Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies.

BACKGROUND: The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). PATIENTS AND METHODS: Following surgery, patients (0-36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. RESULTS: We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001-.019; d = 0.79-1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. CONCLUSION: Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae.

Decision Making in the Context of Paediatric Solid Organ Transplantation Medicine.

This manuscript aims to outline ethical, legal, and psychosocial key situations in the context of transplantation under special consideration of children. Besides being particularly vulnerable, children as minors by law are not meant to consent to whatever medical procedure is applied to them. Rather their next-of-kin and medical staff are to decide. In the context of transplantation thus it needs to be reflected under which circumstances a child can become an organ donor or receive an organ. This essay will not provide answers to current questions in transplantation medicine but provide an overview of present European practices and juxtapose divergent courses of action which are based on an assumed similar social-cultural background. Data are drawn from a systematic comparison of the various national organ transplantation laws and tissue acts. Ethical reflections are based on a thematically targeted literature search using PubMed Central and PhilPapers databases.

Adherence in pediatric renal recipients and its effect on graft outcome, a single-center, retrospective study.

BACKGROUND: In recent years, treatment-adherence gained increasing attention in nearly every area of medicine including transplant medicine. Medication adherence following solid organ transplantation is known to be indispensable for a satisfactory allograft survival. METHODS: We examined 60 patients between the ages of four months and 20 years who underwent kidney transplantation at Hannover Medical School between January 2011 and August 2017. Age at transplantation varied from 4 months to 20 years. 12 patients (20%) already underwent their second solid organ transplantation. 5 patients (8.3%) had a combined kidney-liver-transplantation. We used two different methods for rating adherence: An objective one based on the coefficient of variation (CoV%) of immunosuppressant trough levels, and a subjective questionnaire answered by the patients themselves, their parents or legal custodians, the treating pediatrician, as well as by the attending psychologist. RESULTS: The CoV% in our study was by-trend higher in those patients who suffered from a biopsy-proven rejection (x̅CoV% = 35.7, σ CoV% = 30.1 in patients with rejection vs. x̅ CoV% = 26.0, σ CoV% = 10.5 in patients without rejection). Furthermore, the psychologist's assessment correlated significantly both with rejections as well as with the formation of de novo donor-specific antibodies (dnDSA) while the pediatrician's rating showed no correlation (Prejections  = 0.005 and PdnDSA  = 0.03 for psychologist's rating vs. Prejections  = 0.50 and PdnDSA  = 0.50 for pediatrician). CONCLUSIONS: Apart from underlining the importance of medication adherence, the present research stresses the role of a multi-disciplinary treatment approach to support pediatric renal transplant recipients and their families.

Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome.

BACKGROUND: Acute kidney injury (AKI) is a major complication in children with hepatic failure which leads to increased morbidity and mortality. The aim of this study was to provide paediatric data on the prevalence of dialysis-dependent AKI (dAKI), the feasibility and efficacy of dialysis methods and outcome. METHODS: We conducted a retrospective analysis of 367 children listed for orthotopic liver transplantation (OLT) in our centre during the past decade. RESULTS: Data on 30 children (15 boys, 15 girls) were compiled for retrospective analysis, and data on dialysis feasibility and efficacy were available for 26 of these. Median age was 3.5 (range 0.4-17.7) years. Median MELD (Model For End-Stage Liver Disease) score was 33. dAKI was caused by hepato-renal syndrome in 16 of the 30 children. Twenty-one patients were treated with continuous veno-venous haemofiltration (CVVH), and nine patients received peritoneal dialysis (PD). Overall mortality was 77%. Mortality within the PD-group was 100 % versus 67% in the CVVH-group (p = 0.039). Urea reduction rate within the first 24 h of treatment was 12.9% in the PD group and 23.5% in the CVVH group (p = 0.019). CONCLUSIONS: Children with end-stage liver disease have a high risk for dAKI associated with high mortality. CVVH is associated with better efficacy and less mortality than PD.

A multimodal aftercare intervention improves the outcome after kidney transplantation - results of the KTx360° aftercare program using claims data.

Background: The after-care treatment project KTx360° aimed to reduce graft failure and mortality after kidney transplantation (KTx). Methods: The study was conducted in the study centers Hannover, Erlangen and Hannoversch Muenden from May 2017 to October 2020 under the trial registration ISRCTN29416382. The program provided a multimodal aftercare program including specialized case management, telemedicine support, psychological and exercise assessments, and interventions. For the analysis of graft failure, which was defined as death, re-transplantation or start of long-term dialysis, we used longitudinal claims data from participating statutory health insurances (SHI) which enabled us to compare participants with controls. To balance covariate distributions between these nonrandomized groups we used propensity score methodology, in particular the inverse probability of treatment weighting (IPTW) approach. Findings: In total, 930 adult participants were recruited at three different transplant centres in Germany, of whom 320 were incident (enrolled within the first year after KTx) and 610 prevalent (enrolled >1 year after KTx) patients. Due to differences in the availability of the claims data, the claims data of 411 participants and 418 controls could be used for the analyses. In the prevalent group we detected a significantly lower risk for graft failure in the study participants compared to the matched controls (HR = 0.13, 95% CI = 0.04-0.39, p = 0.005, n = 389 observations), whereas this difference could not be detected in the incident group (HR = 0.92, 95% CI = 0.54-1.56, p = 0.837, n = 440 observations). Interpretation: Our findings suggest that a multimodal and multidisciplinary aftercare intervention can significantly improve outcome after KTx, specifically in patients later after KTx. For evaluation of effects on these outcome parameters in patients enrolled within the first year after transplantation longer observation times are necessary. Funding: The study was funded by the Global Innovation fund of the Joint Federal Committee of the Federal Republic of Germany, grant number 01NVF16009.

Do We Need Palliative Care in Pediatric Nephrology? Patients' and Caregivers' Disease Experience.

Chronic life-limiting illnesses such as chronic kidney disease (CKD) require integral support to the families concerned in addition to medical care. Palliative care is an option to facilitate families to address future concerns, such as procedures for acute life-threatening complications, or to relieve physical and psychosocial suffering. The exact needs of patients or parents have not yet been investigated. To assess needs in supportive palliative care, we conducted a monocentric qualitative interview study. We included patients 14 to 24 years old as well as parents of younger children (below 14 years) with CKD ≥ stage 3. In total, fifteen interviews were conducted. Data were analyzed with a deductive and descriptive approach using qualitative content analysis as described by Mayring. Sociodemographic data and basic information of disease were collected using questionnaires. In contrast to caregivers, adolescents and young adults do not express worries about their own mortality or reduced life expectancy. Rather, they report about their limitations to everyday life associated with the disease, especially in the areas of school and work. They wish to live a normal life. Caregivers are concerned about the future and the disease trajectory. They also describe difficulties in balancing the management of the disease with other responsibilities such as work and healthy siblings' needs. Patients and caregivers appear to need a chance to talk about their everyday struggles and disease-related fears and concerns. Talking about their concerns and needs may help deal with their emotions and facilitate acceptance of their situation characterized by a life-limiting disease. Our study confirms the need for psychosocial support in pediatric nephrology to address the needs of the affected families. This can be offered by pediatric palliative care teams.

Barriers to the Successful Health Care Transition of Patients with Kidney Disease: A Mixed-Methods Study on the Perspectives of Adult Nephrologists.

The transition from paediatric to adult-based health care is a challenging period bearing a high risk of medication nonadherence and transplant loss in adolescents and young adults after kidney transplantation. Successful transition asks for the cooperation of many, not least the adult physicians. Yet little is known about their thoughts and attitudes on the transition. We conducted a cross-sectional mixed-methods study, inviting all nephrologists registered with the German Society of Nephrology. A total of 119/1984 nephrologists answered an online survey, and 9 nephrologists participated in expert interviews on transition experiences and perceived barriers. Interviews were thematically analysed. Based on the results, 30 key statements were listed and returned to participants for a ranking of their relevance. The main themes extracted are (1) available resources, (2) patient-related factors, (3) qualification and (4) preparation of and cooperation with the paediatric setting. In conclusion, it became evident that successful transition faces multiple obstacles. At the least, it asks for time, staff, and money. Rigid structures in health care leave little room for addressing the specific needs of this small group of patients. Transition becomes a topic one wants to and is able to afford.

Current management of transition of young people affected by rare renal conditions in the ERKNet.

Transition in medical care is a high-risk period in adolescence and young adulthood. To date, data on transition policy, its application in practice, and transition procedures in patients with rare, hereditary kidney diseases in Europe is scarce. An online survey was developed and was distributed within the paediatric centres of the European Reference Network for Rare Kidney Diseases (ERKNet) aiming to assess the transition-relevant structures from the providers' perspectives. Its items were based on the consensus statement on transition published by the International Society of Nephrology (ISN) and the International Paediatric Nephrology Association (IPNA) in 2011. Forty-six paediatric experts based at 28/32 ERKNet university hospitals participated. Annually, a median number of 14 patients (1-80) are transferred to adult based care. One centre continued to care for paediatric kidney transplant recipients throughout their entire lifespan. Choosing this option terminated the survey and no further data was obtained from this centre. 29/45 experts confirmed the application of an-at least unwritten-transition procedure (64%). Transition clinics are offered by 23 experts. Most physicians (40%) transfer patients at age 18-19, 10 experts at age <18. Most physicians transfer the patients to a university hospital and/or a community hospital. The transition guidelines have been implemented in ERKNet centres only partly and with huge heterogeneity. Implementation of transition tools and structures within ERKNet could improve health of children with hereditary kidney diseases. Adherence of experts to the transition-guidelines was significantly correlated with gross national income of their countries.

Survey on Management of Transition and Transfer From Pediatric- to Adult-based Care in Pediatric Kidney Transplant Recipients in Europe.

BACKGROUND: Transition from pediatric- to adult-based healthcare is a challenging period and bears a high risk of medication nonadherence and transplant loss in adolescents and young adults after kidney transplantation. Yet, it remains unclear how the 2011 International Society of Nephrology (ISN)/International Pediatric Nephrology Association (IPNA) guidelines on transition are implemented in practice and which healthcare transition modalities are currently used in Europe. METHODS: We performed an online survey inviting all members of the European Society of Paediatric Nephrology mailing list to participate. Adherence to ISN/IPNA guidelines was scored with a maximum of 15 points. RESULTS: Thirty-nine centers from 24 countries accounting for approximately 2500 children after kidney transplantation participated in the survey. At 3 centers, patients remained under pediatric care for their whole life, and 5 centers did not use any transition procedure. From the remaining 31 centers, 82% confirmed the existence of at least 1 unwritten transition procedure. None of these centers used IT or social media for patient training in transition. Specialized transition clinics are held at 15 of 31 centers for the patients. Most patients were transferred at 16 to 21 years of age. Transfer age was subject to regulation at 20 of 36 centers. Median score of guidelines adherence was 10 (range, 0-14). The adherence score was significantly correlated with gross national income (r2 = 0.631, P < 0.0001). CONCLUSIONS: The 2011 ISN/IPNA guidelines on transition are implemented insufficiently in European pediatric nephrology centers. Therefore, further development is needed, and the use of information technology and social media should be promoted.

Transition structures and timing of transfer from paediatric to adult-based care after kidney transplantation in Germany: a qualitative study.

OBJECTIVES: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents' lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process. SETTING: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed. RESULTS: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition. CONCLUSIONS: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge. TRIAL REGISTRATION NUMBER: ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).

Transitional Care and Adherence of Adolescents and Young Adults After Kidney Transplantation in Germany and Austria: A Binational Observatory Census Within the TRANSNephro Trial.

Transition from child to adult-oriented care is widely regarded a challenging period for young people with kidney transplants and is associated with a high risk of graft failure. We analyzed the existing transition structures in Germany and Austria using a questionnaire and retrospective data of 119 patients transferred in 2011 to 2012. Most centers (73%) confirmed agreements on the transition procedure. Patients' age at transfer was subject to regulation in 73% (18 years). Median age at transition was 18.3 years (16.5-36.7). Median serum creatinine increased from 123 to 132 µmol/L over the 12 month observation period before transfer (P = 0.002). A total of 25/119 patients showed increased creatinine ≥ 20% just before transfer. Biopsy proven rejection was found in 10/119 patients. Three patients lost their graft due to chronic graft nephropathy.Mean coefficient of variation (CoV%) of immunosuppression levels was 0.20 ± 0.1. Increased creatinine levels ≥ 20% just before transfer were less frequently seen in patients with CoV < 0.20 (P = 0.007). The majority of pediatric nephrology centers have internal agreements on transitional care. More than half of the patients had CoV of immunosuppression trough levels consistent with good adherence. Although, 20% of the patients showed increase in serum creatinine close to transfer.

The TRANSNephro-study examining a new transition model for post-kidney transplant adolescents and an analysis of the present health care: study protocol for a randomized controlled trial.

BACKGROUND: The transition from pediatric to nephrology care is not yet a standardized procedure. The result is an increased risk of deteriorating transplant function, with the potential for premature transplant failure. METHODS/DESIGN: In phase I of this study, we shall evaluate the current patient transition situation in all existing German pediatric and nephrology departments (n = 17), including an evaluation of the views of physicians, nurses, and psychosocial support staff regarding transition. Phase II will be a prospective, randomized study in which we compare current unstructured transition (control group) to structured transition (intervention group). The structured transition approach integrates the core elements of the Berliner TransitionsProgramm in combination with two facilitating smartphone apps. The primary endpoint of this study will be therapy adherence, as reflected by group variation coefficients of immunosuppressive agent levels. As a secondary outcome, we will compare patients' self-reported quality of life, satisfaction of patients and their parents with each transition model, and how patient-centered healthcare components are utilized. These secondary parameters will be assessed with established instruments or with instruments developed (and pilot tested) in phase I of the project. DISCUSSION: The long-term goal of this work is to provide a model of structured transition from pediatric to adult care for adolescent nephrology patients, in order to improve transplant survival and patient wellbeing. TRIAL REGISTRATION: Identifier: Clinicaltrials.gov: ISRCTN22988897, registered on 24 April 2014).