Therapeutic plasma exchange in paediatric nephrology in Ireland.

BACKGROUND: Therapeutic plasma exchange (TPE) is utilised in the management of a limited number of paediatric renal conditions. Despite its widespread acceptance and advancements in the practice of apheresis, there remains a paucity of data pertaining to paediatrics. We present a large retrospective review of our cohort of paediatric patients undergoing TPE for renal indications, outlining their outcomes and complications. METHODS: A retrospective chart review was conducted for all patients (under 16 years) undergoing TPE for renal conditions between January 2002 and June 2019 in Ireland. Demographic and clinical data were extracted, with patients anonymised and stratified according to their pathology. RESULTS: A total of 58 patients were identified. A total of 1137 exchanges were performed using heparin sodium anticoagulation. The median age was 35.5 months (IQR 18-110 months). The leading indication was neurological involvement in Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS) (n = 29). Complications (minor or major) occurred in 65.5% (n = 38) of patients, with most experiencing minor complications 58.6% (n = 34). Asymptomatic hypocalcaemia was the most common complication in 43.1% (n = 25). CONCLUSIONS: Our experience of TPE, spanning 1137 exchanges, proved a safe, well-tolerated therapy. Most complications were minor, and with therapy conducted in specialised centres, there are very low levels of adverse events.

Vaccine hesitancy and reported non-vaccination in an Irish pediatric outpatient population.

Vaccine hesitancy is defined as a delay in acceptance, or refusal, of vaccines, despite availability. It is a complex and context specific phenomenon and identified as a global health priority. The "Parent Attitudes about Childhood Vaccines" (PACV) questionnaire is a validated tool for identifying vaccine hesitancy. Our aim was to use the PACV to assess vaccine hesitancy and its relationship with reported non-vaccination in an Irish population, for the first time. Our participants were parents or caregivers of children attending general pediatric clinics in a tertiary pediatric hospital in Dublin, Ireland, between September and December 2018. In total, 436 participants completed the questionnaire. 5.5% of our population reported non-vaccination. Human papilloma virus and measles, mumps, rubella vaccines were the most commonly cited vaccines of concern (11.5% and 6.7%, respectively), and autism spectrum disorder was the most commonly side effect of concern (4.3%). Mean PACV score was 26.9 (SD 19.1), with a significant difference between non-vaccinators and vaccinators (53.2 vs 25.3, p<0.001). Safety and efficacy concerns were the major contributor to non-vaccination. 14.4% of our population were vaccine-hesitant using the conventional cut-off score, which increased to 22% when using an optimal cut-off which maximized sensitivity and specificity. The accuracy of the PACV score to identify non-vaccination was good (area under the ROC curve = 0.827), and the optimal cut-off had a high negative predictive value (98.5%).Conclusion: PACV identified reported non-vaccination with high accuracy in our population. It may be useful to screen vaccine-hesitant parents who could benefit from interventions to improve uptake. What is Known: • Vaccine hesitancy is a leading threat to global health, with falls in vaccine uptake associated with disease outbreaks worldwide. • The Parent Attitudes about Childhood Vaccines (PACV) questionnaire is a validated measure of vaccine hesitancy and correlates with non-vaccination in many populations. What is New: • This large study in a pediatric outpatient clinic setting represents the first use of the PACV in a Western European population to assess vaccination hesitancy. • The PACV may be an effective way of screening a pediatric clinic population to identify vaccine-hesitant parents or caregivers for targeted vaccine promotion.

Clinical Relapses of Atypical HUS on Eculizumab: Clinical Gap for Monitoring and Individualised Therapy.

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A humanised anti-C5 monoclonal antibody (eculizumab) is available for the treatment of aHUS. We present the first description of atypical HUS in a child with a coexistent diagnosis of a POL-III leukodystrophy. On standard eculizumab dosing regime, there was evidence of ongoing C5 cleavage and clinical relapses when immunologically challenged. Eculizumab is an effective therapy for aHUS, but the recommended doses may not be adequate for all patients, highlighting the need for ongoing efforts to develop a strategy for monitoring of treatment efficacy and potential individualisation of therapy.

Symmetrical thalamic calcification: A trio whole exome sequencing negative series.

Symmetrical thalamic calcification or bilateral symmetrical thalamic gliosis presents at delivery with hypertonia, fixed flexion contractures and prominent bulbar signs, without preceding perinatal asphyxia. At post-mortem, there is evidence of bilateral symmetrical selective thalamic neuronal encrustation and gliosis. To date, 27 cases are published with no underlying diagnosis identified. Two affected children from singleton pregnancies were reported and therefore, a genetic cause proposed. No previous reports have performed genetic testing to confirm or reject this hypothesis. We report three additional cases of this rare condition, expanding the clinical and pathological phenotype. We performed trio whole exome sequencing, the first in this cohort of patients, and did not identify a pathogenic variant. As postulated in the original report, the likely underlying mechanism is antenatal hypoxia in the third trimester.

Case report: Benefits and challenges of long-term eculizumab in atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually. Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy. The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown. Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future.