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Background Hemoconcentration has been identified as a risk factor for a complicated course in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS). This single-center study assesses hemoconcentration and predictors at presentation in STEC-HUS treated from 2009-2017. Methods Data of 107 pediatric patients with STEC-HUS were analyzed retrospectively. Patients with mild HUS (mHUS, definition: max. serum creatinine < 1.5 mg/dL and no major neurological symptoms) were compared to patients with severe HUS (sHUS, definition: max. serum creatinine [greater than or equal to] 1.5 mg/dL ± major neurological symptoms). Additionally, predictors of complicated HUS (dialysis ± major neurological symptoms) were analyzed. Results Sixteen of one hundred seven (15%) patients had mHUS. Admission of patients with sHUS occurred median 2 days earlier after the onset of symptoms than in patients with mHUS. On admission, patients with subsequent sHUS had significantly higher median hemoglobin (9.5 g/dL (3.6-15.7) vs. 8.5 g/dL (4.2-11.5), p = 0.016) than patients with mHUS. The product of hemoglobin (g/dL) and LDH (U/L) (cutoff value 13,302, sensitivity 78.0%, specificity of 87.5%) was a predictor of severe vs. mild HUS. Creatinine (AUC 0.86, 95% CI 0.79-0.93) and the previously published score hemoglobin (g/dL) + 2 x creatinine (mg/dL) showed a good prediction for development of complicated HUS (AUC 0.87, 95% CI 0.80-0.93). Conclusions At presentation, patients with subsequent severe STEC-HUS had a higher degree of hemoconcentration. This underlines that fluid loss or reduced fluid intake/administration may be a risk factor for severe HUS. The good predictive value of the score hemoglobin (g/dL) + 2 x creatinine (mg/dL) for complicated HUS could be validated in our cohort. Graphical abstract, Author(s): Sebastian Loos [sup.1] , Jun Oh [sup.1] [sup.2] , Laura van de Loo [sup.1] , Markus J. Kemper [sup.3] , Martin Blohm [sup.1] , Raphael Schild [sup.1] Author Affiliations: [...]

Background Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening microangiopathy, frequently causing kidney failure. Inhibition of the terminal complement complex with eculizumab is the only licensed treatment but mostly requires long-term administration and risks severe side effects. The underlying genetic cause of aHUS is thought to influence the severity of initial and recurring episodes, with milder courses in patients with mutations in membrane cofactor protein (MCP). Methods Twenty pediatric cases of aHUS due to isolated heterozygous MCP mutations were reported from 12 German pediatric nephrology centers to describe initial presentation, timing of relapses, treatment, and kidney outcome. Results The median age of onset was 4.6 years, with a female to male ratio of 1:3. Without eculizumab maintenance therapy, 50% (9/18) of the patients experienced a first relapse after a median period of 3.8 years. Kaplan-Meier analysis showed a relapse-free survival of 93% at 1 year. Four patients received eculizumab long-term treatment, while 3 patients received short courses. We could not show a benefit from complement blockade therapy on long term kidney function, independent of short-term or long-term treatment. To prevent 1 relapse with eculizumab, the theoretical number-needed-to-treat (NNT) was 15 for the first year and 3 for the first 5 years after initial presentation. Conclusion Our study shows that heterozygous MCP mutations cause aHUS with a risk of first relapse of about 10% per year, resulting in large NNTs for prevention of relapses with eculizumab. More studies are needed to define an optimal treatment schedule for patients with MCP mutations to minimize the risks of the disease and treatment., Author(s): Verena Klämbt [sup.1] , Charlotte Gimpel [sup.2] , Martin Bald [sup.3] , Christopher Gerken [sup.4] , Heiko Billing [sup.5] , Sebastian Loos [sup.6] , Matthias Hansen [sup.7] , Jens [...]

Hemolytic uremic syndrome caused by Shiga toxin-producing E. coli (STEC-HUS) is often associated with a severe morbidity including neurological involvement and a mortality of 1-5%. Although STEC-HUS is often self-limited, improvement of treatment strategies is needed for cases with complications and, among others, plasma exchange/plasmapheresis and use of antibiotics have been advocated. With the availability of the complement blocker eculizumab, now a standard treatment of atypical HUS, several series have addressed its use in STEC-HUS, with variable response; randomized controlled trials are lacking. In this issue of Pediatric Nephrology, Pecheron et al. present a cohort of 33 pediatric patients with severe HUS treated with eculizumab. Neurological involvement was observed in 85% of the patients and 94% required dialysis. Most patients (55%) did not benefit from eculizumab and renal dysfunction as well as neurological sequelae did not resolve. In a subgroup of patients, however, rapid neurological improvement was described. In the post-hoc-defined group of patients with favorable outcome, there was a trend towards more sustained complement inhibition, although this finding was not significant compared to patients with an unfavorable outcome. Because multiple interventions were used and the study did not include any control group, future controlled studies are urgently needed to resolve the debate as to whether eculizumab can be an effective treatment for both prevention and treatment of complications in STEC-HUS., Author(s): Sebastian Loos [sup.1] , Jun Oh [sup.1] , Markus J. Kemper [sup.2] Author Affiliations: (Aff1) 0000 0001 2180 3484, grid.13648.38, University Children's Hospital, University Medical Center Hamburg-Eppendorf, , Hamburg, [...]

The presence of renal oligohydramnios (ROH) in a fetus has been associated in the past with a poor prognosis for survival, although recent studies have shown that survival has improved considerably due to the advances in neonatology and pediatric nephrology. In an article recently published in Pediatric Nephrology, evaluation of a large series by Mehler and colleagues confirms the improved prognosis, showing a survival rate of 32 of 38 (84%). In addition, only 12 of 35 (34%) neonates required renal replacement therapy. In five of these 12 children the dialysis could be terminated after the neonatal period. This study has important implications on the decision-making process and counseling of families. While 37% of families of the study opted for termination of pregnancies, palliative care was chosen by 8% of the families, representing an important option when a decision cannot be made rapidly by affected families. A multidisciplinary approach is not only necessary in the active treatment of neonates with a history of ROH but also in antenatal counseling. In this regard future efforts should establish consensus on an ethical framework for the decision-making process in ROH., Author(s): Sebastian Loos [sup.1] , Markus J. Kemper [sup.2] Author Affiliations: (Aff1) 0000 0001 2180 3484, grid.13648.38, University Children's Hospital, University Medical Center Hamburg-Eppendorf, , Hamburg, Germany (Aff2) Department of [...]

Background The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. Methods Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. Results Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). Conclusions Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months. Keywords Hemolytic uremic syndrome * E. coli 0104:H4 * Children * Neurology * Outcome, Introduction Hemolytic uremic syndrome (HUS) is defined by the triad of hemolytic anemia, thrombocytopenia and acute kidney injury [1]. It is the most common cause of acute kidney injury during [...]

Background B-cells are increasingly recognized as important players in alloimmunity. B cell-activating factor (BAFF) and its receptor BAFF-R are essential for B-cell differentiation and survival. Data on BAFF levels in pediatric renal transplant (RT) patients are scarce. Objective It is known from adult data that elevated BAFF levels correlate with an unfavorable outcome in bone marrow and kidney recipients. To analyze this hypothesis in pediatric renal transplant patients we performed a cross-sectional analysis of serum BAFF levels, lymphocyte surface BAFF-R expression, and clinical variables in a cohort of 43 pediatric renal transplant patients. Methods We studied serum BAFF, CD19+ B-, and FoxP3+ regulatory T-cells (Tregs) and BAFF-R expression in 43 children 2.9 (0.1-12.4) years after RT on maintenance immunosuppression. Twenty-two healthy children and 19 children with chronic kidney disease stage 5 (CKD5) served as controls. Results BAFF levels were significantly higher in RT patients than in healthy children (1,435 ± 574 vs 894 ± 189 pg/mL; p < 0.0001) whereas numbers of B-cells and Tregs were significantly lower. BAFF-R expression on B-cells was decreased after RT (531 ± 334 vs 707 [+ or -] 257 MFI; p < 0.005), BAFF inversely correlated with BAFF-R (r = -0.5022, p < 0.006), but not with B-cell count. BAFF was elevated in CKD5 patients (1,276 ± 294 pg/ mL). In RT patients BAFF was significantly higher in those with eGFR Conclusion Serum BAFF concentrations were significantly elevated in pediatric RT patients. They correlated with decreased BAFF-R expression on CD19+ B-cells and impaired allograft function. Our findings of a dysregulated BAFF/BAFF-R axis may be of clinical relevance after renal transplantation and therefore underline the importance of further research into BAFF-dependent mechanisms. Keywords BlyS * B-cells * Tregs * Chronic allograft dysfunction, Introduction For a long time allograft rejection and tolerance were regarded as mainly T-cell dependent. Incidence of acute cellular rejection could be successfully decreased with the use of immunosuppressive drugs [...]

In the course of creating a virtual model of the moated castle Hainchen, district Siegen-Wittgenstein, North Rhine-Westphalia, the individual floors of the castle were reconstructed on the basis of a ground plan from 1777 and then placed on top of each other. It was found that the supposedly exact and dimensioned plan contained considerable inaccuracies. For example, the brickwork is sometimes considerably different from floor to floor, the windows are not arranged in axes and chimney stacks end in the middle of the building. This example shows the possibilities of source criticism of historical plans using virtual reconstructions. [ABSTRACT FROM AUTHOR]

Tb3+ and Eu3+ single-doped barium borate glass and ZBLAN glass are investigated for their photoluminescence (PL) and absolute PL quantum efficiency. In addition, both glass systems are characterized with respect to their color stability in the temperature range from 25 °C to 400 °C. The Tb3+ doped glass shows high color stability over the entire temperature range investigated, whereas the Eu3+ doped glass changes its color appearance with increasing temperature: Eu3+ in ZBLAN glass changes its color appearance from the orange to the red spectral range, whereas the color appearance in borate glass is shifted from the red to the orange-red spectral range. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]