Strengthening paediatric competencies and educational skills among general paediatricians.

AIM: To develop a coherent programme that addresses the need for continuing professional development in general paediatrics and educational skills for senior paediatricians at outpatient clinics in Sweden today. METHODS: Educational needs in the target group were investigated using a questionnaire. Themes and sub-themes extracted from responses informed the curriculum formulation of the continuing professional development (CPD) programme, which was completed using a variety of learning, assessment and evaluation methods. RESULTS: Forty-six paediatricians identified 355 clinical situations. Competencies in general paediatrics and educational skills were incorporated in a CPD programme, implemented in western Sweden between 13 October 2016 and 23 May 2019, with 23 learning modules and 18 participants (male/female 3/15, median age 55 years). The participants' evaluation emphasised the importance of adult learning principles. Their responses to open reflective questions on 23 May 2109 suggested that the programme offered a learning environment in which they could develop their paediatric and educational practices and improve their mentorship, networks and work-based learning environment. They also described an enhanced feeling of joy at work. CONCLUSION: The involvement of experienced paediatricians in the programme formulation may be inspirational to clinicians and contribute to the definition, revitalisation and prioritisation of general paediatrics in Sweden in the future.

Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study.

BACKGROUND: Extrahepatic portal vein obstruction can have severe health consequences. Variceal bleeding associated with this disorder causes upper gastrointestinal bleeding, leading to substantial morbidity and mortality. We report the clinical transplantation of a deceased donor iliac vein graft repopulated with recipient autologous stem cells in a patient with extrahepatic portal vein obstruction. METHODS: A 10 year old girl with extrahepatic portal vein obstruction was admitted to the Sahlgrenska University Hospital in Gothenburg, Sweden, for a bypass procedure between the superior mesenteric vein and the intrahepatic left portal vein (meso Rex bypass). A 9 cm segment of allogeneic donor iliac vein was decellularised and subsequently recellularised with endothelial and smooth muscle cells differentiated from stem cells obtained from the bone marrow of the recipient. This graft was used because the patient's umbilical vein was not suitable and other strategies (eg, liver transplantation) require lifelong immunosuppression. FINDINGS: The graft immediately provided the recipient with a functional blood supply (25-30 cm/s in the portal vein and 40 mL/s in the artery was measured intraoperatively and confirmed with ultrasound). The patient had normal laboratory values for 9 months. However, at 1 year the blood flow was low and, on exploration, the shunt was patent but too narrow due to mechanical obstruction of tissue in the mesocolon. Once the tissue causing the compression was removed the graft dilated. We therefore used a second stem-cell populated vein graft to lengthen the previous graft. After this second operation, the portal pressure was reduced from 20 mm Hg to 13 mm Hg and blood flow was 25-40 cm/s in the portal vein. With restored portal circulation the patient has substantially improved physical and mental function and growth. The patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs. INTERPRETATION: An acellularised deceased donor vein graft recellularised with autologous stem cells can be considered for patients in need of vascular vein shunts without the need for immunosuppression. FUNDING: Swedish Government.

Stable long-term renal function after pediatric liver transplantation.

Long-term exposure to calcineurin inhibitors increases the risk of CKD in children after LT. The aims of this study were to study renal function by measuring GFRm before and yearly after LT, to describe the prevalence of CKD (stage III: GFR 30-60 mL/min/1.73 m(2)) and to investigate if age and underlying liver disease had an impact on long-term renal function. Thirty-six patients with a median age of 2.9 years (0.1-16 yr) were studied. Median follow-up was 6.5 (2-14 yr). GFRm decreased significantly during the first six months post-transplantation with 23% (p < 0.001). Thereafter renal function stabilized. At six months, 17% (n = 5) of the children presented CKD stage III and at five yr the prevalence of CKD III was 18% in 29 children. However, in 13 children with a 10-year follow-up it was 0%. None of the children required renal replacement therapy after LT. When analyzing renal function of those children younger than two yr (n = 14) and older than two yr (n = 17) at the time of transplantation, we found that in both cohorts the filtration rate remained remarkably stable during the five-yr observational period. However, there was a statistically significant (p < 0.05) difference in the percentual decrease in GFRm between the groups during the first six months after LT 13% and 31%, respectively. Baseline GFRm according to diagnosis did not differ between the groups. During the first six months after LT, patients transplanted for hepatic malignancy (n = 6) and those with metabolic liver disease (n = 4) had a percentage loss of GFRm of 32% and 35%, respectively. The corresponding loss of GFRm in patients with other diseases was 10-19%. Six months post-transplantation mean GFRm in the group with malignant liver disease was 65 +/- 15 mL/min/1.73 m(2) and in the group with other diseases (n = 24) 82 +/- 17 mL/min/1.73 m(2) (p < 0.05). At one, three and five yr post-transplantation there was no longer a statistically significant difference between these cohorts. Our findings suggest that there can be a long-term recovery of renal function after LT in children.

High Frequency of Concomitant Food Allergy Development and Autoantibody Formation in Children Who Have Undergone Liver Transplantation.

BACKGROUND: Allergy and other immune-mediated diseases are more frequently reported in children who have undergone liver transplantation. Furthermore, autoantibodies are also prevalent, suggesting a state of immune dysregulation in these patients. Whether or not these processes occur simultaneously in the same individual has not been studied previously. METHODS: A cohort of 43 children who had undergone liver transplantation for nonautoimmune liver disease at median age of 1.3 years was investigated for allergy and autoimmune disease. Sensitization to food and inhalant allergens was assessed, and autoantibodies were measured. RESULTS: The prevalence of food allergy was 26% and that of respiratory allergy was 23%, whereas 33% and 26% of the subjects were sensitized to food and inhalant allergens, respectively. Autoimmune disease (ie, autoimmune hepatitis) occurred in a single individual (2%), whereas autoantibodies were present in 44% of the children. Food allergy and autoantibodies occurred concomitantly in 19% of the children, which was almost twice the frequency expected by chance (11%, P = 0.04). Respiratory allergy and the presence of autoantibodies were unrelated (12% concurrence versus the expected 10%, P = 0.73). In the logistic regression analysis, autoantibody formation was associated with discontinued immunosuppression and food allergy, with odds ratios of 13 (P = 0.01) and 7.1 (P = 0.03), respectively. CONCLUSIONS: In contrast to respiratory allergy, food allergy and autoantibody formation occurred together in the same children who underwent liver transplantation at a frequency higher than would be expected by chance. This may reflect an underlying immune dysregulation that impairs immune tolerance to both food allergens and autoantigens.

Long-standing oral mucosal lesions in solid organ-transplanted children-a novel clinical entity.

BACKGROUND: Acute oral angioedema is well documented in young pediatric liver-transplanted patients. This is a report of an identified novel entity of long-standing oral mucosal lesions (OML) in children who had undergone solid organ transplantation. METHODS: In conjunction with routine medical follow-ups, all solid organ-transplanted children were examined annually for OML. RESULTS: Eight children developed a novel entity of long-standing OML after solid organ transplantation. Seven of the eight children had undergone liver transplantation whereas one child was kidney transplanted. The children received tacrolimus immunosuppression after transplantation. All recipients presented with multiple spherical nodules on the dorsum of the tongue, which later on displayed a fissured appearance. Most patients also presented with mucosal tags or ridges and swollen lips similar to those found in patients with orofacial granulomatosis. In addition, most patients had a clinical history of immediate-onset food-induced allergic reactions, including transient angioedema, after transplantation, but this clinical manifestation appeared separately from the long-standing lesions. CONCLUSION: A novel entity of long-standing OML that share some features with orofacial granulomatosis has been identified in children after solid organ transplantation.

Epstein-Barr viremia levels after pediatric liver transplantation as measured by real-time polymerase chain reaction.

Effective immunosuppression has improved the results following liver transplantation, but also increased the risk for opportunistic infections. Epstein-Barr virus (EBV) infection in transplant patients can cause various symptoms including the life-threatening premalignant condition, post-transplantation lymphoproliferative disorder (PTLD). Serum specimens from 24 consecutive children (mean 7.6 specimens/patient), who had undergone liver transplantation in Göteborg from January 1995 to May 2002, were analyzed retrospectively for EBV DNA by real-time TaqMan polymerase chain reaction (PCR). The results were related to clinical picture, immunosuppression, graft rejection and infections with other agents. Eleven patients (46%) developed primary EBV infection at a mean time of 4.8 months after transplantation, and six (25%) reactivated EBV infection at a mean of 4.0 months after transplantation. Four of the 11 patients with primary infection had symptomatic EBV infection: two had PTLD and two hepatitis. One patient in the group with reactivated infection developed PTLD. EBV DNA levels were significantly higher in the group with primary symptomatic infection compared with the patients with primary asymptomatic infection (mean 65 500 copies/mL; range 14 200-194 300 vs. 3700 copies/mL; range 100-9780). In patients with symptomatic infection EBV DNA levels did not differ between PTLD and hepatitis patients. The data suggest that quantitative analysis of EBV DNA in serum by real-time PCR is useful for identification of EBV-related disease.

Quantitative analysis of CMV DNA in children the first year after liver transplantation.

CMV infection is a major problem after solid organ transplantation especially in children where primary infection is more common than in adults. Early diagnosis is critical and might be facilitated by quantitative analysis of CMV DNA in blood. In this retrospective study of 18 children who had a liver transplantation 1995-2000, serum samples were analysed by Cobas Amplicor Monitor (Roche). Four patients developed symptomatic CMV infection at a mean time of 4 wk after transplantation. They showed maximum CMV DNA levels in serum of 26 400, 1900, 1300 and 970 copies/mL, respectively. In comparison, CA Monitor was positive, at a low level (415 copies/mL), in one of 11 patients with asymptomatic (4) or latent (7) infection. CMV IgM was detected at significant levels (> or =1/80) in all four patients with symptomatic, and in one with asymptomatic CMV infection. Eight patients were given one or several courses of ganciclovir. Five of these lacked symptoms of CMV disease, and had low (415 copies/mL) or undetectable CMV DNA in serum. The data suggest that quantitative analysis of CMV DNA may be of value in early identification of CMV disease and for avoiding unnecessary antiviral treatment.