Report of the CCFA pediatric bone, growth and muscle health workshop, New York City, November 11-12, 2011, with updates.

Growth retardation, delayed puberty, decreased bone mass, altered bone architecture, hypovitaminosis D and skeletal muscle mass deficits are common in children with inflammatory bowel diseases. The Crohn's and Colitis Foundation of America sponsored a multidisciplinary workshop on the subject of Bone and Skeletal Growth in Pediatric IBD, held in New York City in November 2011. The topic of the workshop was a key recommendation of the Foundation's Pediatric Challenges meeting in 2005.

Shoulder arthroscopy in children and adolescents.

Arthroscopy is increasingly being used to manage a wide range of pathologies in the pediatric population. Knee arthroscopy is an efficacious treatment method for skeletally immature patients, and an increasing number of shoulder conditions can be managed with minimally invasive techniques. Special considerations are needed with regard to anatomy, anesthetic technique, equipment, and patient positioning when performing shoulder arthroscopy in a child or an adolescent.

Chronic high Epstein-Barr viral load carriage in pediatric small bowel transplant recipients.

The development of EBV infection and PTLD is normally associated with a high EBV load in peripheral blood. Often, children undergoing primary or reactivation of EBV infection subsequent to ITx will have chronically elevated EBV loads. To better understand this phenomenon and its consequences, we retrospectively reviewed the records of children who underwent ITx (either isolated or part of multivisceral transplantation) at our center from 1992 to 2007, to identify chronic high EBV load carriers in this population.

A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity.

ZAP-70 is critical for T cell receptor (TCR) signaling. Tyrosine to phenylalanine mutations of Y315 and Y319 in ZAP-70 suggest these residues function to recruit downstream effector molecules, but mutagenesis and crystallization studies reveal that these residues also play an important role in autoinhibition ZAP-70. To address the importance of the scaffolding function, we generated a zap70 mutant mouse (YYAA mouse) with Y315 and Y319 both mutated to alanines.

Characterization of regulatory T cells in urban newborns.

Background: In the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers.

A non-leaky Artemis-deficient mouse that accurately models the human severe combined immune deficiency phenotype, including resistance to hematopoietic stem cell transplantation.

Two Artemis-deficient (mArt(-/-)) mouse models, generated independently on 129/SvJ backgrounds, have the expected T(-)B(-)NK(+) severe combined immune deficiency (SCID) phenotype but fail to mimic the human disease because of CD4(+) T cell leakiness. Moreover, immune reconstitution after hematopoietic stem cell transplantation is achieved more readily in these leaky mouse models than in Artemis-deficient humans. To develop a more clinically relevant animal model, we backcrossed the mArt(-/-) mutation onto the C57Bl/6 (B6) background (99.

Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976: follow-up of a Children's Oncology Group cohort.

Background: The growing number of individuals surviving childhood cancer has increased the awareness of adverse long-term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs).

Methods: The authors describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors who were treated on legacy Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005.

Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation.

To determine whether T cell engraftment and recovery of B cell immunity could be improved, we prospectively treated 15 children with severe combined immunodeficiency disease (SCID) with megadoses of haplocompatible CD34(+) cells and a fixed number of CD3(+) cells without previous myeloablative chemotherapy. Evidence of T cell engraftment was seen in 73% of patients (95% confidence interval [CI] = 48%-90%). Engraftment was more likely in patients with X-linked SCID and in those with evidence of maternal engraftment at the time of diagnosis.

A novel missense RAG-1 mutation results in T-B-NK+ SCID in Athabascan-speaking Dine Indians from the Canadian Northwest Territories.

DNA double-strand repair factors in the non-homologous end joining (NHEJ) pathway resolve DNA double-strand breaks introduced by the recombination-activating gene (RAG) proteins during V(D)J recombination of T and B lymphocyte receptor genes. Defective NHEJ and subsequent failure of V(D)J recombination leads to severe combined immunodeficiency disease (SCID). We originally linked T(-)B(-)NK(+) SCID in Athabascan-speaking Native Americans in the Southwestern US and Northwest Territories of Canada to chromosome 10.

Neonatal mitral and tricuspid valve repair for in utero papillary muscle rupture.

Background: Papillary muscle rupture in the fetus and neonate is a rare event that leads to severe mitral or tricuspid insufficiency and is associated with high perinatal mortality. We undertook surgical repair of this lesion in the neonatal period and report on our midterm results.

Methods: Three neonates with tricuspid insufficiency and 1 infant with mitral insufficiency, all due to papillary muscle or chordal rupture, underwent surgical repair with artificial chordal replacement and a modification of the de Vega annuloplasty technique that allowed external adjustment of the annulus size under transesophageal echocardiographic guidance after separation from cardiopulmonary bypass.

Prone positioning can be safely performed in critically ill infants and children.

Objective: To describe the effects of prone positioning on airway management, mechanical ventilation, enteral nutrition, pain and sedation management, and staff utilization in infants and children with acute lung injury.

Design: Secondary analysis of data collected in a multiple-center, randomized, controlled clinical trial of supine vs. prone positioning.

B7.2-/- mature dendritic cells generate T-helper 2 and regulatory T donor cells in fetal mice after in utero allogeneic bone marrow transplantation.

In utero hematopoietic stem cell transplantation (IUT) results in limited chimerism and tolerance to alloantigens. We studied the relative role of B7.1 and B7.