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This is the peer reviewed version of the following article: Delanaye, P., Björk, J., Courbebaisse, M., Couzi, L., Ebert, N., Eriksen, B.O., .... Nyman, U. (2021). Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment. British Journal of Clinical Pharmacology, which has been published in final form at https://doi.org/10.1111/bcp.15132. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Aim: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. Methods: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR Results: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR 2, all equations performed similarly, and for BMI 2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2). The four more recent equations also classified mGFR stages better than CG. Conclusions: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty‐eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss‐of‐function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

The mitigation of climate change demands a decarbonisation of the energy supply of industrialized countries by 2050. This requires fundamental changes of the energy system, high efficiency improvements and a transition to 100% renewable energy supply. A successful transition will need an extremely high acceptance of the general public to be achieved in the given time frame. The necessity of new production, transmission and storage facilities can only by analyzed by highly complex analytical models, which usually are proprietary. In general it is not transparent how the results are derived. To increase the public trust in the results of the underlying modeling, the University of Flensburg is developing the open source model renpass (renewable energy pathways simulation system), for the techno-economic simulation of the future development of the German and European electricity system. This model is supposed to be made available to the general public to scrutinize the assumptions and results of the planning process for the German ‘Energiewende,’ the transition to a 100% renewable electricity supply. The open source energy model has the goal to fulfill the requirements of full transparency and the possibility to image 100% renewable energy target systems as well as today's system and all stages of the system transition on a high regional and time resolution basis. The data input, the simulation as well as the optimization and the output are described. In the end the application possibilities especially for the ‘Energiewende’ in Germany are described and an outlook on future development is given. WIREs Energy Environ 2014, 3:490–504. doi: 10.1002/wene.109 For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.

Despite changes in survival and drug tolerability, nephrotoxicity remains an important complication of chemotherapy. To provide cutting-edge care for children with cancer oncologist must be familiar with their nephrotoxic potential. Careful monitoring of renal function during treatment is therefore indicated. Well-defined guidelines for this are lacking. We reviewed current DCOG protocols and showed that monitoring of renal function during treatment varies widely between protocols. In some protocols recommended renal function measures are inappropriate given the chemotherapy prescribed. Advices on dose modifications in case of renal dysfunction also vary, even with comparable regimens. These differences are unwanted and call for standardization. Pediatr Blood Cancer 2014;61:337–344. © 2013 Wiley Periodicals, Inc.

Background: Advances in diagnostic testing and surgical techniques have resulted in reduced mortality in neonates with congenital heart disease (CHD) and a major concern for neurological morbidity in the presence of preoperative neurological injury. Objectives: To determine the incidence and nature of preoperative cerebral ultrasound abnormalities in neonates with major CHD and to examine the relationship between cerebral abnormalities and the type of CHD. Methods: Retrospective study; inclusion criteria: (1) neonates with major CHD admitted to the NICU over a 3-y period, (2) gestational age > 35 wk, (3) documented preoperative cranial ultrasound available; exclusion criteria: (1) small for gestational age, (2) other congenital anomalies and/or chromosomal abnormalities, (3) a 5-min Apgar score < 7, (4) congenital infection. Cranial ultrasounds (CUS) were reviewed without knowledge of the cardiac defect. CHDs were categorized. Results: Fifty of 108 neonates with CHD met the inclusion criteria. Twenty-one patients (42%) had abnormalities on CUS. Thirteen of these (26%) had widened ventricular and/or subarachnoid spaces, three (6%) lenticulostriate vasculopathy, one (2%) calcification in the basal nuclei, and four (8%) had acute ischaemic changes. Cerebral abnormalities occurred more frequendy in patients with coarctation or hypoplastic left heart syndrome (HLHS) than transposition of the great arteries (TGA) (63% vs 14%; n.s.). Conclusion: There is a high incidence of preoperative cerebral ultrasound abnormalities in this group of neonates with major CHD.

Summary objective In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. design and patients Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Padiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. results The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3·4–7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) Surgery: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6·3 to +9·5 years, leading to severely reduced final height of 137 to 150 cm in adult patients. Patients tended to follow height percentiles of genetic females. One pubertal patient was suicidal due to short stature. (4) Central precocious puberty (CPP): prolonged exposition to adrenal androgens led to CPP in one patient. He was treated with GnRH analogues until gonadectomy. conclusions Patients with CAH and complete virilization have a high risk of being diagnosed late. There are major problems and uncertainties of the patients’ families and the treating physicians concerning gender assignment. Gender identity is disturbed in some patients. In addition, multiple surgical procedures are necessary and short stature as well as central precocious puberty might be important to avoid late sequelae. While some surgical interventions are probably unavoidable, most of these issues could be resolved with an early diagnosis. Thus, especially for these patients, a neonatal screening programme for CAH would be of paramount importance.

To investigate the diagnostic significance of a normal urine sediment in the work-up for fever of unknown origin in neutropenia. Urinary tract infection was defined as ≥10(5) urinary pathogens in the absence of another focus. Pyuria was found in only 1/23 neutropenic episodes compared to 21/31 in controls (P < 0.0001).

Radiofrequency Current Lesions in Young Pigs. Introduction: Radiofrequency current is widely used in children to ablate accessory AV pathways. Previous data in a pig model demonstrated coronary artery obstruction adjacent to radiofrequency current lesions 48 hours and 6 months after energy delivery. In the present study, the long-term effects (>6 months) of radiofrequency current application on coronary artery vessels in young pigs are assessed. Methods and Results: Radiofrequency current (500 kHz) was delivered over 30 seconds in ten piglets (mean body weight 12.8 kg) using a steerahle 6-French catheter with a 4-mm thermistor tip electrode (target temperature 75°C), Lesions were created under fluoroscopic and electrocardiographic guidance at the lateral right atrial (RA) wall above the tricuspid valve orifice, and at the lateral left atrial and left ventricular wall adjacent to the mitral valve orifice. Selective coronary angiography and intravascular ultrasound (IVUS) studies were performed 3, 6, 9, and 12 months after energy application. After 12 months, the lesions were studied pathohistologically. All lesions consisted of compact fibrous tissue, RA lesions extended to the adjacent right coronary artery and led to coronary artery involvement with increased fibrous tissue in the adventitia and media and intimal thickening in three animals. Coronary arterial narrowing was documented by IVUS during follow-up in all three cases 9 months after energy application. Angiography failed to demonstrate coronary pathology in any of the three animals. Conclusion: The risk of late coronary artery lesions must be considered when catheter ablation at the RA wail is planned in children with free-wall accessory AV pathways.

This study was designed to assess the extent of potential discrepancies between intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA) measurement of intrastent minimal luminal diameter and to evaluate the impact of dilation pressures and the balloon:artery ratio on the assessment of the minimal lumen diameter (MLD) by these imaging modalities. IVUS is recommended as an adjunct to angiography to assess stent expansion; however, the extent of potential discrepancies between the two imaging modalities is not well defined. Included were 225 patients in whom coronary Palmaz-Schatz stents were successfully placed after PTCA. IVUS and QCA were performed at the end of the intervention. We compared the MLD assessed by QCA and IVUS in the instent and reference site. The MLD assessed by IVUS and QCA were 2.68 +/- 0.41 mm and 3.08 +/- 0.47 mm (P < 0.001), respectively, at the tightest intrastent site and 3.19 +/- 0.50 mm and 3.17 +/- 0.52 ns at the reference site. There was a correlation between the dilation pressure and the difference between QCA- and IVUS-based intrastent MLD measurement (y = -0.05x + 1.11; r = -0.53; P < 0.0001). At low dilation pressures, a significant difference between the image modalities was found, but after high dilation pressures no discrepancies were detected. No relation was found with the balloon:artery ratio. These data provide clear evidence that in the case of low-pressure dilation, the exclusive reliance on data obtained by QCA will not yield sufficiently accurate information on intrastent MLD, whereas after high dilation pressure, the differences between the imaging modalities are minimized.