A closer look to the timing of orchidopexy in undescended testes and adherence to the AWMF-guideline.

BACKGROUND: To lower the risk of testicular malignancies and subfertility, international guidelines recommend orchidopexy for undescended testis (UDT) before the age of 12-18 months. Previous studies reported low rates of 5-15% of timely surgery. Most of these studies are based on DRG and OPS code-based data from healthcare system institutions that do not distinguish between congenital and acquired UDT. METHODS: In a retrospective study data of all boys who underwent orchidopexy in a university hospital and two outpatient surgical departments from 2009 to 2022 were analyzed. The data differentiates congenital from acquired UDT. RESULTS: Out of 2694 patients, 1843 (68.4%) had congenital and 851 (31.6%) had acquired UDT. In 24.9% of congenital cases surgery was performed before the age of 12 months. The median age at surgery for congenital UDT was 16 months (range 7-202). Over the years there was an increased rate of boys operated on before the age of 2 (40% in 2009, 60% in 2022). The median age fluctuated over the years between 21 and 11 months without a trend to younger ages.. The covid pandemic did not lead to an increase of the median age at surgery. The median time between referral and surgery was 46 days (range 1-1836). Reasons for surgery after 12 months of age were a delayed referral to pediatric surgeries (51.2%), followed by relevant comorbidities (28.2%). CONCLUSION: Compared to recent literature, out data show that a closer look at details enables a more realistic approach. Still, there is no trend towards the recommended age for surgical treatment observable, but the rate of timely operated boys with congenital UDT is significantly higher than stated in literature.

Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma.

PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.

Stabilized Radiation Pressure Acceleration and Neutron Generation in Ultrathin Deuterated Foils.

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

Minimally invasive surgery for neuroblastic tumours: A SIOPEN multicentre study: Proposal for guidelines.

INTRODUCTION: Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. MATERIALS & METHODS: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. RESULTS: A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. CONCLUSIONS: MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours.

[Imaging of renal tumors in children]. / Bildgebung renaler Tumoren im Kindesalter.

CLINICAL/METHODOLOGICAL ISSUE: Renal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children. STANDARD RADIOLOGICAL METHODS: After sonography, magnetic resonance imaging (MRI) is the preferred imaging modality. The task of imaging includes differential diagnosis with the help of morphological and epidemiological criteria. Thorax computed tomography (CT) is introduced for initial staging. METHODOLOGICAL INNOVATIONS: Current studies of diffusion-weighted imaging (DWI)-MRI with analysis of the apparent diffusion coefficient (ADC) histogram indicate the potential to differentiate blastemal or anaplastic high-risk histology nephroblatoma subtypes. Imaging criteria for nephron-sparing surgery are defined and allow an individual therapy option in unilateral and especially in bilateral renal nephroblastoma. PERFORMANCE: In addition to nephroblastoma, the differential diagnosis includes congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney, clear cell sarcoma and renal cell carcinoma. The diagnosis of nephrogenic rests and nephroblastomatosis is challenging. ACHIEVEMENTS: Diagnostic standardization improves diagnosis and therapy of renal childhood tumors, and new prognostic markers may be introduced in the near future.

The structure of enteric human adenovirus 41-A leading cause of diarrhea in children.

Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV-HAdV-F41-determined by cryo-electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.

Management of benign liver tumors.

Benign liver tumors in children are far less frequent than their malignant counterparts. Recently, there have been advances of diagnostic procedures and novel treatments with improved classification as a result. While malignant pediatric liver tumors have been comprehensively addressed by multicenter international tumor trials, benign tumors have more usually relied upon individualised workup and treatment. Due to the rarity and heterogeneity of these different entities, large studies are lacking. In this article the authors highlight the spectrum of benign liver tumors with special focus on specific clinical features, pathology, and treatment.

Dynamics of the Electromagnetic Fields Induced by Fast Electron Propagation in Near-Solid-Density Media.

The propagation of fast electron currents in near solid-density media was investigated via proton probing. Fast currents were generated inside dielectric foams via irradiation with a short (∼0.6 ps) laser pulse focused at relativistic intensities (Iλ^{2}∼4×10^{19} W cm^{-2} µm^{2}). Proton probing provided a spatially and temporally resolved characterization of the evolution of the electromagnetic fields and of the associated net currents directly inside the target. The progressive growth of beam filamentation was temporally resolved and information on the divergence of the fast electron beam was obtained. Hybrid simulations of electron propagation in dense media indicate that resistive effects provide a major contribution to field generation and explain well the topology, magnitude, and temporal growth of the fields observed in the experiment. Estimations of the growth rates for different types of instabilities pinpoints the resistive instability as the most likely dominant mechanism of beam filamentation.

Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes Treg development.

Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in the United States in young adults, but current treatments are only partially effective, making it necessary to develop new, innovative therapeutic strategies. Myelin-specific interleukin (IL)-17-producing T helper type 17 (Th17) cells are a major subset of CD4 T effector cells (Teff ) that play a critical role in mediating the development and progression of MS and its mouse model, experimental autoimmune encephalomyelitis (EAE), while regulatory T cells (Treg ) CD4 T cells are beneficial for suppressing disease. The IL-6/signal transducer and activator of transcription 3 (STAT-3) signaling pathway is a key regulator of Th17 and Treg cells by promoting Th17 development and suppressing Treg development. Here we show that three novel small molecule IL-6 inhibitors, madindoline-5 (MDL-5), MDL-16 and MDL-101, significantly suppress IL-17 production in myelin-specific CD4 T cells in a dose-dependent manner in vitro. MDL-101 showed superior potency in suppressing IL-17 production compared to MDL-5 and MDL-16. Treatment of myelin-specific CD4 T cells with MDL-101 in vitro reduced their encephalitogenic potential following their subsequent adoptive transfer. Furthermore, MDL-101 significantly suppressed proliferation and IL-17 production of anti-CD3-activated effector/memory CD45RO+ CD4+ human CD4 T cells and promoted human Treg development. Together, these data demonstrate that these novel small molecule IL-6 inhibitors have the potential to shift the Teff  : Treg balance, which may provide a novel therapeutic strategy for ameliorating disease progression in MS.

Reticulocytosis in non-anaemic cats and dogs.

OBJECTIVE: To evaluate the proportion of blood samples diagnosed with reticulocytosis without anaemia in cats and dogs and report the aetiology and mortality rate of affected animals. MATERIALS AND METHODS: Retrospective multicentre study including haematological examination of 3956 cats and 11,087 dogs admitted to seven German veterinary clinics (2012 to 2014). The proportion of blood samples with reticulocytosis without anaemia was calculated, and after exclusion of multiple measurements of the same animal, clinical data were evaluated. Animals with reticulocytosis without anaemia were classified as healthy or diseased, and diseased patients were assigned to 12 disease groups. Pretreatment (i.e. non-steroidal anti-inflammatory drugs, glucocorticoids, dipyrone) was recorded. RESULTS: The proportion of blood samples with reticulocytosis without anaemia was 3·1% (124/3956) in cats and 4·4% (492/11,087) in dogs. Overall, 1·8% (2/111) of cats and 1·5% (7/458) of dogs with reticulocytosis without anaemia were healthy. Blood loss/anaemia, cardiac/respiratory disorders, gastrointestinal disorders and inflammatory disorders as well as cancer were the most frequent underlying diseases. Pretreatment was noted in 39·5% (43/111) of cats and 42·4% (194/458) of dogs. The mortality rate was 37·8% (42/111) in cats and 29·7% (136/458) in dogs with reticulocytosis without anaemia; the median survival time in non-survivors was 1 day (range: 0 to 376 days in cats, 0 to 444 days in dogs). CLINICAL SIGNIFICANCE: In both species, reticulocytosis without anaemia was observed in a low proportion of blood samples (dogs>cat). Though a bias towards sick animals is possible in our sample, reticulocytosis without anaemia was mainly seen in diseased animals and associated with a mortality rate of approximately one-third of patients.

Towards an in vitro fibrogenesis model of human vocal fold scarring.

BACKGROUND: Vocal fold (VF) scarring remains a therapeutic dilemma and challenge in modern laryngology. To facilitate corresponding research, we aimed to establish an in vitro fibrogenesis model employing human VF fibroblasts (hVFF) and the principles of macromolecular crowding (MMC). METHODS: Fibrogenesis was promoted by addition of transforming growth factor-ß1 to standard medium and medium containing inert macromolecules (MMC). Hepatocyte growth factor (HGF) and Botox type A were tested for their antifibrotic properties in various doses. Experiments were analyzed with respect to the biosynthesis of collagen, fibronectin, and α-smooth muscle actin using immunofluorescence, silver stain and western blot. RESULTS: MMC led to favourable enhanced deposition of collagen and other extracellular matrix components, reflecting fibrotic conditions. Low doses of HGF were able to dampen profibrotic effects. This could not be observed for higher HGF concentrations. Botox type A did not show any effects. CONCLUSION: Based on the principles of MMC we could successfully establish a laryngeal fibrogenesis model employing hVFF. Our finding of dose-dependent HGF effects is important before going into clinical trials in humans and has never been shown before. Our model provides a novel option to screen various potential antifibrotic compounds under standardized conditions in a short time.

[Innovations in surgical treatment of pediatric solid tumors]. / Innovationen in der chirurgischen Behandlung solider Tumoren im Kindesalter.

The overall survival of children with solid tumors has shown a substantial increase in the past decades due to progress in all of the disciplines involved in the treatment. The poor prognosis for advanced stages of disease and the morbidity related to therapeutic procedures are still a challenge. Innovations in the surgical treatment of solid tumors can contribute to increase the survival rate of affected children and to decrease the treatment-related morbidity. Considering these aspects, the successful implementation of innovations is described based on four examples. (1) Tumor nephrectomy has long been the standard surgical procedure for Wilms tumor/nephroblastoma. Modifications of the surgical technique allow a nephron-sparing resection of the tumor and thereby reducing the long-term effects of nephrectomy. (2) According to the protocols of the International Society of Pediatric Oncology (SIOP) liver transplantation should be used for high-risk hepatoblastoma. Virtual imaging methods based on new software processors enable a more accurate and individual planning of the surgical procedure and an organ-saving extended tumor resection which avoids a transplantation. (3) Mutilating surgical procedures are sometimes necessary for a curative treatment of rhabdomyosarcoma. By combining surgery and brachytherapy mutilating surgical procedures for urogenital rhabdomyosarcomas can be avoided. (4) Pulmonary metastatic nodules can become accessible to minimally invasive resection if CT-guided marking by coil wire is preoperatively performed. In selected cases thoracotomy will be avoided and due to a shorter postoperative course, the time to the subsequent adjuvant chemotherapy will be reduced.

Self-generated surface magnetic fields inhibit laser-driven sheath acceleration of high-energy protons.

High-intensity lasers interacting with solid foils produce copious numbers of relativistic electrons, which in turn create strong sheath electric fields around the target. The proton beams accelerated in such fields have remarkable properties, enabling ultrafast radiography of plasma phenomena or isochoric heating of dense materials. In view of longer-term multidisciplinary purposes (e.g., spallation neutron sources or cancer therapy), the current challenge is to achieve proton energies well in excess of 100 MeV, which is commonly thought to be possible by raising the on-target laser intensity. Here we present experimental and numerical results demonstrating that magnetostatic fields self-generated on the target surface may pose a fundamental limit to sheath-driven ion acceleration for high enough laser intensities. Those fields can be strong enough (~105 T at laser intensities ~1021 W cm-2) to magnetize the sheath electrons and deflect protons off the accelerating region, hence degrading the maximum energy the latter can acquire.

Application of ultrasound imaging biomarkers (HistoScanning™) improves staging reliability of prostate biopsies.

OBJECTIVE: Imaging biomarkers like HistoScanning™ augment the informative value of ultrasound. Analogue image-guidance might improve the diagnostic accuracy of prostate biopsies and reduce misclassifications in preoperative staging and grading. RESULTS: Comparison of 77 image-guided versus 88 systematic prostate biopsies revealed that incorrect staging and Gleason misclassification occurs less frequently in image-guided than in systematic prostate biopsies. Systematic prostate biopsies (4-36 cores, median 12 cores) tended to detect predominantly unilateral tumors (39% sensitivity, 90.9% specificity, 17.5% negative and 50% positive predictive values). Bilateral tumors were diagnosed more frequently by image-guided prostate biopsies (87.9% sensitivity, 72.7% specificity, 50% negative and 96.8% positive predictive values). Regarding the detection of lesions with high Gleason scores ≥ 3 + 4, systematic prostate and image-guided biopsies yielded sensitivity and specificity rates of 66.7% vs 93.5%, 86% vs 64.5%, as well as negative and positive predictive values of 71.2% vs 87%, and 83.3% vs 79.6%, respectively. Potential reason for systematic prostate biopsies missing the correct laterality and the correct Gleason score was a mismatch between the biopsy template and the respective pathological cancer localization. This supports the need for improved detection techniques such as ultrasound imaging biomarkers and image-adapted biopsies.

Collimated protons accelerated from an overdense gas jet irradiated by a 1 µm wavelength high-intensity short-pulse laser.

We have investigated proton acceleration in the forward direction from a near-critical density hydrogen gas jet target irradiated by a high intensity (1018 W/cm2), short-pulse (5 ps) laser with wavelength of 1.054 µm. We observed the signature of the Collisionless Shock Acceleration mechanism, namely quasi-monoenergetic proton beams with small divergence in addition to the more commonly observed electron-sheath driven proton acceleration. The proton energies we obtained were modest (~MeV), but prospects for improvement are offered through further tailoring the gas jet density profile. Also, we observed that this mechanism is very robust in producing those beams and thus can be considered as a future candidate in laser-driven ion sources driven by the upcoming next generation of multi-PW near-infrared lasers.

[Comprehensibility of online-based patient education material in ophthalmology]. / Die Lesbarkeit von onlinebasierten Patienteninformationen in der Augenheilkunde.

BACKGROUND: Investigations have shown that the internet as a source of information in medical issues is increasing in importance. For most patients information delivered or supported by hospitals and universities is considered to be the most reliable, however, the comprehensibility of available information is often considered to be wanting. Comprehensibility scores are formulae allowing a quantitative value for the readability of a document to be calculated. OBJECTIVE: The purpose of this study was to assess data by analyzing the comprehensibility of medical information published on the websites of departments for ophthalmology of German university hospitals. We investigated and analyzed medical information dealing with three eye diseases with potentially severe irreversible damage. METHODS: The websites of 32 departments for ophthalmology of German university hospitals were investigated. Information regarding cataracts, glaucoma and retinal detachment (amotio retinae) were identified and analyzed. All information was systematically analyzed regarding comprehensibility by using the analysis program Text-Lab ( http://www.text-lab.de ) by calculation of five readability scores: the Hohenheim comprehensibility index (HVI), the Amstad index, the simple measure of gobbledygook (G-SMOG) index, the Vienna non-fictional text formula (W-STX) and the readability index (LIX). RESULTS: In 59 cases (61.46 %) useful text information from the homepage of the institutions could be detected and analyzed. On average the comprehensibility of the information was identified as being poor (HVI 7.91 ± 3.94, Amstad index 35.45 ± 11.85, Vienna formula 11.19 ± 1.93, G­SMOG 9.77 ± 1.42 and the LIX 54.53 ± 6.67). CONCLUSION: In most of the cases patient information material was written far above the literacy level of the average population. It must be assumed that the presented information is difficult to read for the majority of the patients. A critical evaluation of accessible information material seems to be desirable and available texts should be amended.

Changes in physical functioning among men and women aged 50-79 years in Germany: an analysis of National Health Interview and Examination Surveys, 1997-1999 and 2008-2011.

BACKGROUND: This study examines changes in physical functioning among adults aged 50-79 years in Germany based on data from two German National Health Interview and Examination Surveys conducted in 1997-1999 (GNHIES98) and 2008-2011 (DEGS1). METHODS: Using cross-sectional data from the two surveys (GNHIES98, n = 2884 and DEGS1, n = 3732), we examined changes in self-reported physical functioning scores (Short Form-36 physical functioning subscale (SF-36 PF)) by sex and age groups (50-64 and 65-79 years). Covariables included educational level, living alone, nine chronic diseases, polypharmacy (≥5 prescribed medicines), body mass index, sports activity, smoking and alcohol consumption. Multimorbidity was defined as ≥2 chronic diseases. Multivariable models were fitted to examine consistency of changes in physical functioning among certain subgroups and to assess changes in mean SF-36 PF scores, adjusting for changes in covariables between surveys. RESULTS: Mean physical functioning increased among adults aged 50-79 years between surveys in unadjusted analyses, but this change was not as marked among men aged 65-79 years who experienced rising obesity (20.6 to 31.5%, p = 0.004) and diabetes (13.0 to 20.0%, p = 0.014). Prevalence of multimorbidity and polypharmacy use increased among men and women aged 65-79 years. In sex and age specific multivariable analyses, changes in physical functioning over time were consistent across subgroups. Gains in physical functioning were explained by improved education, lower body mass index and improved health-related behaviours (smoking, alcohol consumption, sports activity) in women, but less so among men. CONCLUSIONS: Physical functioning improved in Germany among adults aged 50-79 years. Improvements in the population 65-79 years were less evident among men than women, despite increases in multimorbidity prevalence among both sexes. Changes in health behaviours over time differed between sexes and help explain variations in physical functioning. Targeted health behaviour interventions are indicated from this study.

Differences between intrinsic and extrinsic ureteropelvic junction obstruction related to crossing vessels: histology and functional analyses.

PURPOSE: In children, ureteropelvic junction obstruction (UPJO) is mostly caused by intrinsic factors (IUPJO); extrinsic UPJO are rare and often due to crossing vessels (CVs). METHODS: We retrospectively reviewed all data of children with UPJO that underwent surgery in our institution from 2004 to 2011. Analyses included age at surgery, gender, preoperative and postoperative results of ultrasound and renal scans [differential renal function (DRF); signs of obstruction], and pathology reports. Available histological specimens of cases with CV were compared to a random selection of intrinsic cases in a blinded fashion. After additional Masson's trichrome staining, the specimens were scored for fibrosis, muscular hypertrophy, and chronic inflammation. RESULTS: Out of 139 patients with UPJO, 39 cases were associated with CV. Median age at surgery was 68 months (range 2-194) in the CV group and 11.5 months (range 0-188) in IUPJO group. Laparoscopic dismembered pyeloplasty (LDMP) was carried out in 134 and open DMP in five patients. Preoperative ultrasound identified 28/39 cases with CV. DRF below 40 % was more frequently seen in CV patients (p = 0.020). Histological analyses revealed no differences between the CV and IUPJO specimens in total. CV patients with higher grades of muscular hypertrophy had lower preoperative DRF, compared to those with higher preoperative DRF (p = 0.026). Functional recovery after (L)DMP was excellent in both groups. CONCLUSION: We could not find any significant histological differences between CV and IUPJO in children. To obtain excellent functional recovery, surgical procedures with a definite correction of the UPJ should be preferred in paediatric patients with CV.