The Ponseti Method for the Treatment of Clubfeet Associated With Down Syndrome: A Single-institution 18-year Experience.

BACKGROUND: Although the Ponseti method has been used with great success in a variety of nonidiopathic clubfoot deformities, the efficacy of this treatment in clubfeet associated with Down syndrome remains unreported. The purpose of this study is, therefore, to compare treatment characteristics and outcomes of clubfoot patients with Down syndrome to those with idiopathic clubfoot treated with the Ponseti method. METHODS: An Institutional Review Board-approved, retrospective review of prospectively gathered data were performed at a single pediatric hospital over an 18-year period. Patients with either idiopathic clubfeet or clubfeet associated with Down syndrome who were less than 1 year of age at the outset of treatment were treated by the Ponseti method, and had a minimum of 2 year's follow-up were included. Initial Dimeglio score, number of casts, need for heel cord tenotomy, recurrence, and need for further surgery were recorded. Outcomes were classified using the Richards classification system: "good" (plantigrade foot +/- heel cord tenotomy), "fair" (need for a limited procedure), or "poor" (need for a full posteromedial release). RESULTS: Twenty clubfeet in 13 patients with Down syndrome and 320 idiopathic clubfeet in 215 patients were identified. Average follow-up was 73 months for the Down syndrome cohort and 62 months for the idiopathic cohort. Down syndrome patients presented for treatment at a significantly older age (61 vs. 16 d, P =0.00) and with significantly lower average initial Dimeglio scores than the idiopathic cohort (11.3 vs. 13.4, P =0.02). Heel cord tenotomy was performed in 80% of the Down syndrome cohort and 79% of the idiopathic cohort ( P =1.00). Recurrence rates were higher in the Down syndrome cohort (60%) compared with the idiopathic group (37%), but this difference was not statistically significant ( P =0.06). Need for later surgical procedures was similar between the 2 cohorts, though recurrences in the Down syndrome group were significantly less likely to require intra-articular surgery (8.3% vs. 65.5%, P =0.00). Clinical outcomes were 95% "good," 0% "fair," and 5% "poor" in the Down syndrome cohort and 69% "good," 27% "fair," and 4% "poor" in the idiopathic cohort ( P =0.01). CONCLUSIONS: Despite the milder deformity and an older age at presentation, clubfeet associated with Down syndrome have similar rates of recurrence and may have better clinical outcomes when compared with their idiopathic counterparts. When deformities do relapse in Down syndrome patients, significantly less intra-articular surgery is required than for idiopathic clubfeet. LEVEL OF EVIDENCE: Level III.

Latex allergy guidelines for people with spina bifida.

An estimated 85% of individuals with spina bifida (SB) survive into adulthood, warranting SB-specific transition to adult healthcare guidelines to address the diverse and complex medical, adaptive, and social needs particular to this condition. Latex allergy constitutes one important health concern for this population that requires ongoing and life-long evidence-based management. This article discusses management of latex allergy according to the SB Latex Allergy Healthcare Guidelines from the 2018 Spina Bifida Association's Fourth Edition of the Guidelines for the Care of People with Spina Bifida, reviews current care models in which such latex allergy guidelines can be implemented, and explores further relevant research topics in SB care relative to latex allergy.

Identification of an Sp factor-dependent promoter in GCET, a gene expressed at high levels in germinal center B cells.

Antigen-stimulated B lymphocytes undergo genetic and phenotypic changes in germinal centers (GCs), including affinity maturation of immunoglobulin (Ig) genes and Ig heavy chain isotype switching. Expression of the Germinal Center Expressed Transcript (GCET) gene is up-regulated in murine GC B cells. The human homolog of GCET, HGAL/GCET2, is an important prognostic marker for staging lymphomas derived from GCs. To identify mechanisms that control cell type-specific transcription of GCET, we localized promoter sequences using S1 nuclease protection and functional assays. Sequences comprising a TATA-less promoter were localized to a short region upstream of multiple mRNA start sites. In functional assays, the promoter is active in cells irrespectively of endogenous GCET gene expression. In vitro binding assays identified a non-consensus binding site for Sp factors near sites of transcriptional initiation. The site binds Spl and Sp3 in nuclear extracts and recombinant Spl in vitro, and is required for full promoter function in transient promoter assays. Activation of the promoter by Spl or Sp3 in Spl/3-deficient cells was largely dependent on the Sp site. Together, these data provide the first analysis of regulatory modules necessary for GCET expression, a model for GC B cell-specific transcription.

Requirements for selective recruitment of Ets proteins and activation of mb-1/Ig-alpha gene transcription by Pax-5 (BSAP).

Pax-5, a member of the paired domain family of transcription factors, is a key regulator of B lymphocyte-specific transcription and differentiation. A major target of Pax-5-mediated activation is the mb-1 gene, which encodes the essential transmembrane signaling protein Ig-alpha. Pax-5 recruits three members of the Ets family of transcription factors: Ets-1, Fli-1 and GABPalpha (with GABPbeta1), to assemble ternary complexes on the mb-1 promoter in vitro. Using the Pax-5:Ets-1:DNA crystal structure as a guide, we defined amino acid requirements for transcriptional activation of endogenous mb-1 genes using a novel cell-based assay. Mutations in the beta-hairpin/beta-turn of the DNA-binding domain of Pax-5 demonstrated its importance for DNA sequence recognition and activation of mb-1 transcription. Mutations of amino acids contacting Ets-1 in the crystal structure reduced or blocked mb-1 promoter activation. One of these mutations, Q22A, resulted in greatly reduced mb-1 gene transcript levels, concurrent with the loss of its ability to recruit Fli-1 to bind the promoter in vitro. In contrast, the mutation had no effect on recruitment of the related Ets protein GABPalpha (with GABPbeta1). These data further define requirements for Pax-5 function in vivo and reveal the complexity of interactions required for cooperative partnerships between transcription factors.