Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

The Role of the Multiparametric MRI LiverMultiScanTM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis.

Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.

Feasibility and Acceptability of a mHealth Self-Management Intervention for Pediatric Transplant Families.

Families of pediatric solid organ transplant recipients need ongoing education and support in the first 30 days following hospital discharge for the transplantation. The purpose of this report is to describe the feasibility, acceptability, and preliminary efficacy of a mHealth family-self management intervention, (myFAMI), designed to improve post-discharge outcomes of coping, family quality of life, self-efficacy, family self-management, and utilization of health care resources. We enrolled 46 primary family members. myFAMI was feasible and acceptable; 81% (n=17/21) of family members completed the app at least 24/30 days (goal 80% completion rate). Family members generated 134 trigger alerts and received a nurse response within the goal timeframe of < 2 h 99% of the time. Although there were no significant differences between groups, primary outcomes were in the expected direction. The intervention was well received and is feasible for future post-discharge interventions for families of children who receive an organ transplant.

Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound.

Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy. Only five families with prenatal presentation of IPEX syndrome have been reported. Here, we present two additional prenatal onset cases with novel inherited frameshift pathogenic variants in FOXP3 that generate premature stop codons. Ultrasound findings in the first patient identified echogenic bowel, echogenic debris, scalp edema, and hydrops. In the second patient, ultrasound findings included polyhydramnios with echogenic debris, prominent fluid-filled loops of bowel, and echogenic bowel. These cases further broaden the phenotypic spectrum of IPEX syndrome by describing previously unappreciated prenatal ultrasound findings associated with the disease.

Vulnerability and chronic illness management in pediatric kidney and liver transplant recipients.

CONTEXT: Solid-organ transplant is the treatment of choice for end-stage organ failure and requires a transition from management of a life-threatening condition to a chronic illness. Despite research focusing on quality of life after transplant, there is a gap addressing the role of managing a chronic illness focusing on vulnerability and impact on family. OBJECTIVE: Identify patient and family patterns of adaptation among kidney and liver transplant recipients in regard to (1) vulnerability, (2) impact of illness on the family, (3) family functioning, and (4) quality of life (parent and child report). DESIGN: Cross-sectional study enrolling children 5 to 18 years old and their parent at a single time point after kidney or liver transplant. Validated self-report tools were completed. RESULTS: In all, 47 participants (24 kidney and 23 liver) were recruited. Mean age at transplant was 4.0 (kidney) and 2.1 (liver) years. Mean age at report was 12.1 (kidney) and 7.1 (liver) years. Child vulnerability correlated negatively with (1) family impact in the kidney (P < .05) and liver (P < .05) transplant groups, (2) PedsQL subscales including Parent Emotional (P< .05), Parent Social (P< .01), Parent Psychosocial (P < .01), Parent Physical (P < .05), Parent School (P < .05), and Child Social (P < .01) in the kidney transplant group, (3) PedsQL Parent Emotional subscale (P< .01) in the liver transplant group, and (4) Functional status (P < .01) in the liver transplant group. CONCLUSIONS: Child vulnerability provides insight into quality of life and the impact of illness on the family and family functioning.

Pediatric solid organ transplant recipients: transition to home and chronic illness care.

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post-discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care.

Transition from hospital to home following pediatric solid organ transplant: qualitative findings of parent experience.

Transplant providers are challenged to determine appropriate interventions for patients and families due to limited published research regarding the context of the post-discharge experience from the perspective of parents of transplanted children. The purpose of this study is to describe the parent perspective of the transition from hospital to home following their child's solid organ transplant. Within a mixed-methods design, 37 parents of pediatric heart, kidney, and liver transplant recipients from three pediatric hospitals responded to qualitative interview questions on the day of hospital discharge and three wk following hospital discharge. Insight to the discharge preparation process revealed necessary education components. Post-discharge themes were identified for coping, knowledge, and adherence. The parents' responses provide awareness as to specific stressors and concerns parents are faced with when their child is discharged from the hospital after solid organ transplant and opportunities for ways the transplant team can provide support.

What do large scale studies of medication in schizophrenia add to our management strategies?

INTRODUCTION: A number of large naturalistic trials have reported in recent years comparing second generation antipsychotic drugs with their predecessors. The conclusions they draw have rightly sparked much debate, but are these studies truly comparable? If not, which of them are most methodologically robust and are these the studies most suitable as a foundation for clinical care guidelines with a strong evidence base. We aimed to conduct a review of the current literature to establish the appropriateness of several recent major clinical studies being used as the basis for clinical guidelines. METHOD: A literature search using the PUBMED database was carried out. Five major studies comparing antipsychotic efficacy were selected as possible candidates and subjected to further analysis. The studies were: * CUTLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia study); * CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness study); * SOHO (Schizophrenia outpatients Health Outcomes study); * CAFE (Comparison of Atypicals in First Episode study); * EUFEST (European First Episode Schizophrenia Trial). DISCUSSION: The trials: * CAFE - the trial, although well randomised and blinded, uses discontinuation as a primary endpoint - this is hard to draw conclusions from: patients may discontinue due to side effects, due to lack of efficacy or with against medical advice for a multitude of reasons. As a secondary endpoint, the study does make use of a PANSS scoring system to measure efficacy, adding some weight to the conclusion that olanzapine, quetiaine and risperidone in early psychosis patients have equivalent efficacies. * CATIE - This trial was a comparative study, and so lacked a control arm and used discontinuation of medication an inverse measure of efficacy - an easily quantifiable event, but making for difficult interpretation. However most criticism has been directed at the unusually low (quitiapine, ziprasidone) and high (olanzapine and perphenazine) doses of drug used, which were reflected in their differing rates of efficacy. * CUtLASS This trial allows for less generalisation of its findings to the general population as it makes use a specific sub-population (those switching from one medication to another after a period of treatment). Also some patients were prescribed oral medications and some depot injections - making comparisons difficult due to possible differences in compliance. * EUFEST This trial makes use of discontinuation as an endpoint with the weaknesses we have described. Treatment of first episodes of psychosis is shown to be feasible, but it could not suggest if haloperidol or second generation drugs may be more efficacious. * SOHO - This trial hindered by the observational design of the study and small numbers reaching the primary end point (4%) caution should be exercised in the conclusion that olanzapine is superior to risperidone, quetiapine or typical antipsychotics. CONCLUSION: There is much information useful for clinical practice to be gathered from the results of these major studies, however, interpretation is hampered by both variations and weakness in study design. On balance it does appear that different antipsychotics possess differing efficacy, but also of relevance to the development of sound clinical guidelines is their differing side effects profile.