Successful emergency renal auto-transplantation in a child with renovascular disease.

Renal artery occlusion is a rare but potentially catastrophic complication of paediatric endovascular renal artery intervention. Emergency auto-transplantation may be required to salvage the kidney; to date this has only been described in adults. We report our experience of performing emergency kidney auto-transplantation following acute renal artery thrombosis in a child undergoing redo renal artery angioplasty A 20-month-old boy presented with refractory hypertension and hypertensive cardiomyopathy secondary to multifocal fibromuscular dysplasia (FMD) with a single functioning kidney. Acute thrombosis of the renal artery during redo-endovascular balloon angioplasty necessitated emergency renal auto-transplantation. Subsequent acute kidney injury was reversible with benefit to renal function in the medium-term despite prolonged warm ischaemic time of two hours. We recommend that high-risk patients undergoing renal artery intervention do so at centres with on-site renal and vascular surgical backup.

Reliability of systolic blood pressure measured by parents in young children at home using a hand held doppler device and aneroid sphygmomanometer.

OBJECTIVE: We report data regarding systolic BP monitoring in children aged <5 years performed over a 2-week period by parents at home using a hand-held doppler device and aneroid sphygmomanometer for SBP measurements (HDBPM). Our objectives were to compare health professional measured office systolic BP by doppler device (Office-SBP Doppler ) with parent measured home systolic BP using the same doppler device (Home-SBP Doppler ). We also report data evaluating reliability and optimal number of days of measurement required. DESIGN AND METHODS: We taught parents to measure systolic BP and assessed their technique using a hand-held doppler device and aneroid sphygmomanometer. We requested parents to perform three consecutive BP measurements twice daily (ideally morning and evening around similar times) when the child was awake, settled and cooperative. RESULTS: Over a 3-year period, data from 48 of 62 children who underwent HDBPM measurements were evaluated with median (IQR) age of 1.9 (0.9, 3.6) years, 27 (56%) boys and 14 (29%) on antihypertensive medication. Office-SBP Doppler was 2.9 ±â€Š8.9 mmHg [95% confidence interval (CI), -14.4 to 20.4, P  = 0.026] higher than Home-SBP Doppler . Mean Home-SBP Doppler between Week-1 and Week-2 monitoring was similar -0.45 ±â€Š3.5 mmHg (95% CI, -7.35 to 6.45, P  = 0.41). Morning HDBPM measurements were lower than evening with a mean difference of -2.77 ±â€Š3.92 mmHg, P  < 0.001). Over Week-1, mean Home-SBP Doppler was closer to mean Office-SBP Doppler with increasing cumulative days of monitoring and with smaller standard deviations suggesting that readings become more reliable from day 4 onwards. CONCLUSIONS: HDBPM is a reliable method for measuring systolic BP in young children with BP levels measured by parents comparable to those performed by health professional in clinic. HDBPM technique described here and performed by parents over a 7-day period with a minimum of 4-days, offers a reliable and reproducible technique to measure blood pressure at home.

Utilizing 3D printing to facilitate surgical in-situ paediatric renal artery aneurysm repair for refractory hypertension.

Renal artery aneurysmal (RAA) disease is a rare, but potentially life-threatening cause of renovascular disease presenting with hypertension. Conventional management involves aneurysmal excision followed by renal auto-transplantation. We present the management of a 13-year-old girl with complex multiple saccular aneurysmal disease of the left renal artery with hilar extension and symptomatic hypertension. We used 3D printing to print a patient-specific model that was not implanted in the patient but was used for surgical planning and discussion with the patient and their family. Endovascular options were precluded due to anatomical complexities. Following multi-disciplinary review and patient-specific 3D printing, she underwent successful in-situ RAA repair with intraoperative cooling, without the need for auto-transplantation. 3D printing enabled appreciation of aneurysmal spatial configuration and dimensions that also helped plan the interposition graft length needed following aneurysmal excision. The models provided informed multidisciplinary communications and proved valuable during the consent process with the family for this high-risk procedure. To our knowledge, this is the first reported case utilizing 3D printing to facilitate in-situ complex repair of RAA with intra-hilar extension for paediatric renovascular disease.

Demographics of childhood hypertension in the UK: a report from the Southeast England.

We aimed to describe hypertensive phenotype and demographic characteristics in children and adolescents referred to our paediatric hypertension service. We compared age, ethnicity and BMI in primary hypertension (PH) compared to those with secondary hypertension (SH) and white coat hypertension (WCH). Demographic and anthropometric data were collected for children and adolescents up to age 18 referred to our service for evaluation of suspected hypertension over a 6 year period. Office blood pressure (BP) and out of office BP were performed. Patients were categorised as normotensive (normal office and out of office BP), WCH (abnormal office BP, normal out of office BP), PH (both office and out of office BP abnormal, no underlying cause identified) and SH (both office and out of office BP abnormal, with a secondary cause identified). 548 children and adolescents with mean ± SD age of 10.1 ± 5.8 years and 58.2% girls. Fifty seven percent (n = 314) were hypertensive; of these, 47 (15%), 84 (27%) and 183 (58%) had WCH, PH and SH, respectively. SH presented throughout childhood, whereas PH and WCH peaked in adolescence. Non-White ethnicity was more prevalent within those diagnosed with PH than both the background population and those diagnosed with SH. Higher BMI z-scores were observed in those with PH compared to SH. Hypertensive children <6 years are most likely to have SH and have negligible rates of WCH and PH. PH accounted for 27% of hypertension diagnoses in children and adolescents, with the highest prevalence in adolescence, those of non-White Ethnicity and with excess weight.

Measurement of SBP at home by parents using hand-held Doppler device and aneroid sphygmomanometer: a single-centre experience.

OBJECTIVE: We taught parents to use at home a hand-held Doppler device and aneroid sphygmomanometer for SBPmeasurement (HDBPM). METHODS: Retrospective study including all children referred to evaluate hypertension over a 6-year period. Each child underwent HDBPM measurements performed by parents while awake over 2 weeks with three measurements performed twice daily. RESULTS: Of n = 155 children, 145 (93.5%) were successful and aged median (interquartile range) 2.48 (1.01, 5.12) years, including 85 boys. Overall, there were 25, 19, 30 and 26% aged less than 1, 1 to less than 2, 2 to less than 5 and at least 5 years old, respectively. Seventy-eight (54%) had been referred for confirming diagnosis and 67 (46%) for ongoing monitoring of treated hypertension. Following HDBPM, 70 of 78 (90%) patients in the 'Diagnosis subgroup' were observed to have normal blood pressure (BP). In the monitoring subgroup, treated hypertension that required no medication changes was recorded in 35 of 67 (52%) and medication changed in 32 of 67 (48%), [increased, decreased or changed] in 22, 6 and 5%, respectively. In 10 of 67 (15%) medication was weaned and stopped completely following HDBPM. None of the children required admission to hospital to evaluate their BP level or manage hypertension. CONCLUSION: Out-of-office BP monitoring using HDBPM is acceptable to children and families of young children when parents are taught to measure BP and supported by health professionals. We report evidence of the feasibility and clinical utility of HDBPM in a challenging population of children who are either too young or unable to tolerate 24-h ambulatory BP monitoring for both the diagnosis and ongoing management of clinically relevant hypertension.

Comparable on-therapy mortality and supportive care requirements in Black and White patients following initial induction for pediatric acute myeloid leukemia.

BACKGROUND: Black patients with acute myeloid leukemia (AML) are more likely to present with high acuity and consequently experience higher rates of induction mortality than white patients. Given the consistently identified racial disparities in overall survival (OS) among patients with AML, we aimed to evaluate whether there were sustained on-therapy racial differences in inpatient mortality, intensive care unit (ICU) requirements, or supportive care beyond initial induction. PROCEDURE: Within a retrospective cohort of 1239 children diagnosed with AML between 2004 and 2014 in the Pediatric Health Information System (PHIS) database who survived their initial course of induction chemotherapy, we compared on-therapy inpatient mortality, ICU-level care requirements, treatment course duration, cumulative length of hospital stay (LOS), and resource utilization after induction I by race. RESULTS: Over the period from the start of induction II through completion of frontline chemotherapy, there were no significant differences in mortality (adjusted odds ratios [OR], 1.01; 95% confidence intervals [CI], 0.41-2.48), ICU-level care requirements (adjusted OR, 0.93; 95% CI, 0.69-1.26), LOS (adjusted mean difference, 3.2 days; 95% CI, -2.3-9.6), or supportive care resource utilization for black patients relative to white patients. Course-specific analyses also demonstrated no differences by race. CONCLUSION: Although black patients have higher acuity at presentation and higher induction mortality, such disparities do not persist over subsequent frontline chemotherapy treatment. This finding allows interventions aimed at reducing disparities to be directed at presentation and induction.

Engineering the unicellular alga Phaeodactylum tricornutum for high-value plant triterpenoid production.

Plant triterpenoids constitute a diverse class of organic compounds that play a major role in development, plant defence and environmental interaction. Several triterpenes have demonstrated potential as pharmaceuticals. One example is betulin, which has shown promise as a pharmaceutical precursor for the treatment of certain cancers and HIV. Major challenges for triterpenoid commercialization include their low production levels and their cost-effective purification from the complex mixtures present in their natural hosts. Therefore, attempts to produce these compounds in industrially relevant microbial systems such as bacteria and yeasts have attracted great interest. Here, we report the production of the triterpenes betulin and its precursor lupeol in the photosynthetic diatom Phaeodactylum tricornutum, a unicellular eukaryotic alga. This was achieved by introducing three plant enzymes in the microalga: a Lotus japonicus oxidosqualene cyclase and a Medicago truncatula cytochrome P450 along with its native reductase. The introduction of the L. japonicus oxidosqualene cyclase perturbed the mRNA expression levels of the native mevalonate and sterol biosynthesis pathway. The best performing strains were selected and grown in a 550-L pilot-scale photobioreactor facility. To our knowledge, this is the most extensive pathway engineering undertaken in a diatom and the first time that a sapogenin has been artificially produced in a microalga, demonstrating the feasibility of the photo-bio-production of more complex high-value, metabolites in microalgae.

Early blood stream infection following allogeneic hematopoietic stem cell transplantation is a risk factor for acute grade III-IV GVHD in children and adolescents.

BACKGROUND: Graft-versus-host disease (GVHD) remains a major cause of mortality and morbidity in allogeneic hematopoietic stem cell transplantation (HSCT). In adults, early blood stream infection (BSI) and acute GVHD (AGVHD) have been reported to be related. The impact of BSI on risk for AGVHD, however, has not been assessed in pediatric patients. PROCEDURE: We conducted a retrospective analysis to test the hypothesis that early BSI (before day +30) predisposes allogeneic pediatric transplant patients to severe AGVHD. We analyzed 293 allogeneic HSCT performed at Children's Healthcare of Atlanta between 2005 and 2014 that met eligibility criteria. RESULTS: The cumulative incidence of acute grade III-IV GVHD at 100 days after HSCT was 17.1%. In multivariate analysis, risk for acute grade III-IV GVHD was associated with HLA-mismatched donor (hazard ratio [HR] = 4.870, P < 0.001), and BSI between day 0 and +30 prior to AGVHD (HR = 3.010, P = 0.001). CONCLUSIONS: These results indicate that early BSI appears to be a risk factor for acute grade III-IV GVHD. Further research is needed to determine if the link is causal.

CD36-positive B-lymphoblasts Predict Poor Outcome in Children With B-lymphoblastic Leukemia.

Objective We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36+ B-LL compared to patients with CD36- B-LL. Methods We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts. CD36- control patients were chosen from our leukemia database and matched 2:1 to CD36+ patients for National Cancer Institute (NCI) risk group at diagnosis. We reviewed diagnostic marrow slides for cytoplasmic granules and abstracted clinical data from patient charts. To identify underlying genetic abnormalities, clinical FISH testing and RNA sequencing was performed on 5 of our CD36+ patients, and RNA-seq data from the NIH Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL Expansion Phase 2 data set were examined. Results Twenty-five of 366 (6.83%) patients diagnosed at our institution in the study period had CD36+ blasts. With a median follow-up of 5.32 years, 5-year event-free survival (EFS) and overall survival (OS) were significantly worse for CD36+ patients compared to CD36- patients who were NCI Standard Risk at diagnosis (EFS: 60% ± 15.49 vs 95% ± 4.87, P = .016; OS: 90% ± 9.5 vs 100%, P = .019). NCI Standard Risk patients whose blasts were both CD36+ and had granules had the worst survival compared to CD36- patients without granules (EFS 25% ± 21.65 vs 95% ± 4.87, P = .0004). From our CD36+ patients and the TARGET database, we found 2 ABL2 mutations, 1 PDGFRB mutation, and 2 NRAS mutations. Conclusions For NCI Standard Risk patients, CD36 expression on B-lymphoblasts identifies patients with B-LL who have especially poor outcome. This may be due to underlying genetic abnormalities that may be amenable to targeted therapy.

A mixed-methods study exploring sign-off mentorship practices in relation to the Nursing and Midwifery Council standards.

AIMS AND OBJECTIVES: To investigate the current practice and experience of sign-off mentors in one NHS trust. BACKGROUND: In the UK, sign-off mentors support nursing students in their last clinical placement and are accountable for the final assessment of fitness to practice as a registered nurse. DESIGN: Mixed-methods study. METHODS: The focus was on two key Nursing and Midwifery Council standards: the requirement for students to work at least 40% of their time on clinical placement with a sign-off mentor/mentor; the sign-off mentor had one-hour-per-week protected time to meet the final placement student. Data were collected through two audits of clinical and university documents and an experience survey administered to all sign-off mentors in one trust. RESULTS: The audits showed that only 22/42 (52%) of students were supervised by their sign-off mentor/mentor at least 40% of the time, whilst 10/42 (24%) students never worked a shift with their sign-off mentor. Only one student met their sign-off mentor every week. Complete data were available in 31/64 (47%) sign-off mentors, of whom 21/30 (70%) rarely/never had reduced clinical commitment to mentor final placement students. Furthermore, 19/28 (68%) met their student after their shift had ended with 24/30 (80%) reporting not getting any protected time. CONCLUSION: Sign-off mentors have inadequate time and resources to undertake their role, yet are accountable for confirming the student has the required knowledge and skills to practise safely. The current model needs urgent review to improve mentoring standards. RELEVANCE TO CLINICAL PRACTICE: Understanding how the role of the sign-off mentor is working in practice is critical to ensuring that the Nursing and Midwifery Council standards are met, ensuring students are well supported and appropriately assessed in practice, and mentoring is given the high profile it deserves to guarantee high-quality care and protecting the public.