Diagnostic and treatment preferences for developmental dysplasia of the hip: a survey of EPOS and POSNA members.

PURPOSE: The aim of this study was to elucidate developmental dysplasia of the hip (DDH) diagnosis and treatment preferences among members of the Pediatric Orthopaedic Society of North America (POSNA) and European Paediatric Orthopaedic Society (EPOS). METHODS: A 54-question survey on DDH diagnosis and treatment preferences was distributed to POSNA and EPOS members. Descriptive statistics were performed. RESULTS: A total of 459 responses were analyzed. Ultrasound was the preferred modality for diagnosing DDH in infants less than six months old; few surgeons preferred radiographs. In all, 57% of POSNA members had radiology technicians perform ultrasounds, only 7% of EPOS members did. The percent coverage defining a dislocated hip varied greatly, the most frequent response being < 20% for POSNA and < 40% for EPOS members. Pavlik harnesses were the most popular harness/brace, used by 90% of POSNA and 71% of EPOS members. POSNA members were more likely than EPOS members to use a rigid abduction brace following initial harness/brace failure. For residual acetabular dysplasia, POSNA members were twice as likely as EPOS members to institute hip abduction bracing. Most surgeons would not perform closed reduction at less than three months of age or open reduction at less than six months of age. Most EPOS -members used traction prior to reduction; few POSNA members did. Few POSNA and EPOS members believed that reduction should be delayed until the ossific nucleus was visible. CONCLUSION: There is great variation in the preferred methods for diagnosing and treating DDH. This survey is the largest transcontinental survey to compile diagnostic and treatment preferences for DDH. With wide variations in practice, there is room for quality improvement.

Coexistence of meconium ileus with duodenal atresia and trisomy 21 in a newborn: a case report.

The coexistence of duodenal atresia (DA) may mask the antenatal ultrasound findings of meconium ileus (MI) and delay its postnatal diagnosis. We report a rare case of MI in a newborn infant diagnosed antenatally to have trisomy 21 and DA. The diagnosis of MI was only established intraoperatively after the patient showed persistent signs of intestinal obstruction following the surgical repair of the DA.

Liraglutide, a long-acting human glucagon-like peptide 1 analog, improves glucose homeostasis in marginal mass islet transplantation in mice.

The current scarcity of high-quality deceased pancreas donors prevents widespread application of islet transplantation for treatment of labile type 1 diabetes mellitus. Opportunities for the improvement of current techniques include optimization of islet isolation and purification, use of culture with pharmacological insulinotropic agents, strategies to reduce graft rejection and inflammation, and the search for alternative insulin producing tissue. Here, we report our findings on the efficacy of the long-acting human glucagon-like peptide 1 analog, liraglutide, in a mouse model of marginal mass islet transplantation. Liraglutide was administered (200 microg/kg sc twice daily) after a marginal mass syngeneic islet transplant in streptozotocin-induced diabetic BALB/c mice. Time-to-normoglycemia was significantly shorter in liraglutide-treated animals (median 1 vs. 7 d; P = 0.0003), even in recipients receiving sirolimus (median 1 vs. 72.5 d; P < 0.0001). Liraglutide-treated animals also demonstrated improved glucose tolerance as assessed by an ip glucose tolerance test. Liraglutide discontinuation at postoperative d 90 resulted in diminished glucose tolerance during the ip glucose tolerance test, whereas a late-start liraglutide therapy 90 d after transplant resulted in no improvement. These findings suggest that liraglutide therapy mediates early and late insulinotropic effects. In accord with this hypothesis, insulin/terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling fluorescence microscopy showed reduced transplanted beta-cell apoptosis in liraglutide-treated recipients 48 h after transplant. In addition, liraglutide resulted in improved glucose-dependent insulin secretion. Overall, our data show that liraglutide has a beneficial impact on the engraftment and function of syngeneic islet transplants in mice, when administered continuously starting on the day of transplant.

Combined coinhibitory and costimulatory modulation with anti-BTLA and CTLA4Ig facilitates tolerance in murine islet allografts.

Complex interactions between positive and negative cosignaling receptors ultimately determine the fate of the immune response. The recently identified coinhibitory receptor, B and T lymphocyte attenuator (BTLA), contributes to regulation of autoimmune and potentially alloimmune responses. We investigated the role of BTLA in a fully major histocompatibility complex-mismatched mouse islet transplant model. We report that anti-BTLA mAb (6F7) alone does not accelerate graft rejection. Rather, while CTLA4Ig alone improved allograft survival, the addition of anti-BTLA mAb to CTLA4Ig led to indefinite (>100 days) allograft survival. Immediately after treatment with anti-BTLA mAb and CTLA4Ig, islet allografts showed intact islets and insulin production despite a host cellular response, with local accumulation of Foxp3+ cells. We clearly demonstrate that combined therapy with anti-BTLA mAb and CTLA4Ig mice induced donor-specific tolerance, since mice accepted a second donor-specific islet graft without further treatment and rejected third party grafts. CTLA4Ig and anti-BTLA mAb limited the initial in vivo proliferation of CFSE-labeled allogeneic lymphocytes, and anti-BTLA mAb enhanced the proportion of PD-1 expressing T cells while depleting pathogenic BTLA+ lymphocytes. We conclude that targeting the BTLA pathway in conjunction with CTLA4Ig costimulatory blockade may be a useful strategy for promoting immunological tolerance in murine islet allografts.

Human islet function is not impaired by the sphingosine-1-phosphate receptor modulator FTY720.

Clinical islet transplantation for type 1 diabetes mellitus currently requires potent immunosuppressive drugs, which limits the procedure to the most severe forms of the disease, and many of the drugs are directly beta-cell toxic. A class of compounds called sphingosine-1-phosphate receptor modulators has been explored in transplantation and shown to be highly effective in multiple sclerosis and other autoimmune conditions. While FTY720, the first drug in this class, may not move forward initially in transplantation, this class requires detailed investigation to assess direct impact upon human beta-cell function and survival. We set out to evaluate the effects of FTY720 on human islets in vitro by investigating glucose-stimulated insulin and apoptosis; and in vivo, after transplantation into immunodeficient mice with chemically induced diabetes, by examining blood glucose levels, oral glucose tolerance tests and stimulated human C-peptide over a 50-day follow-up period. Our data showed that neither in vitro, nor in vivo human islet function was impaired by FTY720 exposure. Since FTY720 demonstrated no detrimental effects on human islet function in vitro or in vivo, emerging S1PR modulators may prove to be useful adjuncts in clinical islet transplantation through lack of diabetogenicity and potent immunological protection.