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Abstract Brain tumor volumes as assessed by magnetic resonance imaging (MRI) do not always spatially overlap with biological tumor volumes (BTV) measured by [18F]Fluoroethyltyrosine positron emission tomography ([18F]FET PET). We prospectively investigated volumetric patterns based on the extent of tumor volume overlap between the two modalities. Eighty-six patients with newly diagnosed glioma who had undergone MRI and [18F]FET PET between 2007 and 2009 were included in this prospective study and (re-)classified according to CNS WHO 2021 (Classification of Tumors of the Central Nervous System by the World Health Organization). Four different patterns of volume overlap were defined mathematically according to the extent of overlap between MRI-based T2 tumor volume (non-enhancing tumor volume, nCEV) and BTVs. Progression-free (PFS) and overall survival (OS) were determined. Seventy patients were diagnosed with isocitrate dehydrogenase wildtype (IDHwt) glioblastoma and 16 with IDH-mutant glioma, respectively. The most common pattern was characterized by a larger non-contrast-enhancing tumor volume (nCEV) that enclosed all or most of the BTV and was observed in 46 patients (54%) (pattern 1). This pattern was more frequent in IDH-mutant gliomas than in IDH-wildtype glioblastoma (81% versus 47%, p = 0.02). In multivariate analyses, pattern 1 was associated with prolonged PFS (HR 0.59; 95 CI 0.34-1.0; p = 0.05), but not OS (HR 0.66; 95 CI 0.4–1.08; p = 0.1). For OS, presence of an IDH mutation (p = 0.05) and lower age (p = 0.03) were associated with prolonged OS. The spatial relation between nCEV and BTV varies within and between glioma entities. Most frequently, a larger nCEV encases the BTV. Some patients show spatially dissociated nCEVs and BTVs. Not accounting for this phenomenon in surgery or radiotherapy planning might lead to undertreatment.

Abstract Background Positive effects of brace treatments in adolescent idiopathic scoliosis patients on gait were proven. Aim Therefore, this study examined whether the influence of brace therapy in combination with Schroth therapy influencing the plantar pressure distribution, pre and post intensive rehabilitative inpatient treatment. Design Prospective cohort study, longitudinal. Setting Scoliosis rehabilitation clinic “Asklepios Katharina-Schroth-Klinik” (Bad Sobernheim, Germany). Population Twenty (14f/6m) patients (12–16 years) had a medically diagnosed moderate idiopathic scoliosis (Cobb angle 20–50°, Median 30°) and an indication for combined brace and Schroth therapy with an inpatient stay (4 weeks) at the Asklepios Katharina Schroth Clinic (Germany). Methods At the beginning (T1) and at the end of the stay (T2), the plantar pressure distribution with (A) and without wearing a brace (B) was recorded (walking distance 10 m). Results No significant differences between the left and right foot were found at baseline (T1). The T1 - T2 comparison of one foot revealed significant differences (p ≤ 0.05 − 0.001, respectively) for (A): mean pressure right midfoot, loaded area total left foot, left midfoot, left inner ball of foot, right midfoot, impulse total right foot, right midfoot and for (B): mean pressure right midfoot, right outer ball of foot, loaded area total right foot, right heel, right midfoot, impulse right heel, right midfoot, right outer ball of foot. Conclusions A combined brace and Schroth therapy maintains the initial symmetrical plantar pressure distribution over the duration of four weeks since the significant differences fall within the range of measurement error. Clinical rehabilitation impact The insole measuring system can be used to objectively support therapeutic gait training as part of rehabilitation and to assess insole fitting based on foot shape. Due to its convenient handling and rapid data acquisition, it may be a suitable method for interim or follow-up diagnostics in the treatment of idiopathic scoliosis.

PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.

Introduction: Neuroinflammation evaluation after acute ischemic stroke is a promising option for selecting an appropriate post-stroke treatment strategy. To assess neuroinflammation in vivo, translocator protein PET (TSPO PET) can be used. However, the gold standard TSPO PET quantification method includes a 90 min scan and continuous arterial blood sampling, which is challenging to perform on a routine basis. In this work, we determine what information is required for a simplified quantification approach using a machine learning algorithm. Materials and Methods: We analyzed data from 18 patients with ischemic stroke who received 0–90 min [18F]GE-180 PET as well as T1-weigted (T1w), FLAIR, and arterial spin labeling (ASL) MRI scans. During PET scans, five manual venous blood samples at 5, 15, 30, 60, and 85 min post injection (p.i.) were drawn, and plasma activity concentration was measured. Total distribution volume (VT) was calculated using Logan plot with the full dynamic PET and an image-derived input function (IDIF) from the carotid arteries. IDIF was scaled by a calibration factor derived from all the measured plasma activity concentrations. The calculated VT values were used for training a random forest regressor. As input features for the model, we used three late PET frames (60–70, 70–80, and 80–90 min p.i.), the ASL image reflecting perfusion, the voxel coordinates, the lesion mask, and the five plasma activity concentrations. The algorithm was validated with the leave-one-out approach. To estimate the impact of the individual features on the algorithm’s performance, we used Shapley Additive Explanations (SHAP). Having determined that the three late PET frames and the plasma activity concentrations were the most important features, we tested a simplified quantification approach consisting of dividing a late PET frame by a plasma activity concentration. All the combinations of frames/samples were compared by means of concordance correlation coefficient and Bland-Altman plots. Results: When using all the input features, the algorithm predicted VT values with high accuracy (87.8 ± 8.3%) for both lesion and non-lesion voxels. The SHAP values demonstrated high impact of the late PET frames (60–70, 70–80, and 80–90 min p.i.) and plasma activity concentrations on the VT prediction, while the influence of the ASL-derived perfusion, voxel coordinates, and the lesion mask was low. Among all the combinations of the late PET frames and plasma activity concentrations, the 70–80 min p.i. frame divided by the 30 min p.i. plasma sample produced the closest VT estimate in the ischemic lesion. Conclusion: Reliable TSPO PET quantification is achievable by using a single late PET frame divided by a late blood sample activity concentration.

Objective: This study investigates if an inpatient rehabilitation therapy (brace therapy and Schroth therapy) for six weeks contributes to an improvement in lung function of the patients. Design: Retrospective study. Setting: Scoliosis rehabilitation clinic “Asklepios Katharina-Schroth-Klinik” (Bad Sobernheim, Germany). Participants: In 253 female patients a lung function examination was performed at entry and at the end of their inpatient rehabilitation stay. Of these, 61 patients underwent Schroth therapy (group 1); 192 patients underwent the combination of brace and Schroth therapy (group 2). Intervention: Lung function parameters under the influence of Schroth and Schroth and brace therapy within a rehabilitative stay. Main measures: The parameters of IVC (inspiratory vital capacity), FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 s) and the Tiffeneau index (FEV/FVC) related to patient-specific reference values were evaluated with regard to potential ventilation disorders. Results: There were significant improvements for IVC +2.56 %, FVC +3.99 %, FEV1 +2.36 % for the first stay (IVC and FVC 2nd, 3rd stay). The comparison of patients with vs. without additional brace therapy showed no significances. For the long-term analysis the parameters approached the reference values of age-matched, healthy female subjects. The greater the Cobb angle in the thoracic region, the significantly worse almost each of the measured parameters are. Conclusion: An inpatient rehabilitation therapy contributes to an improvement in lung function (IVC, FVC and FEV1). A second, and even a third, follow-up stay still led to a measurable improvement in lung function, albeit to a lesser extent.

Abstract Background Work-related forced postures, such as prolonged standing work, can lead to complaints in the lower back. Current research suggests that there is increased evidence of associations between patients with low back pain (LBP) and reduced lordosis in the lumbar spine and generally less spinal tilt in the sagittal plane. The aim of this study is to extend the influence of LBP to other parameters of upper body posture in standing, taking into account the rotational and frontal planes. Methods The study included a no-LBP group (418 males, 412 females, aged 21–65 years) and an LBP group (138 subjects: 80 females, 58 males, aged 18–86 years) with medically diagnosed lumbar spine syndrome (LSS). The “ABW BodyMapper” back scanner from ABW GmbH in Germany was used for posture assessment using video raster stereography. Statistical analyses employed two-sample t-tests or Wilcoxon-Mann-Whitney-U tests to assess the relationship between the LBP/no-LBP groups and back posture parameters. Linear and logarithmic regressions were used with independent variables including group, sex, height, weight and body mass index (BMI). Significance level: α = 0.05 (95% confidence). Results The regression analysis showed that sagittal parameters of the spine (sagittal trunk decline, thoracic and lumbar bending angle, kyphosis and lordosis angles) depend primarily on sex, age, BMI, height and/or weight but not on group membership (LBP/no-LBP). In the shoulder region, a significant dependency between group membership and scapular rotation was found. In the pelvic region, there were only significant dependencies in the transverse plane, particularly between pelvic torsion and BMI, weight, height and between pelvic rotation and group membership, age and sex. Conclusion No difference between the patients and healthy controls were found. In addition, sex appears to be the main influencing factor for upper body posture. Other influencing factors such as BMI, height or weight also seem to have a significant influence on upper body posture more frequently than group affiliation.

Objective There has not been a theoretical test run in Germany that compares different navigation systems with an industry solution (MapTrip112). The aim of this study was to compare navigation systems to elucidate whether the emergency response time (ERT) was reduced and, consequently, whether the adherence to the travel time improved.Design Prospective, simulation study, cross-sectional study.Setting Offices of the Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe University Frankfurt (60 590 Frankfurt am Main, Germany). The situation-adaptable industry navigation solution MapTrip112 was tested in its ‘Lights and Siren(s) (L&S)’ mode in comparison to the TomTom and Google Maps navigation systems. MapTrip112 was set to calculate a route that takes special emergency rights of way into account.Outcome measures All three navigation systems simultaneously calculated the distances and durations of fictitious routes. Three scenarios were tested: the University Hospital Frankfurt (60 596 Frankfurt am Main, Germany) and the Central Fire Station 1 (60435 Frankfurt am Main, Germany) served as the starting points for the urban routes, while the Odenwald Health Centre (64 711 Erbach, Germany) served as the starting point for rural routes. The routes’ endpoints were arbitrarily chosen locations inside the customary operational radius. The routes were selected for short and long distances as well as for different periods, including weekdays, weekends and evening rush hour (4–7 pm), in the German cities of Frankfurt am Main and Odenwaldkreis (Southern Hesse).Results The time and distance were calculated for a total of 4650 trips. When comparing travel times and distances between rural and urban areas as well as between weekdays and weekends, statistically significant results were obtained (p

Background: The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. Methods: A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). Results: Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1–391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5–142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00–0.69) and the right lacrimal gland (median 0.59, range 0.42–0.78). Conclusions: The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registration: NCT05871021

Abstract Background To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. Methods Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). Results Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). Conclusion LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. Relevance statement MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. Key points • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction. Graphical Abstract

Abstract Background The research project GAIN (working healthy in inclusion companies) deals with the topics of health and work in inclusive companies. Due to a great need for research on (occupational) health (e.g. physical and mental health status) and workplace design in companies employing people with disabilities, this project pursues the primary goal of generating information for the development and implementation of health-preserving measures within the framework of occupational health and safety, and risk assessment, for employees with and without impairments in inclusive companies. Methods Within the framework of the project, the employees of three inclusive companies will be examined with the help of an interdisciplinary and triangulative approach. Using quantitative and qualitative methods, specific physical workloads and hazards will be investigated by means of baseline screening methods and measurement techniques, specifically among employees with physical disabilities and impairments. In the statistical analysis, descriptive methods will be used to record the current state, while inferential statistical methods will be used to evaluate health maintenance measures. Inferential statistics for continuous data with confidence intervals based on the statistical parametric mapping (SPM) method will also be performed. The significance level will be set at 5%. Qualitative methods will be used to analyse structures and working conditions within the companies, with particular attention to the specific construction of the relationship between work, health and disability. Conclusions The structures in inclusion companies must be specifically designed to support and promote the understanding of work and health in relation to the idea of one’s own body, its positioning in space and its performance. These characteristics are to be identified in the course of the project and bundled into best-practice recommendations. Furthermore, it is the aim of the research project to derive recommendations for action at its conclusion and to present further advice for the promotion of health in inclusive companies.

Background and purpose: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept. Materials and methods: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans. Results: Median NTCP of the reference plan (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11–0.29) and 0.42 (range 0.18–0.54), respectively. NTCPex was a median of 1.77 (range 1.60–1.99) times as high as the NTXPref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66–2.35). The defined constraints for the organs at risk were feasible. Conclusion: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.

Abstract TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity of cell populations that contribute to the TSPO-PET signal, imaging interpretation may be challenging. We therefore evaluated TSPO enrichment/expression in connection with its underlying histopathological and molecular features in gliomas. We analyzed TSPO expression and its regulatory mechanisms in large in silico datasets and by performing direct bisulfite sequencing of the TSPO promotor. In glioblastoma tissue samples of our TSPO-PET imaging study cohort, we dissected the association of TSPO tracer enrichment and protein labeling with the expression of cell lineage markers by immunohistochemistry and fluorescence multiplex stains. Furthermore, we identified relevant TSPO-associated signaling pathways by RNA sequencing. We found that TSPO expression is associated with prognostically unfavorable glioma phenotypes and that TSPO promotor hypermethylation is linked to IDH mutation. Careful histological analysis revealed that TSPO immunohistochemistry correlates with the TSPO-PET signal and that TSPO is expressed by diverse cell populations. While tumor core areas are the major contributor to the overall TSPO signal, TSPO signals in the tumor rim are mainly driven by CD68-positive microglia/macrophages. Molecularly, high TSPO expression marks prognostically unfavorable glioblastoma cell subpopulations characterized by an enrichment of mesenchymal gene sets and higher amounts of tumor-associated macrophages. In conclusion, our study improves the understanding of TSPO as an imaging marker in gliomas by unveiling IDH-dependent differences in TSPO expression/regulation, regional heterogeneity of the TSPO PET signal and functional implications of TSPO in terms of tumor immune cell interactions.