Rejection is one of the most important drawbacks for graft and patient survival in intestinal and multivisceral transplantation. However, there is no consensus on the diagnostic criteria for humoral rejection, and the literature about the role of donor-specific antibodies (DSA) on allograft outcome and the risk factors that contribute to their development is scant with contradictory results. The present study analyzes the role of DSA exclusively in a pediatric cohort of 43 transplants. Among our patients, 11.6% showed preformed DSA, but they did not correlate with more rejection or less allograft survival. Having previous transplants was the main sensitization factor with an odds ratio (OR) = 44.85 (P = 0.001). In total, 16.3% of recipients developed de novo donor-specific antibodies (dnDSA), mostly directed against human leukocyte antigen (HLA) class II, polyspecific and complement fixing. Additionally, the presence of dnDSA had a deleterious effect on graft rejection (hazard ratio [HR] = 11.00; P = 0.01) and survival (HR = 66.52; P < 0.001) in an observational period of 5 years after transplantation. The inclusion of the liver emerged as the main protective factor against dnDSA development with an OR = 0.07 (P = 0.007). The analysis of HLA compatibility at the serological and epitope level with the computational tools HLAMatchmaker and PIRCHE revealed no association between HLA mismatching and dnDSA. In conclusion, this study performed in pediatric recipients shows the deleterious effect of dnDSA on intestinal transplantation supported by the complement-fixing activity observed. Additionally, the liver inclusion in the allografts showed to be a protective factor against dnDSA generation.
Introduction Preoperative stress and anxiety in pediatric patients are associated with poor compliance during induction of anesthesia and a higher incidence of postoperative maladaptive behaviors. The aim of our study was to determine which preoperative preparation strategy improves compliance of the child during induction and decreases the incidence and intensity of emergence delirium (ED) in children undergoing ambulatory pediatric surgery.
Materials and Methods This prospective observational study included 638 pediatric American Society of Anesthesiologists I–II patients who underwent ambulatory pediatric surgery, grouped into four preoperative preparation groups: NADA (not premedicated), MDZ (premedicated with midazolam), PPIA (parental presence during induction of anesthesia), and PPIA + MDZ. The results were subsequently analyzed in four age subgroups: Group 1 (0–12 months), Group 2 (13–60 months), Group 3 (61–96 months), and Group 4 (> 96 months). Preoperative anxiety (modified Yale Preoperative Anxiety Scale [m-YPAS]), compliance of the child during induction (Induction Compliance Checklist [ICC]), and ED (Pediatric Anesthesia Emergence Delirium scale) were analyzed in each group.
Results Eighty-one percent of patients in the PPIA + MDZ preparation group presented a perfect compliance during the induction of anesthesia (ICC = 0), less preoperative anxiety (mean score m-YPAS = 26), less probability of ED (odds ratio: 10, 5 [3–37.5]; p < 0.05), and less ED intensity compared with the NADA group (1.2 vs. 5.8; p = 0.001).
Conclusion PPIA associated with midazolam premedication improves compliance during induction and decreases the incidence and intensity of ED.
Conclusions: GAL pretreatment constitutes a novel and promising therapy to reduce local and remote damage triggered by intestinal ischemiaereperfusion injury. Further in vivo and in vitro studies to understand GAL's modulatory effects are warranted.
The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.
To review our experience using sirolimus in a single centre paediatric intestinal transplantation cohort. Intestinal transplant patients with more than 3 months follow-up were divided into two groups according to their immunosuppression regimen: tacrolimus, (TAC group, n = 45 grafts) or sirolimus (SRL group, n = 38 grafts), which included those partially or completely converted from tacrolimus to sirolimus. The indications to switch were tacrolimus side effects and immunological complications. Survival and complications were retrospectively analysed comparing both groups. SRL was introduced 9 months (0 months-16.9 years) after transplant. The main cause for conversion was worsening renal function (45%), followed by haemolytic anaemia (21%) and graft-versus-host-disease (16%). Both groups showed a similar overall patient/graft survival (P = 0.76/0.08) and occurrence of rejection (24%/17%, P = 0.36). Immunological complications did not recur after conversion. Renal function significantly improved in most SRL patients. After a median follow-up of 65.17 months, 28/46 survivors were on SRL, 26 with monotherapy, with good graft function. Over one-third of our patients eventually required SRL conversion that allowed to improve their kidney function and immunological events, without entailing additional complications or survival impairment. Further trials are warranted to clarify the potential improvement of the standard tacrolimus maintenance by sirolimus conversion or addition.
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