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Abstract Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment.

Point-of-care ultrasound (POCUS) plays an essential role in pediatric emergency medicine by improving diagnostics and procedural safety. The role of POCUS in the care of pediatric patients in the emergency department has expanded considerably in recent years. Cranial and musculoskeletal imaging has significant potential, yet POCUS has also become a vital tool for common procedures, such as central and difficult peripheral intravenous access. The purpose of this article is to provide an overview of pediatric POCUS applications for cranial, small parts (head, eyes, nose, throat, and soft tissue), musculoskeletal, and common procedural applications, forming the third part of the series.

Acquiring diagnostic ultrasound competencies and skills is crucial in modern health care, and achieving the practical experience is vital in developing the necessary anatomy interpretation and scan acquisition skills. However, traditional teaching methods may not be sufficient to provide hands-on practice, which is essential for this skill acquisition. This paper explores various modalities and instructors involved in ultrasound education to identify the most effective approaches. The field of ultrasound instruction is enriched by the diverse roles of physicians, anatomists, peer tutors, and sonographers. All these healthcare professionals can inspire and empower the next generation of ultrasound practitioners with continuous training and support. Physicians bring their clinical expertise to the table, while anatomists enhance the understanding of anatomical knowledge through ultrasound integration. Peer tutors, often medical students, provide a layer of social congruence and motivation to the learning process. Sonographers provide intensive practical experience and structured learning plans to students. By combining different instructors and teaching methods, success can be achieved in ultrasound education. An ultrasound curriculum organized by experts in the field can lead to more efficient use of resources and better learning outcomes. Empowering students through peer-assisted learning can also ease the burden on faculty. Every instructor must receive comprehensive didactic training to ensure high-quality education in diagnostic ultrasound., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

(1) Objective: This study aims to lay a foundation for noncontact intensive care monitoring of premature babies. (2) Methods: Arterial oxygen saturation and heart rate were measured using a monochrome camera and time-division multiplex controlled lighting at three different wavelengths (660 nm, 810 nm and 940 nm) on a piglet model. (3) Results: Using this camera system and our newly designed algorithm for further analysis, the detection of a heartbeat and the calculation of oxygen saturation were evaluated. In motionless individuals, heartbeat and respiration were separated clearly during light breathing and with only minor intervention. In this case, the mean difference between noncontact and contact saturation measurements was 0.7% (RMSE = 3.8%, MAE = 2.93%). (4) Conclusions: The new sensor was proven effective under ideal animal experimental conditions. The results allow a systematic improvement for the further development of contactless vital sign monitoring systems. The results presented here are a major step towards the development of an incubator with noncontact sensor systems for use in the neonatal intensive care unit.

Emergency ultrasound, or point-of-care ultrasound (POCUS), has been established into daily patient care over the last decades. The use of abdominal and pelvic ultrasound in clinical practice has the potential to improve the efficiency and safety of pediatric emergency care. This article will provide a review of current applications of pediatric emergency abdominal and urogenital ultrasound, forming the second part of the series.

Purpose: To analyze the learning curves of ultrasound novices in fetal echocardiography during structured simulation-based ultrasound training (SIM-UT) including a virtual, randomly moving fetus., Methods: 11 medical students with minimal (< 10 h) prior obstetric ultrasound experience underwent 12 h of structured fetal echocardiography SIM-UT in individual hands-on sessions during a 6-week training program. Their learning progress was assessed with standardized tests after 2, 4, and 6 weeks of SIM-UT. Participants were asked to obtain 11 fetal echocardiography standard planes (in accordance with ISUOG and AHA guidelines) as quickly as possible. All tests were carried out under real life, examination-like conditions on a healthy, randomly moving fetus. Subsequently, we analyzed the rate of correctly obtained images and the total time to completion (TTC). As reference groups, 10 Ob/Gyn physicians (median of 750 previously performed Ob/Gyn scans) and 10 fetal echocardiography experts (median of 15,000 previously performed Ob/Gyn scans) were examined with the same standardized tests., Results: The students showed a consistent and steady improvement of their ultrasound performance during the training program. After 2 weeks, they were able to obtain > 95% of the standard planes correctly. After 6 weeks, they were significantly faster than the physician group (p < 0.001) and no longer significantly slower than the expert group (p = 0.944)., Conclusion: SIM-UT is highly effective to learn fetal echocardiography. Regarding the acquisition of the AHA/ISUOG fetal echocardiography standard planes, the students were able to reach the same skill level as the expert group within 6 weeks., (© 2023. The Author(s).)

Purpose: To analyse the reliability of ultrasound-guided measurement of the cartilage thickness at the medial femoral condyle in athletically active children and adolescents before and after mechanical load in relation to age, sex and type of sport., Methods: Three successive measurements were performed in 157 participants (median/min-max age: 13.1/6.0-18.0 years, 106 males) before and after mechanical load by squats at the same site of the medial femoral condyle by defined transducer positioning. Test-retest reliability was examined using Cronbach's α $\alpha $ calculation. Differences in cartilage thickness were analysed with respect to age, sex and type of practiced sports, respectively., Results: Excellent reliability was achieved both before and after mechanical load by 30 squats with a median cartilage thickness of 1.9 mm (range: 0.5-4.8 mm) before and 1.9 mm (0.4-4.6 mm) after mechanical load. Male cartilages were thicker (p < 0.01) before (median: 2.0 mm) and after (2.0 mm) load when compared to female cartilage (before: 1.6 mm; after: 1.7 mm). Median cartilage thickness was about three times higher in karate athletes (before: 2.3 mm; after: 2.4 mm) than in sports shooters (0.7; 0.7 mm). Cartilage thickness in track and field athletes, handball players and soccer players were found to lay in-between. Sport type related thickness changes after mechanical load were not significant., Conclusion: Medial femoral condyle cartilage thickness in childhood correlates with age, sex and practiced type of sports. Ultrasound is a reliable and simple, pain-free approach to evaluate the cartilage thickness in children and adolescents., Level of Evidence: Level III., (© 2024 The Authors. Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Point-of-care ultrasound (POCUS) plays an essential role in emergency medicine, providing a range of diagnostic and procedural modalities. It does not involve any ionizing radiation and can improve procedural accuracy and safety. The role of POCUS in the care of pediatric patients differs somewhat from that of adult patients, as there are a range of conditions specific to infants and children. The technical background of pediatric POCUS and its current applications for trauma and thoracic scanning are reviewed and illustrated in this first article of this series.

Background: It is a crucial task for physicians to deliver life threatening information to patients (breaking bad news; BBN). Many aspects influence these conversations on both sides, patients, and doctors. BBN affects the patient-physician relationship, patients' outcome, and physicians' health. Many physicians are still untrained for this multi-facetted task and feel unprepared and overburdened when facing situations of BBN. Therefore, any faculties should aim to integrate communication skills into their medical curricula as early as possible. The SPIKES protocol is an effective framework to deliver BBN. Aim of this study is to evaluate the feasibility and obstacles of a BBN seminar and its acceptance and learning curve among undergraduate medical students., Methods: 158 2nd year undergraduate medical students attended a compulsory BBN seminar. The task was to deliver a cancer diagnosis to the patient within a patient - physician role-play in a gyneco-oncological setting before and after a presentation of the SPIKES protocol by the lecturer. The students evaluated important communication skills during these role-plays respectively. Self-assessment questionnaires were obtained at the beginning and end of the seminar., Results: Most students indicated that their confidence in BBN improved after the seminar (p < 0.001). They like the topic BBN to be part of lectures (76%) and electives (90%). Communication skills improved. Lecturer and seminar were positively evaluated (4.57/5)., Conclusion: The seminar significantly increased confidence and self-awareness in delivering life-threatening news to patients among undergraduate medical students. Important learning aspects of BBN and communication skills could be delivered successfully to the participants within a short time at low costs. The integration of communication skills should be implemented longitudinally into medical curricula starting before clinical education to increase the awareness of the importance of communication skills, to decrease anxiety, stress, and workload for future doctors and- most importantly- to the benefit of our patients., (© 2024. The Author(s).)

Malignant focal liver lesions (FLLs) represent various kinds of epithelial and mesenchymal tumors. In pediatric patients, the understanding of pediatric liver diseases and associated imaging manifestations is essential for making accurate diagnosis and differential diagnosis. This paper will discuss the latest knowledge of the common pediatric malignant FLLs, including undifferentiated embryonal sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant rhabdoid tumor. Medical imaging features are not only helpful for clinical diagnosis, but can also be useful in the evaluation and follow-up of pre- and post-treatment. The future perspectives of contrast-enhanced ultrasound (CEUS) enhancement patterns of FLLs in pediatric patients are also mentioned.

Background: Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment., Method: In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1β, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system., Results: MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively)., Conclusion: MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To analyze the feasibility of structured ultrasound simulation training (SIM-UT) in teaching second-trimester ultrasound screening using a high-end simulator with a randomly moving fetus., Methods: This was a prospective, controlled trial. A trial group of 11 medical students with minimal obstetric ultrasound experience underwent 12 hours of structured SIM-UT in individual hands-on sessions within 6 weeks. Learning progress was assessed with standardized tests. Performance after 2, 4, and 6 weeks of SIM-UT was compared with two reference groups ((A) Ob/Gyn residents and consultants, and (B) highly skilled DEGUM experts). Participants were asked to acquire 23 2nd trimester planes according to ISUOG guidelines in a realistic simulation B-mode with a randomly moving fetus as quickly as possible within a 30-minute time frame. All tests were analyzed regarding the rate of appropriately obtained images and the total time to completion (TTC)., Results: During the study, novices were able to improve their ultrasound skills significantly, reaching the physician level of the reference group (A) after 8 hours of training. After 12 hours of SIM-UT, the trial group performed significantly faster than the physician group (TTC: 621±189 vs. 1036±389 sec., p=0.011). Novices obtained 20 out of 23 2nd trimester standard planes without a significant time difference when compared to experts. TTC of the DEGUM reference group remained significantly faster (p<0.001) though., Conclusion: SIM-UT on a simulator with a virtual, randomly moving fetus is highly effective. Novices can obtain standard plane acquisition skills close to expert level within 12 hours of self-training., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether the sex of the newborn affects the lymphocyte subpopulations in the cord blood. Nine B and twenty-one T cell subpopulations were characterized using flow cytometry in human cord blood from sixteen male and twenty-one female newborns, respectively. Except for transitional B cells and naïve B cells, frequencies of B cell counts across all subsets was higher in the cord blood of male newborns than in female newborns. The frequency of naïve thymus-negative Th cells was significantly higher in male cord blood, whereas the remaining T cell subpopulations showed a higher count in the cord blood of female newborns. Our study is the first revealing sex differences in the B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system, urging the need to expand research in this area.

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS. Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1). Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects ( p < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups ( p < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group ( p < 0.049, interaction effect). Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nourkami-Tutdibi, Küllmer, Dietrich, Monz, Zemlin and Tutdibi.)

Background: As neonates are susceptible for many diseases, establishing noninvasive diagnostic methods is desirable. We hypothesized that volatile organic compounds (VOCs) could be successfully measured in diaper samples., Methods: We performed a feasibility study to investigate whether ambient air-independent headspace measurements of the VOC profiles of diapers from premature infants can be conducted using ion mobility spectrometer coupled with multi-capillary columns (B & S Analytik GmbH)., Results: We analysed 39 diapers filled with stool (n = 10) or urine (n = 20) respectively, using empty diapers as a control (n = 9). A total of 158 different VOCs were identified, and we classified the content of the diapers (urine or stool) according to their VOC profiles with a significance level of p < 0.05., Conclusions: We have developed a novel method to study headspace VOC profiles of biosamples using ion mobility spectrometry coupled with multi-capillary columns. Using this method, we have characterized the VOC profiles of stool and urine of preterm neonates. Future studies are warranted to characterize specific VOC profiles in infections and other diseases of the preterm neonate, thus establishing quick and noninvasive diagnostics in the routine care of the highly vulnerable preterm and term neonates., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Significant progress in prenatal care has decreased the incidence of rhesus incompatibility, which may result in hemolytic disease of the fetus and newborn (HDFN). This case report describes an unusual presentation of HDFN in a preterm infant delivered by caesarean section with isolated massive abdominal fluid collection as the leading clinical sign in addition to severe anemia. The immediate drainage of ascites provided transient clinical stabilization with improved pulmonary function in the delivery suite. After admission to the neonatal intensive care unit (NICU), HDFN treatment was initiated. This case report shows the importance of adequately trained staff including neonatologists, pediatricians and NICU nurses in the delivery suite to provide neonatal intensive care for HDFN., (© 2021. The Author(s).)

Pott's puffy tumor (PPT) is an infection of the frontal sinus with subperiosteal and intracranial abscess formation and one of the rare entities in pediatrics. We present a series of four cases of PPT that occurred in two children (6 and 9 years) and in two young adults (17 and 19 years). All patients were treated by an interdisciplinary team of pediatric, neurosurgical, ENT, radiological, and neuroradiological specialists. Antibiotic treatment was combined with single endoscopic surgery in one case and combined endoscopic sinus surgery with an open transcranial approach to drain intracranial abscess formation in three cases. It is important to be aware that PPT occurs in children with the finding of intracranial abscess formation. Therefore, a close interdisciplinary cooperation for successful treatment is needed in this rare disease., (© 2022. The Author(s).)

Background: As childbearing is postponed in developed countries, maternal age (MA) has increased over decades with an increasing number of pregnancies between age 35-39 and beyond. The aim of the study was to determine the influence of advanced (AMA) and very advanced maternal age (vAMA) on morbidity and mortality of very preterm (VPT) infants. Methods: This was a population-based cohort study including infants from the "Effective Perinatal Intensive Care in Europe" (EPICE) cohort. The EPICE database contains data of 10329 VPT infants of 8,928 mothers, including stillbirths and terminations of pregnancy. Births occurred in 19 regions in 11 European countries. The study included 7,607 live born infants without severe congenital anomalies. The principal exposure variable was MA at delivery. Infants were divided into three groups [reference 18-34 years, AMA 35-39 years and very(v) AMA ≥40 years]. Infant mortality was defined as in-hospital death before discharge home or into long-term pediatric care. The secondary outcome included a composite of mortality and/or any one of the following major neonatal morbidities: (1) moderate-to-severe bronchopulmonary dysplasia; (2) severe brain injury defined as intraventricular hemorrhage and/or cystic periventricular leukomalacia; (3) severe retinopathy of prematurity; and (4) severe necrotizing enterocolitis. Results: There was no significant difference between MA groups regarding the use of surfactant therapy, postnatal corticosteroids, rate of neonatal sepsis or PDA that needed pharmacological or surgical intervention. Infants of AMA/vAMA mothers required significantly less mechanical ventilation during NICU stay than infants born to non-AMA mothers, but there was no significant difference in length of mechanical ventilation and after stratification by gestational age group. Adverse neonatal outcomes in VPT infants born to AMA/vAMA mothers did not differ from infants born to mothers below the age of 35. Maternal age showed no influence on mortality in live-born VPT infants. Conclusion: Although AMA/vAMA mothers encountered greater pregnancy risk, the mortality and morbidity of VPT infants was independent of maternal age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nourkami-Tutdibi, Tutdibi, Faas, Wagenpfeil, Draper, Johnson, Cuttini, Rafei, Seppänen, Mazela, Maier, Nuytten, Barros, Rodrigues, Zeitlin and Zemlin.)

Competing Interests: The authors declare no conflict of interest.

Competing Interests: Declaration of interests We declare no competing interests.

Background: Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is associated with poor prognosis. Surfactant protein-D (SFTPD) and mannose-binding lectin (MBL) play a critical role in innate immunity and response to bacterial infections. We investigated serum levels and genetic variants of SFTPD and MBL in CF patients. Method: Thirty-five Caucasian patients homozygous for ΔF508del were genotyped for functional relevant polymorphisms within MBL2 (promoter-221 Y/X, codons 52, 54, and 57) and SFTPD genes (Met11Thr, Ala160Thr, and Ser270Thr). Serum levels of collectins, clinical characteristics, and PA status were correlated with genetic data. Results: Patients age, gender, and PA status did not affect MBL and SFTPD serum concentrations. MBL concentrations were correlated with MBL haplotypes. Patients with chronic Pseudomonas aeroginosa infection (PAC) and MBL insufficiency had a shorter interval between first PA infection and onset of PAC (0.01 vs. 4.6 years, p < 0.04) as well as a lower median age at transition to PAC (9.8 vs. 16.4 years, p < 0.03) compared to MBL sufficient patients with PAC. SFTPD serum level and FEV1% (Spearman r = -0.41, p < 0.03) showed a negative correlation irrespective of PA infection status. The hazard ratio to PA acquisition was increased in carriers of the SFTPD haplotype 11Thr-160Ala-270Ser compared to carriers of the common 11Met-160Thr-270Ser haplotype [HR 3.0 (95%CI: 1.1-8.6), p < 0.04]. Conclusion: MBL insufficiency leads to a shorter interval between first PA infection and onset of chronic infection. Susceptibility to PA acquisition is associated with SFTPD genetic variants with 11Thr-160Ala-270Ser as risk haplotype for early PA infection. This may be due to presence of threonine associated with oligomeric structure of SFTPD and binding ability to bacteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nourkami-Tutdibi, Freitag, Zemlin and Tutdibi.)

Background: In patients with neurosurgical interventions requiring dura reconstruction, the use of bovine graft material may be required., Patients and Methods: Case report., Results: We present a 12-year-old girl with a profound graft reaction with severe neurologic symptoms mimicking post-neurosurgical bacterial meningitis after resection of an infra-tentorial brain tumour., Conclusion: It is important to take into consideration this rare clinical entity in children and adults after dura reconstruction using allogenic graft (bovine) material in order to avoid the unnecessary use of antibiotics and antiviral drugs.

Aim: We sought to improve retention of neonatal resuscitation skills by modifying step 3 through additional functional verbalisation in Peyton's four-step approach (P4S)., Methods: Newborn life support (NLS) training was performed in a simulation-based setting. In contrast to the traditional approach, students taught with the modified approach were requested to explain every step of their performance in Peyton's step 3. A total of 123 students were allocated into both experimental groups. Students were then assessed by megacode on day four (initial assessment) and 6 months (follow-up assessment)., Results: Both groups showed similar scorings in the initial, follow-up assessment and in mean change. On initial megacode, time to start with initial inflation and post-resuscitation care was significantly faster in the control group. All showed a significant loss of performance irrespective of modification in step 3 in the follow-up assessment. Only time until start with post-resuscitation care shows a significant group difference in mean change between initial and follow-up with increasing time in the control and decreasing time span in intervention group., Conclusion: Both methods showed equal levels of knowledge acquisition and long-term decline in NLS performances. Verbalisation in step 3 influenced speed of applied NLS performance., (© 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: Osteopontin (OPN) has been investigated as a biomarker for cancer and nonmalignant diseases during the last decades. Data about OPN as a potential biomarker in childhood diseases are still sparse, and reference values are not available in children. We aimed to establish reference values for children from birth to young adulthood and evaluate whether there are age-, gender-, and weight-specific differences., Method: Umbilical cord blood and blood plasma samples of 117 children were collected in the Children's Hospital of Saarland University in Homburg/Saar. OPN levels were measured by ELISA, and statistical analysis was performed using SPSS software., Results: Neonates, infants, toddlers, young children, adolescents, and adults were divided into the following six age groups: newborns (birth), infancy and toddlers (0-24 months), early childhood (3-6 years), middle childhood (7-11 years), adolescence (12-18 years), and adults (> 18 years). Highest blood OPN levels were found in the group of 0-1 years of age. OPN blood levels declined significantly with age (Spearman r = -0.874; P < 0.001)., Conclusion: Our work is the first prospective and systematic study analyzing OPN cord blood and blood plasma levels in children of all ages. It is the first study yielding reference values for different age groups from birth to young adulthood. Our data give insight on how OPN in umbilical cord blood and OPN in blood plasma are physiologically influenced during childhood development and growth with high OPN levels after birth and a constant age-related decline until the age of 14, when OPN levels reach similar values to those measured in adults., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Background:  Diagnostic ultrasound has a crucial importance in clinical settings, especially in intensive care medicine where bedside ultrasound has become indispensable. Medical students as well as residents therefore have a strong interest in learning this useful skill. Since staff resources are limited, more and more universities are using student tutors in a peer-assisted learning concept (PAL) to teach medical students early in their training. To date, there is very sparse data about knowledge retention after peer-assisted teaching. The aim of this study was to evaluate whether PAL is a suitable method for teaching complex skills like abdominal ultrasound and to evaluate whether students do achieve adequate long-term knowledge retention after peer-assisted teaching., Method:  A total of 40 volunteer 3 rd to 5 th year students were randomly assigned to a basic abdominal ultrasound course in small training groups of 5 persons each. Participants were evaluated using a pre-post-test design by a validated objective structured clinical examination (OSCE) before and immediately after the course. To measure the retention of knowledge, 15 former participants were randomly selected to repeat the OSCE assessment after one year., Results:  All groups showed a significant improvement in practical skills and knowledge gain after the training with mean values of 13.1 for pre-test compared to 83.5 (maximum 100 points) for post-test (p < 0.001). The overall score achieved after one year was 78.7 and did not significantly differ from the post-test result., Conclusion:  PAL is effective for teaching abdominal ultrasound. Students were able to accomplish a satisfactory level of ultrasound skills. We further demonstrated that PAL can assure long-term knowledge retention., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Congenital mesoblastic nephroma (MN) is a rare pediatric renal tumor representing approximately 5% of all pediatric renal tumors. Three different types of MN are distinguished histologically: classical, cellular, and mixed. A frequent genetic alteration is the translocation t(12;15) resulting in a fusion of the ETV6 gene on 12p13 and the NTRK3 gene on 15p15 that occurs almost exclusively in cellular MN. The aim of this study was to determine translocation status of a large cohort of MN with respect to tumor subtype and outcome., Procedure: In total, clinical data from 111 patients were available. Sixty-seven tumors were classical MN (51%), 29 cellular MN (31%), and 15 were mixed MN (18%). From these 111 cases, 79 were analyzed by FISH and RT-PCR., Results: All classical and mixed MN were translocation negative. Seventeen out of 29 (58%) cellular MN harbored the ETV6-NTRK3 translocation. Five-year relapse-free survival (RFS) and overall survival (OS) were 93.2% and 96.8% for the complete cohort. All seven relapses occurred in translocation negative tumors. Five-year RFS was significantly inferior for cellular and mixed MN compared to classic MN (89%, 80%, and 98%), whereas 5-year OS was similar (93%, 96%, and 98%). Within the group of cellular MN, patients having translocation-positive tumors had a significantly superior RFS (5-year RFS: 100% vs. 73%)., Conclusion: The majority of cellular MNs harbor the ETV6-NTKR3 gene fusion, whereas all classic- and mixed-type MNs were translocation negative. Within the cellular subgroup, patients having translocation-positive tumors had a significantly superior RFS., (© 2017 Wiley Periodicals, Inc.)

Background: Malignant rhabdoid tumor of the kidney (MRTK) is the most aggressive childhood renal tumor with overall survival (OS) rates ranging from 22% to 42%. Whether high-dose chemotherapy with autologous stem-cell transplantation (HDSCT) in an intensive first-line treatment offers additional benefit is an ongoing discussion., Methods: A retrospective analysis of all 58 patients with MRTK from Austria, Switzerland, and Germany treated in the framework of consecutive, prospective renal/rhabdoid tumor studies SIOP9/GPO, SIOP93-01/GPOH (where SIOP is International Society of Pediatric Oncology and GPOH is German Society of Pediatric Oncology and Hematology), SIOP2001/GPOH, and European Rhabdoid Tumor Registry from 1991 to 2014., Results: Median age at diagnosis was 11 months. Fifty percent of patients had metastases or multifocal disease at diagnosis (Stage IV). Local stage distribution was as follows: not done/I/II/III-1/6/11/40. Fifteen (26%) patients underwent upfront surgery. Thirty-seven (64%) patients achieved a complete remission, 17 (29%) relapsed, 34 (59%) died of disease progression, and two (3%) died of treatment-related complication. Mean time to the first event was 3.5 months. Two-year EFS/OS (where EFS is event-free survival) for the whole group was 37 ± 6%/38 ± 6%. Metastases/multifocal disease, younger age, and local stage III were associated with significantly inferior survival. Eleven (19%) patients underwent HDSCT (carboplatin + thiotepa, n = 6; carboplatin + etoposide + melphalan, n = 4; others, n = 1); 2-year OS in this group was 60 ± 15% compared to 34 ± 8% in the non-HDSCT group (P = 0.064). However, the time needed from radiologic to histologic diagnosis, stem-cell harvest, and HDSCT must also be taken into account to avoid selection bias by excluding the highest risk group with early progression (<90 days). Thus, 2-year EFS only for patients without progression until day 90 was 60 ± 16% consolidated by HDSCT compared to 62 ± 11% without (P = 0.8)., Conclusion: Our retrospective analysis suggests comparable outcomes for patients with and without HDSCT, if adjusted for early disease progression., (© 2017 Wiley Periodicals, Inc.)

Background: Nephroblastoma (or Wilms tumor-WT) is the most common childhood kidney cancer. In Europe, nephroblastoma is treated with preoperative chemotherapy without histological confirmation by biopsy. Therefore, minimal-invasive diagnostic markers confirming nephroblastoma diagnosis are highly warranted., Procedure: In our study, we aim to identify circulating miRNAs with diagnostic potential for differentiating nephroblastoma from controls. We determined the level of 19 miRNAs in serum of 32 patients with nephroblastoma and 12 controls with quantitative real-time PCR. Three miRNAs were further tested in an independent validation set including sera of patients with renal tumors other than Wilms., Results: In total, 14 miRNAs showed significantly higher abundance in serum of patients with nephroblastoma than in controls. The miRNAs with highest diagnostic potentials included miRs-130b-3p, -100-5p, and -143-3p with an AUC of 0.94, 0.90, and 0.89, respectively. A signature based on these three miRNAs to differentiated patients from controls with an accuracy of 84.58%, a sensitivity of 76.67%, and a specificity of 92.5%. Higher expression of miRs-100-5p and -130b-3p was confirmed in an independent validation set. The signature based on miRs-100-5p and -130b-3p differentiated patients with nephroblastoma from healthy controls with an accuracy, sensitivity, and specificity of 79.6%, 69.2%, and 90.0%, respectively., Conclusion: In summary, we provide first evidence that serum miR-100-5p and -130b-3p hold potential as biomarker for WT irrespective of the subtype and that expression level of these miRNA in serum is unaffected by differences in serum collection., (© 2015 Wiley Periodicals, Inc.)

Case reports and in vitro testing suggest sensitivity of malignant rhabdoid tumor of the kidney (MRTK) to anthracyclines. Prospective study data supporting doxorubicin's efficacy is lacking. We compared the change of tumor volume in the kidney to upfront treatment with either actinomycin D and vincristine (AV) or doxorubicin-intensified AV (AVD) in all patients with MRTK, who had been treated from 1991-2013 in Austria, Switzerland, and Germany in the framework of three prospective Société International d'Oncologie Pédiatrique/Gesellschaft für Pädiatrische Onkologie und Hämatologie nephroblastoma studies. A total of 37 patients with MRTK received pre-operative chemotherapy (AV, n = 19; AVD, n = 18). Initial and tumor volume after pre-operative treatment was reported in all patients who received AV and 15 of 18 (83%) patients who received AVD. Mean tumor volume at diagnosis was 247 (±48) mL in the AV cohort and 345 (±47) mL in the AVD cohort. Mean volume at surgery was 249 (±46) mL and 137 (±27) mL, respectively. Relative change in tumor volume was +19 (±16)% in patients who received AV and -63 (±26)% in patients who received AVD (P < 0.001). Change in volume to AV ranged from -60 to +224%, whereas the change to AVD ranged from -9 to -92%. We provide good evidence of doxorubicin's activity in MRTK in vivo by demonstrating a significantly better response to neoadjuvant AVD compared with AV alone., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Wilms Tumor (WT) is the most common renal childhood tumor. Recently, we reported a cDNA microarray expression pattern that varied between WTs with different risk histology. Since the Societé Internationale d'Oncologie Pédiatrique (SIOP) in Europe initiates treatment without a histological confirmation, it is important to identify blood-born markers that indicate WT development. In a multicenter study, we established an autoantibody signature by using an array with 1,827 recombinant E. coli clones. This array was screened with sera of patients with WT recruited by SIOP or the Children's Oncology Group (COG). We report an extended number of antigens that are reactive with autoantibodies present in sera from patients with WT. We established an autoantibody signature that separates untreated patients with WT recruited in SIOP from non-WT controls with a specificity of 0.83 and a sensitivity of 0.82 at standard deviations of 0.02 and 0.04, respectively. Likewise, patients recruited in the COG in the United States were separated from the controls with an accuracy of 0.83 at a standard deviation of 0.02. Proteins that were most significant include zinc finger proteins (e.g., ZFP 346), ribosomal proteins and the protein fascin that has been associated with various types of cancer including renal cell carcinoma. Our study provides first evidence for autoantibody signatures for WTs and suggests that these may be most informative before chemotherapy. We present the first multicenter study of autoantibody signatures in patients with WT. We established an autoantibody signature that separates patients with WT from controls., (Copyright © 2011 UICC.)

Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8%, a sensitivity of 87.0% and a specificity of 86.7%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.