Regulatory T cells (Treg) are a subpopulation of CD4+ T cells crucial for the establishment of immune homeostasis, due to their capacity to suppress the effector function of a wide range of cells. These Treg cells have become an intriguing field of study in autoimmunity, allergy and transplantation. However, current approaches for the manufacturing of Tregs from peripheral blood in adults have shown several limitations, due to the low frequency of Treg in periphery and the limited survival and suppressive phenotype in differentiated/memory Tregs. To resolve this drawback, we have explored the use of the thymic tissue, which is routinely discarded during pediatric cardiac surgeries, as an alternative source of Tregs to be employed as cell therapy. Firstly, we observed that the child had higher Treg counts and frequency in periphery than the adult subject, and most of the Treg from the child had a naïve phenotype. However, due to the limited blood volume that can be extracted from a child the quantity of Treg that can be purified from a child is much lower. As an alternative, we developed a GMP-compatible protocol to purify Treg from pediatric thymuses, obtaining massive amounts of thymus-derived Treg (thyTreg) with >90% purity and >90% survival. While the maximum quantity of Treg purified from peripheral blood in infants younger than 2 years old is <0.5 × 106 cells, we can obtain approximately 10000-fold more Treg from their thymic tissue. In conclusion, the massive quantity of thyTreg obtained from thymus along with their high purity suppressive capacity and survival, could overcome the drawbacks of employing Treg from peripheral blood. ThyTreg constitutes a therapeutic arsenal with infinite possibilities for the treatment of immune-related diseases, including autoimmune disorders or immune graft rejection. At present, we are initiating a “first-in-human” clinical trial to explore the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent graft rejection in heart-transplanted children.

Severe disease caused by Clostridium difficile is frequently encountered in transplant recipients and carries a high mortality. Numerous studies have been published on this subject in the adult population, but few in the pediatric setting. A 4-year-old boy who had undergone heart transplant 20 months earlier was admitted to the pediatric intensive care unit after humoral rejection. Seven days after admission, he developed septic shock, abdominal distension, and paralytic ileus without diarrhea. Pseudomembranous colitis due to C. difficile was confirmed by microbiological and radiological studies. Despite treatment with rectal vancomycin and intravenous metronidazole, the patient did not improve and required decompressive laparotomy; because of the poor subsequent clinical course, terminal ileostomy and cecostomy were performed in a second operation. Recovery was satisfactory, and surgical reconstruction of intestinal tract was performed 3 months later without complications. Although early surgery with total colectomy is indicated, when there is a poor response to medical treatment in cases of C. difficile toxic megacolon, the case we present responded favorably to a conservative surgical approach that enabled intestinal integrity to be restored 3 months later. In the pediatric population, less aggressive therapeutic options should be considered, as they have benefits on the subsequent quality of life of the patient.

ABSTRACT Background: Nutrition is important in childhood because the child has a lower energy reserve than the adult and a higher demand for calories because of ongoing growth. In this study, the utility of transpyloric enteral feeding (TEF) in critically ill children was evaluated. Methods: A prospective, descriptive study was made in a pediatric intensive care unit of a tertiary pediatric center of 41 critically ill children, 30 after surgical procedures and 11 with nonsurgical illness, aged 8 days to 12 years, who received transpyloric enteral feeding with 8‐ or 10‐Fr weighted feeding tubes. Analysis was made of tolerance and complications (vomiting, abdominal distension, excessive gastric residual, diarrhea, and pulmonary aspiration) of TEF. Results: The mean duration of TEF was 19.5 ± 26.8 days (range, 1‐120 days). The administration of sedative agents or inotropic drugs did not alter toleration of TEF. Eight of 12 patients treated with continuous infusion of vecuronium tolerated TEF without complications. Eleven gastrointestinal complications occurred in 10 patients, abdominal distension and excessive gastric residual in 7 (17%), and diarrhea in 4 (9.7%). In 7 patients gastrointestinal complications improved, with decreasing use or transitory interruption of TEF, but in 4 patients (9.7%), TEF had to be withdrawn. Gastrointestinal complications were more frequent in postsurgical than in nonsurgical patients ( p < 0.001). No patients suffered from pulmonary aspiration, and the incidence of pulmonary infection and hepatic dysfunction diminished during TEF. Conclusions: Transpyloric enteral feeding is a good method of nutritional support in critically ill children and can be used in patients treated with neuromuscular blocking agents. The frequency and severity of complications and the risks of pulmonary infection and hepatic dysfunction related to TEF are low.