A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Key stakeholders' perspectives on the development of an early dietary phosphate self-management strategy for children and young people with chronic kidney disease stages 1-3: A modified Delphi consensus process.

BACKGROUND: An early dietary phosphate intervention (EPI) can provide vital medical benefits supporting self-management of chronic kidney disease (CKD) in childhood. OBJECTIVE: To utilise expert consensus to provide early modelling for an EPI to guide clinical practice across a paediatric renal network. METHODS: Forty-eight statements across six domains were constructed following a systematic review and semi-structured interviews with children and young people (CYP), parents and healthcare professionals (HCP). A three-round online Delphi survey with parents and paediatric renal multi-disciplinary healthcare experts was undertaken. RESULTS: Twenty-one experts agreed on 56 statements over three Delphi rounds. Statements were accepted in all six domains: definition of an EPI (2), rationale (12), intended users (3), delivery (14) (when [1], where [3], who [2], how [8]), other considerations (16) and potential concerns (9). CONCLUSIONS: Consensus was reached on a definition and a set of guiding principles, providing some early modelling for implementation and future research on the development of an EPI strategy for CYP with CKD.

Successful ABO and HLA incompatible kidney transplantation in children in the UK.

BACKGROUND: There is increasing evidence of good short-term and medium-term outcomes of ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation with pre-transplant positive crossmatches in paediatric practice. However, there remain concerns regarding the higher risks of infective complications and antibody-mediated rejections. The aim of our study is to show longer-term follow-up on all ABOi and HLAi paediatric kidney transplant recipients (pKTR) in the UK. METHODS: Questionnaires specifying kidney transplant type, desensitisation requirement and kidney allograft function were sent to 13 paediatric nephrology centres that performed kidney transplantation in children and young people under 18 years of age who received an ABOi and/or HLAi transplant between 1 January 2006 and 31 December 2016. Patient and kidney allograft survival were compared between ABOi, HLAi and ABO/HLA compatible (ABOc/HLAc) groups. RESULTS: Among 711 living donor kidney transplants performed in the UK, 23 were ABOi and 6 were HLAi. Patient survival was 87%, 100% and 96% in ABOi, HLAi and ABOc/HLAc groups, respectively, at median follow-up of 6.8 (3.6-14.0) years post-transplant. Death-censored kidney allograft survival was 100% in all 3 groups at last follow-up. There were no cases of primary non-function in ABOi or HLAi groups, but 2% in the ABOc/HLAc group. There was one reported case of Epstein-Barr viral-induced post-transplant lymphoproliferative disorder. CONCLUSION: Longer term follow-up has shown that ABOi and HLAi kidney transplantation are feasible for pKTR where no compatible donors are available, and that minimising desensitisation should be achieved where possible. A higher resolution version of the Graphical abstract is available as Supplementary information.

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome.

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.

Predicting Individual Patient Platelet Demand in a Large Tertiary Care Hospital Using Machine Learning.

Introduction: An increasing shortage of donor blood is expected, considering the demographic change in Germany. Due to the short shelf life and varying daily fluctuations in consumption, the storage of platelet concentrates (PCs) becomes challenging. This emphasizes the need for reliable prediction of needed PCs for the blood bank inventories. Therefore, the objective of this study was to evaluate multimodal data from multiple source systems within a hospital to predict the number of platelet transfusions in 3 days on a per-patient level. Methods: Data were collected from 25,190 (42% female and 58% male) patients between 2017 and 2021. For each patient, the number of received PCs, platelet count blood tests, drugs causing thrombocytopenia, acute platelet diseases, procedures, age, gender, and the period of a patient's hospital stay were collected. Two models were trained on samples using a sliding window of 7 days as input and a day 3 target. The model predicts whether a patient will be transfused 3 days in the future. The model was trained with an excessive hyperparameter search using patient-level repeated 5-fold cross-validation to optimize the average macro F2-score. Results: The trained models were tested on 5,022 unique patients. The best-performing model has a specificity of 0.99, a sensitivity of 0.37, an area under the precision-recall curve score of 0.45, an MCC score of 0.43, and an F1-score of 0.43. However, the model does not generalize well for cases when the need for a platelet transfusion is recognized. Conclusion: A patient AI-based platelet forecast could improve logistics management and reduce blood product waste. In this study, we build the first model to predict patient individual platelet demand. To the best of our knowledge, we are the first to introduce this approach. Our model predicts the need for platelet units for 3 days in the future. While sensitivity underperforms, specificity performs reliably. The model may be of clinical use as a pretest for potential patients needing a platelet transfusion within the next 3 days. As sensitivity needs to be improved, further studies should introduce deep learning and wider patient characterization to the methodological multimodal, multisource data approach. Furthermore, a hospital-wide consumption of PCs could be derived from individual predictions.

The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers.

The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2- early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2- breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2- eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2- breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2- eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.

Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome.

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal.

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: -7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m2 ). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.

Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy.

BACKGROUND: Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN. METHODS: We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource-Rare Diseases Study. We examined copy number, rare, and common variants. RESULTS: Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) (P=3.29×10-8; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 (P=1.21×10-8; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure. CONCLUSIONS: We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases.

Developing Consensus-Based Outcome Domains for Trials in Children and Adolescents With CKD: An International Delphi Survey.

RATIONALE & OBJECTIVE: The inconsistency in outcomes reported and lack of patient-reported outcomes across trials in children with chronic kidney disease (CKD) limits shared decision making. As part of the Standardized Outcomes in Nephrology (SONG)-Kids initiative, we aimed to generate a consensus-based prioritized list of critically important outcomes to be reported in all trials in children with CKD. STUDY DESIGN: An online 2-round Delphi survey in English, French, and Hindi languages. SETTINGS & PARTICIPANTS: Patients (aged 8-21 years), caregivers/family, and health care professionals (HCPs) rated the importance of outcomes using a 9-point Likert scale (7-9 indicating critical importance) and completed a Best-Worst Scale. ANALYTICAL APPROACH: We assessed the absolute and relative importance of outcomes. Comments were analyzed thematically. RESULTS: 557 participants (72 [13%] patients, 132 [24%] caregivers, and 353 [63%] HCPs) from 48 countries completed round 1 and 312 (56%) participants (28 [40%] patients, 64 [46%] caregivers, and 220 [56%] HCPs) completed round 2. Five outcomes were common in the top 10 for each group: mortality, kidney function, life participation, blood pressure, and infection. Caregivers and HCPs rated cardiovascular disease higher than patients. Patients gave lower ratings to all outcomes compared with caregivers/HCPs except they rated life participation (round 2 mean difference, 0.1), academic performance (0.1), mobility (0.4), and ability to travel (0.4) higher than caregivers and rated ability to travel (0.4) higher than HCPs. We identified 3 themes: alleviating disease and treatment burden, focusing on the whole child, and resolving fluctuating and conflicting goals. LIMITATIONS: Most participants completed the survey in English. CONCLUSIONS: Mortality, life participation, kidney function, and blood pressure were consistently highly prioritized by patients, caregivers, and HCPs. Patients gave higher priority to some lifestyle-related outcomes compared with caregivers/HCPs. Establishing critically important outcomes for all trials in children with CKD may improve consistent reporting of survival, kidney health, and clinical and life impact outcomes that are meaningful for decision making.

Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients' preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer.

BACKGROUND: The objective of the IMPROVE study was patients' preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer. METHODS: In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients' preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL). RESULTS: 61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first-/second-line, Cap+Bev) and 54.1% and 52.9% (first-/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines. CONCLUSIONS: Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians' preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported. TRIAL REGISTRATION: EudraCT No: 2013-005329-22. Registered on 19 August 20.

Correction to: Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study.

In the article by Möst et al., entitled "Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study.

Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomised controlled study.

OBJECTIVES: The aim of the present study was the qualitative and quantitative evaluation of osseous graft consolidation using allogeneic bone blocks for vertical bone augmentation in an animal model. MATERIAL AND METHODS: Standardised allogeneic and autologous bone blocks were fixed on the frontal skull of 20 adult female pigs and covered with a resorbable collagen membrane. Animals were sacrificed after 2 and 6 months. Specimens were histologically and histomorphometrically analysed focusing on the amount of vital bone, residual bone substitute material and connective tissue. Furthermore, the amount of expression of bone matrix proteins (collagen type I and osteocalcin) and de novo vessel formation (von Willebrand factor) were quantified by immunohistochemistry. RESULTS: Significantly more allogeneic bone blocks failed for both evaluation time points (p < 0.05). Allogeneic blocks showed significantly less vital bone with more connective tissue formation compared to autologous bone blocks. Increased vessel formation could be detected for both evaluation time points in the contact area of autologous bone with local bone. The expression of collagen type I and osteocalcin was significantly lower in the allogeneic bone graft. CONCLUSIONS: Allogeneic cancellous bone blocks showed a significantly higher failure rate compared to autologous bone blocks. Allogeneic bone blocks seemed to negatively affect bone formation or negatively influence the host in the long term, and increased connective tissue formation and block loss should be anticipated. CLINICAL RELEVANCE: In order to maintain patient safety and treatment success clinicians should be persuaded to make a conscious choice of the applied biomaterials with regard to their components and structure.

Retrospective 3D analysis of bone regeneration after cystectomy of odontogenic cysts.

BACKGROUND/OBJECTIVE: In this retrospective study, we aimed to investigate a new 3D evaluation method for evaluating bone regeneration after cystectomy of odontogenic cysts. METHODS: The study included 26 patients who underwent cystectomies between 2012 and 2017 and had received either fillings or non-fillings with autologous iliac crest. Bony regeneration was analyzed using 3D imaging software and comparing identical regions of interest (ROIs) that were determined by exact overlays of the postoperative cone beam computer tomography (CBCT) or computer tomography (CT) images. Outcome measures, including volume changes according to the defect size and configuration, patient age, the entity and distribution of the cysts, were collected. RESULTS: Twenty-six patients (5 women and 21 men) had 30 defects, including nine keratocysts, seven radicular cysts and 14 dentigerous cysts. A total of 73% of the defects were in the mandible. The mean 3D follow-up time was 12 months. According to the 3D evaluation of bony regeneration, the defect size and configuration showed no significant differences between the groups (filled or non-filled with 15 defects per group). CONCLUSIONS: By establishing a standardized 3D method for evaluating bone regeneration, healing can be better monitored and evaluated.

Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination: Results of a randomized trial.

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

Defining a threshold for tacrolimus intra-patient variability associated with late acute cellular rejection in paediatric kidney transplant recipients.

BACKGROUND: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known. METHODS: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels < 4 µg/L (Tac < 4) and the concentration/weight-adjusted dose (C/D) ratio as a proxy marker of tacrolimus metaboliser status. RESULTS: LACR patients had higher CV (median, IQR 44%, 36-61% v. 24%, 19-35%, p < 0.0001) and higher MAD (33%, 25-48% v. 19%, 15-26%, p < 0.0001). The MAD was less affected by outlying tacrolimus results. Receiver operating curve analysis of the MAD resulted in a sensitivity of 76% and specificity of 76% at a threshold of 26% (AUC 0.85, p < 0.05). LACR patients had more Tac < 4 (50% v. 26%, p < 0.05). There was no difference in C/D suggesting that good IPV can be maintained in fast metabolisers. Patients with LACR had significantly increased creatinine at 12-month follow-up despite treatment (108 v. 5 umol/L increase from baseline) and four patients lost their allograft. CONCLUSIONS: Monitoring of tacrolimus IPV using the MAD may be a clinical marker for LACR. A threshold IPV of 26% can potentially be used as a therapeutic target pending further validation studies.

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome.

OBJECTIVE: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution. METHODS: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells. RESULTS: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1-4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups. CONCLUSIONS: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.

Simultaneous multi-slice MRI using cartesian and radial FLASH and regularized nonlinear inversion: SMS-NLINV.

PURPOSE: The development of a calibrationless parallel imaging method for accelerated simultaneous multi-slice (SMS) MRI based on Regularized Nonlinear Inversion (NLINV), evaluated using Cartesian and radial fast low-angle shot (FLASH). THEORY AND METHODS: NLINV is a parallel imaging method that jointly estimates image content and coil sensitivities using a Newton-type method with regularization. Here, NLINV is extended to SMS-NLINV for reconstruction and separation of all simultaneously acquired slices. The performance of the extended method is evaluated for different sampling schemes using phantom and in vivo experiments based on Cartesian and radial SMS-FLASH sequences. RESULTS: The basic algorithm was validated in Cartesian experiments by comparison with ESPIRiT. For Cartesian and radial sampling, improved results are demonstrated compared to single-slice experiments, and it is further shown that sampling schemes using complementary samples outperform schemes with the same samples in each partition. CONCLUSION: The extension of the NLINV algorithm for SMS data was implemented and successfully demonstrated in combination with a Cartesian and radial SMS-FLASH sequence. Magn Reson Med 79:2057-2066, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Glucose-6-Phosphate Dehydrogenase Deficiency Mimicking Atypical Hemolytic Uremic Syndrome.

A 4-year-old boy presented with nonimmune hemolysis, thrombocytopenia, and acute kidney injury. Investigations for an underlying cause failed to identify a definitive cause and a putative diagnosis of complement-mediated atypical hemolytic uremic syndrome (aHUS) was made. The patient was started initially on plasma exchange and subsequently eculizumab therapy, after which his kidney function rapidly improved. While on eculizumab therapy, despite adequate complement blockade, he presented 2 more times with hemolytic anemia and thrombocytopenia, but without renal involvement. Genetic analysis did not uncover a mutation in any known aHUS gene (CFH, CFI, CFB, C3, CD46, THBD, INF2, and DGKE) and anti-factor H antibodies were undetectable. Whole-exome sequencing was undertaken to identify a cause for the eculizumab resistance. This revealed a pathogenic variant in G6PD (glucose-6-phosphate dehydrogenase), which was confirmed by functional analysis demonstrating decreased erythrocyte G6PD activity. Eculizumab therapy was withdrawn. Complement-mediated aHUS is a diagnosis of exclusion and this case highlights the diagnostic difficulty that remains without an immediately available biomarker for confirmation. This case of G6PD deficiency presented with a phenotype clinically indistinguishable from complement-mediated aHUS. We recommend that G6PD deficiency be included in the differential diagnosis of patients presenting with aHUS and suggest measuring erythrocyte G6PD concentrations in these patients.

Evaluation of Staff Satisfaction After Implementation of a Surgical Safety Checklist in the Ambulatory of an Oral and Maxillofacial Surgery Department and its Impact on Patient Safety.

PURPOSE: Safety checklists in medicine have been shown to be effective in the prevention of complications and adverse events in patients undergoing surgery. Such checklists are not as common in dentistry. The aims of this study were to propose a safety checklist for the ambulatory treatment of patients undergoing oral and implant surgery and to assess its impact on patient safety and staff satisfaction. MATERIALS AND METHODS: After implementation of a surgical safety checklist in the ambulatory treatment of patients undergoing oral and implant surgeries, a questionnaire regarding staff satisfaction and safety-related parameters was randomly administered. Incidents, complications, and adverse events were documented. Outcomes with (n = 40 surgeries) and without (n = 40 surgeries) use of the checklist were analyzed and compared. RESULTS: Staff reported high satisfaction with the use of the checklist, which demonstrably improved team communication and lowered stress levels during surgery. There was a statistically significantly higher frequency of reported incidents without the use of the checklist (n = 43) than with the use of the checklist (n = 10; P = .000). Most incidents were reported in the context of pre- and post-procedural processes. CONCLUSIONS: Safety checklists help to improve work processes, optimize communication, and lower stress levels. Their use in clinical dental practice is recommended.