of caregivers about patient's pain have been shown to influence assessment and treatment of children's pain, now considered an essential part of cancer treatment. Painful procedures in hematology-oncology are frequently referred by children as the most painful experiences during illness. Aim of this study was to evaluate professionals' beliefs about painfulness of invasive procedures repeatedly performed in Pediatric Hemato-Oncology Units.</p> <p>Methods</p> <p>Physicians, nurses, psychologists and directors working in Hemato-Oncology Units of the Italian Association of Pediatric Hematology-Oncology (AIEOP) were involved in a wide-nation survey. The survey was based on an anonymous questionnaire investigating beliefs of operators about painfulness of invasive procedures (lumbar puncture, bone marrow aspirate and bone marrow biopsy) and level of pain management.</p> <p>Results</p> <p>Twenty-four directors, 120 physicians, 248 nurses and 22 psychologists responded to the questionnaire. The score assigned to the procedural pain on a 0-10 scale was higher than 5 in 77% of the operators for lumbar puncture, 97.5% for bone marrow aspiration, and 99.5% for bone marrow biopsy. The scores assigned by nurses differed statistically from those of the physicians and directors for the pain caused by lumbar puncture and bone marrow aspiration. Measures adopted for procedural pain control were generally considered good.</p> <p>Conclusions</p> <p>Invasive diagnostic-therapeutic procedures performed in Italian Pediatric Hemato-Oncology Units are considered painful by all the caregivers involved. Pain management is generally considered good. Aprioristically opinions about pain depend on invasiveness of the procedure and on the professional role.</p

Tricuspid regurgitant velocity elevation in a three-year old child with sickle cell anemia and recurrent acute chest syndromes reversed not by hydroxyurea but by bone marrow transplantation

Elevated Tricuspid Regurgitant Velocity (TRV) has been related to higher mortality in adults and to hemolysis, lower oxygen saturation during 6-minute walk test and acute chest syndrome (ACS) in children with sickle cell disease (SCD). Hydroxyurea (HU) has reduced TRV value in children and adults. We describe a three year old HbSS child with recurrent ACS, hypoperfusion of the left lung, mild hemolysis and persistent TRV elevation. TRV did not normalize after HU, despite improvement in clinical conditions and in baseline laboratory parameters related to hemolysis and blood viscosity, but normalized after bone marrow transplantation (BMT). Our experience suggests that in young patients, TRV reduction can be a positive concomitant effect of BMT

Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children with sickle cell disease: Results from a long-term natural history study in Italy in the era of multimodal therapy

Background: Stroke and cerebral vasculopathy are leading causes of morbidity and mortality in patients with sickle cell disease (SCD). Transcranial Doppler (TCD) is a reliable and validated predictor of stroke risk. Children with conditional or abnormal TCD are at an increased risk for stroke, which can be mitigated by red blood cell transfusion or hydroxyurea. Elucidating the relationship between cerebral hemodynamics and hemolytic anemia can help identify novel therapeutic approaches to reduce stroke risk and transfusion dependence.Methods: This long-term, real-world study was designed to evaluate the prevalence of TCD imaging (TCDi)-assessed flow velocities in children and to interrogate their relationship with markers of anemia and hemolysis.Results: In total, 155 children (median follow-up 79.8 months, 1358.44 patient-years) had 583 evaluable TCDi results. Only patients with HbSS or HbS beta(0) had abnormal (1.6%) or conditional (10.9%) TCDi. Children with abnormal or conditional TCDi had lower hemoglobin (Hb) and higher hemolysis markers. A linear correlation was detected between TCD velocity and Hb: an Hb increase of 1 g/dL corresponded to decreases in velocity in the internal carotid and middle cerebral arteries (6.137 cm/s and 7.243 cm/s). Moreover, patients with Hb >9 g/dL presented a lower risk of TCDi-associated events.Conclusion: These results support the need to optimize disease-modifying treatments that increase Hb and reduce hemolysis for stroke prevention in young children with SCD

Distribution of HbS Allele and Haplotypes in a Multi-Ethnic Population of Guinea Bissau, West Africa: Implications for Public Health Screening

BACKGROUND: Sickle Cell Disease (SCD) is an inherited condition that is widespread globally and especially in malaria-endemic West African countries. Limited epidemiological data on SCD are available for Guinea Bissau, where newborn screening is not yet implemented, routine diagnosis is not available, and care is case directed. METHODS: Dried blood spots were collected from children accessing two hospitals managed by Italian Non-Governmental Organizations in the capital city of Bissau and sent to Padova for Hemoglobin (Hb) quantification through HPLC and molecular analysis. Beta globin gene analysis was performed in all; and Hb haplotype of the HbSS and HbSA patients was performed in South Africa. One hundred samples belonging to the most frequent ethnic groups were randomly selected for detection of G6PD mutations. RESULTS: Samples from 848 consecutive children (498 males and 350 females, mean age 6.8 years) accessing the two hospitals were analyzed: 6.95% AS (4.42% allelic frequency), 0.94% SS, and 0.23% AC. 376G G6PD allelic frequency was 24%; 14.8% in AS individuals. The Senegal haplotype was the most prevalent (31%), and the proposition of chromosomes with the atypical haplotype was surprisingly high (56%). CONCLUSION: Our study demonstrates a significant frequency of the HbS allele in the population of Guinea Bissau supporting the implementation of screening strategies. The differences among ethnic groups can help guide targeted interventions for SCD awareness campaigns and determine priority areas for public health interventions. The pilot analysis on haplotypes reveals a large proportion of the atypical haplotype, which may be indicative of a genetically heterogeneous population

Paraneoplastic Cytopenia in Ovarian Germ Cell Tumor: A Novel Presentation

We report on the case of a 12-year-old girl, who presented with an ovarian germ cell tumor and cytopenia (anemia and thrombocytopenia) as an associated paraneoplastic syndrome, which gradually regressed after the tumor's removal. This report adds to the previously described paraneoplastic syndromes potentially associated with ovarian germ cell tumor