Nomenclature and definition in asymmetric regional body overgrowth.

We designate a novel term "isolated lateralized overgrowth" (ILO) for the findings previously described as "isolated hemihypertrophy" and "isolated hemihyperplasia." ILO is defined as lateralized overgrowth in the absence of a recognized pattern of malformations, dysplasia, or morphologic variants. ILO is likely genetically heterogeneous. Further study is required to determine more of the underlying genetic etiologies and potential associations with currently unrecognized patterns of malformation.

Pediatric emergency room activities in Italy: a national survey.

BACKGROUND: In Italy, the number of accesses to the Emergency Units has been growing for the past 30 years. This, together with a low coordination between hospital and peripheral pediatric services, has brought to an unnecessarily high number of hospital admissions. For this reason, it is essential to plan and implement strategies able to improve the appropriateness of hospital admissions. In the '90s, the Short Stay Observation was extended to pediatric patients. As highlighted by the report "Guidelines for Pediatric Observation Units" (2005), patients receive considerable benefits from a short hospital permanence. The purpose of the study is to report data about the Pediatric Emergency Room activities in Italy. METHODS: In 2011, the Italian Society of Pediatrics promoted an online data collection to investigate organization and activity of Italian Pediatric and Neonatal Units. A form, containing 140 questions, was sent to 624 Pediatric and Neonatology Units. This study will be focused only on data regarding pediatric Emergency Rooms (E.R.) and Observation Units. RESULTS: 237 units replied, 183 if we focus on units with pediatric inpatient service. Based on the results, E.R Units were provided with a dedicated pediatrician in 56 % of the cases: of these, 85 % for 24 h. The majority of the patients were seen by a pediatrician. In only 8 % of the units, patients visited by a pediatrician were less than 40 %. The age limit was 14 years in 60 % of the cases. In 72 % of participating units a E.R. triage was carried out. Only 18 % of units registered more than 10000 E.R. visits/year. The percentage of children hospitalized after accessing the E.R. was significantly higher in southern regions (more than 20 % of the units hospitalized more than 40 % of children entering the E.R.). 66 % of the units were provided with an Observation Unit. In 61 % of the cases, the duration did not exceed 24 h. In more than half of the structures, less than 10 % of the E.R. visits went into observation. The type of remuneration was not homogeneous. CONCLUSIONS: The study highlights the heterogeneity of the Italian reality, with great possibilities for improvement, especially in southern regions.

Chromosome anomalies in bone marrow as primary cause of aplastic or hypoplastic conditions and peripheral cytopenia: disorders due to secondary impairment of RUNX1 and MPL genes.

BACKGROUND: Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS. RESULTS: Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2-8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT). CONCLUSIONS: A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias.

Invariant NKT cell reconstitution in pediatric leukemia patients given HLA-haploidentical stem cell transplantation defines distinct CD4+ and CD4- subset dynamics and correlates with remission state.

Immune reconstitution plays a crucial role on the outcome of patients given T cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (hHSCT) for hematological malignancies. CD1d-restricted invariant NKT (iNKT) cells are innate-like, lipid-reactive T lymphocytes controlling infections, cancer, and autoimmunity. Adult mature iNKT cells are divided in two functionally distinct CD4(+) and CD4(-) subsets that express the NK receptor CD161 and derive from thymic CD4(+)CD161(-) precursors. We investigated iNKT cell reconstitution dynamics in 33 pediatric patients given hHSCT for hematological malignancies, with a follow-up reaching 6 y posttransplantation, and correlated their emergence with disease relapse. iNKT cells fully reconstitute and rapidly convert into IFN-γ-expressing effectors in the 25 patients maintaining remission. CD4(+) cells emerge earlier than the CD4(-) ones, both displaying CD161(-) immature phenotypes. CD4(-) cells expand more slowly than CD4(+) cells, though they mature with significantly faster kinetics, reaching full maturation by 18 mo post-hHSCT. Between 4 and 6 y post-hHSCT, mature CD4(-) iNKT cells undergo a substantial expansion burst, resulting in a CD4(+)

Multicluster nosocomial outbreak of parainfluenza virus type 3 infection in a pediatric oncohematology unit: a phylogenetic study.

BACKGROUND: Human parainfluenza virus type 3 (hPIV-3) has been reported to cause nosocomial outbreaks of respiratory infection, in particular among hematopoietic stem cell transplantation recipients. DESIGN AND METHODS: From September 2007 through January 2008 several episodes of hPIV-3 infection were observed among young patients followed at the Oncohematology Unit (OHU) or other units of the Pediatrics Department. In 32 young patients (median age 3.5 years, range 21 days-27 years), hPIV-3 infection was diagnosed by direct fluorescent antibody staining of cells from respiratory secretions, and virus quantified by real-time RT-PCR in nasopharyngeal aspirates or bronchoalveolar lavage samples. In addition, the epidemiologic relatedness of hPIV-3 strains was investigated by sequencing two variable regions of the hemagglutinin-neuraminidase gene (nt 1-569 and nt 762-1239). RESULTS: Of the 32 hPIV-3-positive patients, 19 were hematopoietic stem cell transplantation recipients, 8 had hematologic malignancies, and 5 were immunocompetent children. Sixteen patients had upper, and 16 lower respiratory tract infection. All patients but one had high viral load in nasopharyngeal aspirates (>1.0x10(6) RNA copies/mL). One patient died from respiratory failure with a high viral load in bronchoalveolar lavage. Phylogenetic analysis showed that 16/32 strains were identical. Besides this major cluster, three other clusters were identified, each one defining a smaller outbreak. CONCLUSIONS: Phylogenetic analysis allows identification of the role of a single or multiple hPIV-3 strains in the person-to-person transmission within an outbreak occurring in clinical units.

Donor/recipient mixed chimerism does not predict graft failure in children with beta-thalassemia given an allogeneic cord blood transplant from an HLA-identical sibling.

BACKGROUND: Donor/recipient mixed chimerism has been reported to be associated with an increased risk of graft failure in patients with beta-thalassemia given a bone marrow transplant. We investigated the relationship between the degree of mixed chimerism over time and clinical outcome of children undergoing cord blood transplantation for beta-thalassemia. DESIGN AND METHODS: Twenty-seven consecutive children given a cord blood transplant from a related donor were analyzed by short tandem repeat polymerase chain reaction and their chimerism results were compared with those of 79 consecutive patients who received a bone marrow transplant from either a relative (RD-BMT, n=42) or an unrelated donor (UD-BMT, n=37). Cord blood and bone marrow recipients received comparable preparative regimens. RESULTS: All cord blood recipients engrafted and displayed mixed chimerism early after transplantation; 13/27 converted to full donor chimerism over time, while 14 maintained stable mixed chimerism; all patients are alive and transfusion-independent. Twenty-four of the 79 bone marrow-recipients (12 UD- and 12 RD-BMT) exhibited full donor chimerism at all time points examined, 4/79 (2 UD- and 2 RD-BMT) did not engraft and 51/79 (23 UD- and 28 RD-BMT) displayed mixed chimerism at the time of hematologic reconstitution. Forty of 51 bone marrow recipients with mixed chimerism converted to full donor chimerism (17 UD- and 23 RD-BMT), 3/51 maintained stable mixed chimerism (1 UD- and 2 RD-BMT), while 8/51 (5 UD- and 3 RD-BMT) progressively lost the graft, and became transfusion-dependent again. CONCLUSIONS: Mixed chimerism is a frequent event and does not predict the occurrence of graft failure in children with beta-thalassemia given a cord blood transplant from a relative.

Efficacy and safety of intrathecal liposomal cytarabine for the treatment of meningeal relapse in acute lymphoblastic leukemia: experience of two pediatric institutions.

The treatment of meningeal relapse in acute lymphoblastic leukemia (ALL) remains a challenging clinical problem. Liposomal cytarabine (DepoCyte) permits to decrease frequency of lumbar punctures, without loss of efficacy, because intrathecal levels of the drug remain cytotoxic for up to 14 days. We investigated the efficacy and safety of intrathecal DepoCyte in six children with meningeal relapse, treated in two pediatric institutions. DepoCyte was well tolerated in all patients, who achieved complete clearance of blasts from the cerebrospinal fluid after the first three intrathecal drug administrations. Five of the six patients were concurrently treated with high-dose administration of systemic cytarabine, without additional neurological side effects. Our results suggest that DepoCyte is a valid option for children with ALL experiencing meningeal relapse; it deserves further investigation in intensive treatment regimens, taking into due consideration potential neurotoxicity.

The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia.

The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30.2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (-14-bp/-14-bp vs +14-bp/+14-bp: Relative Risk = 15.0; 95% confidence interval 1.59-141.24; P = 0.008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation.

Adult height in patients treated for isolated growth hormone deficiency: role of birth weight.

To evaluate the effect of growth hormone (GH) administration on adult height (AH) in two groups of isolated GH-deficient (IGHD) children born either small (birth weight below -2 SD) or appropriate (birth weight above -2 SD) for gestational age (GA). Out of 35 prepubertal IGHD children, 14 small for GA (SGA, group A) and 21 appropriate for GA (AGA, group B) were examined. All patients received continuous GH treatment at a median dose of 0.028 mg/kg/day (range 0.023-0.032) in group A and 0.024 (range 0.023-0.028) in group B. GH treatment was administered for a period of 67.0 months (range 42.37-96.05) in group A and 54.31 months (range 47.14-69.31) in group B. All children were measured using a Harpenden stadiometer every 6 months until they reached AH (growth velocity <1 cm/year). The patients underwent a retesting a few months after stopping GH therapy. A significant difference was found between group A and B as expected for birth weight SD, -2.70 (range -2.87 to -2.29) and -0.73 (range -1.30 to 0.14) respectively (p < 0.000001) and interestingly also for body mass index SDS (BMI SDS) at retesting, 0.08 (range 0.30 to -1.51) and 0.61 (range 0.73 to -1.10) respectively (p < 0.04). We observed no significant differences between groups A and B in height (expressed as the SDS for chronological age, height SDS) at diagnosis (p = 0.75), height SDS at start of puberty (p = 0.51), height SDS at retesting (p = 0.50), target height SDS (TH SDS) (p = 0.47), AH SDS (p = 0.92), corrected height SDS (height SDS - TH SDS) (p = 0.60), BMI SDS at diagnosis (p = 0.25), GH dosage (p = 0.34) and therapy duration (p = 0.52). GH treatment with a standard dose in short IGHD children leads to a normalization of AH without any significant difference between SGA and AGA patients.