University Medical Center Freiburg

The escalating prevalence of anterior cruciate ligament (ACL) injuries in sports necessitates innovative strategies for ACL reconstruction. In this study, we propose a multiphasic bone-ligament-bone (BLB) integrated scaffold as a potential solution. The BLB scaffold comprised two polylactic acid (PLA)/deferoxamine (DFO)@mesoporous hydroxyapatite (MHA) thermally induced phase separation (TIPS) scaffolds bridged by silk fibroin (SF)/connective tissue growth factor (CTGF)@Poly(l-lactide-co-ε-caprolactone) (PLCL) nanofiber yarn braided scaffold. This combination mimics the native architecture of the ACL tissue. The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL. In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes, while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells (BMSCs) and promoted the migration and tubular formation of human umbilical vein endothelial cells (HUVECs). In rabbit models, the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances. The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration, while CTGF improved collagen formation and ligament healing. Collectively, the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction. Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.

Objectives: To analyze the effect of implant treatment in edentulous patients reha- bilitated with implant-supported fixed complete dentures (IFCDs) or implant overden- tures (IODs) on dental patient-reported outcomes (dPROs). Materials and Methods: In January 2022, Medline, Embase, CINAHL, Cochrane Library, PubMed Central, Web of Science, and ClinicalTrials.gov were screened for prospective clinical studies on completely edentulous patients treated with IFCDs and/or IODs, reporting pre-treatment and follow-up dPROs. Hedges' g effect sizes (ES) with corresponding 95% confidence intervals (CI) were calculated. Afterward, meta-analyses were conducted using random effect models. Results: A total number of 1608 records was initially identified. Of those, 28 studies reporting dPROs from 1457 patients were finally included. The applied dental patient- reported outcome measures (dPROMs) included several versions of the Oral Health Impact Profile (OHIP) or specific items assessing satisfaction with Visual Analogue Scales (VAS). The overall ES was large for rehabilitation with IFCDs (1.68 [CI: 1.15, 2.20]) and IODs (1.26 [CI: 0.99, 1.52]) with no significant difference (p = .165) between the two. Denture stability was the only factor rated significantly higher for IFCDs (ES difference: 2.37 [CI: 0.21, 4.54]; p = .032). Subgroup analyses revealed moderately higher ES for IODs on two implants relative to one implant (ES difference: 0.73 [CI: 0.34, 1.12]; p < .001). Conclusions: There is a strong positive effect of implant treatment in edentulous pa- tients, independent of the type of prosthetic rehabilitation. In patients seeking high stability, IFCDs may be preferable. In mandibular IODs on a single implant, there was a significantly positive effect of an additional implant on dPROs.

Increasing pharmaceutical expenditure challenges the sustainability and accessibility of healthcare systems across Europe. Confidentiality restraints hinder assessment of actual prices of Orphan Medicinal Products (OMPs). Hence, we assessed the real prices of brand-name OMPs around market exclusivity expiry (MEE). We aimed to explore developments in published list prices (LPs) and confidential hospital purchase prices (PPs) of brand-name OMPs relative to their market exclusivity status in Western European countries with similar GDPs. We analyzed LPs and PPs of 13 selected OMPs purchased by university hospitals in Western European countries between 2000 and 2020. For confidentially reasons, proportions were used, with the Dutch LPs of the selected OMPs at the year of MEE serving as reference values. PPs included pre-purchase discounts. Rebates were not considered. Data were analyzed from hospitals in Denmark (DK) (n = 1), France (FR) (n = 1), Germany (DE) (n = 2), and the Netherlands (NL) (n = 1). Average LPs and PPs of included OMPs dropped gradually but limited over time, with no explicit price drop after MEE. LP levels differed more per country than PP levels: LP range before MEE was 164% (DE)–101% (FR) and after MEE was 135% (DE)–82% (FR); PP range before MEE was 150% (DE)–102% (FR) and after MEE was 107% (DE)–80% (FR). Overall differences between LPs and PPs were < 3% in all countries, except for Denmark. No evident price drops of included brand-name OMPs were observed around MEE and differences in purchase prices are modest in the selected Western European countries. Results were not subject to significance testing. More robust data are needed to strengthen negotiations with suppliers.

Objective The objectives of the study were to assess the survival, failure, and technical complication rates of implant‐supported fixed dental prosthesis (iFDPs) with pontic or splinted crown (iS p C) designs in the posterior area and compare the influence of prosthetic materials and prosthetic design on the outcomes. Methods Electronic and manual searches were performed to identify randomized‐, prospective‐, and retrospective clinical trials with follow‐up time of ≥12 months, evaluating the clinical outcomes of posterior iFDPs with pontic or iS p Cs. Survival and complication rates were analyzed using robust Poisson's regression models. Results Thirty‐two studies reporting on 42 study arms were included in the present systematic review. The meta‐analysis of the included studies indicated estimated 3‐year survival rates of 98.3% (95%CI: 95.6–99.3%) for porcelain‐fused‐to‐metal (PFM) iFDPs, 97.5% (95%CI: 95.5–98.7%) for veneered zirconia (Zr) iFDPs with pontic, 98.9% (95%CI: 96.8–99.6%) for monolithic or micro‐veneered zirconia iFDPs with pontic, and 97.0% (95%CI: 84.8–99.9%) for lithium disilicate iFDPs with pontics. The survival rates for different material combination showed no statistically significant differences. Veneered restorations, overall, showed significantly ( p < .01) higher ceramic fracture and chipping rates compared with monolithic restorations. Furthermore, there was no significant difference in survival rates (98.3% [95%CI: 95.6–99.3%] vs. 99.1% [95%CI: 97.6–99.7%]) and overall complication rates between PFM iFDPs with pontic and PFM iS p Cs. Conclusions Based on the data identified by this systematic review, PFM, veneered Zr, and monolithic Zr iFDPs with pontic and iS p Cs showed similarly high short‐term survival rates in the posterior area. Veneered restorations exhibit ceramic chipping more often than monolithic restorations, with the highest fracture rate reported for veneered Zr iFDPs.

Variants of uncertain significance (VUS) in CTLA4 are frequently identified in patients with antibody deficiency or immune dysregulation syndromes including, but not limited to, patients with multi-organ autoimmunity and autoinflammation. However, to ascertain the diagnosis of CTLA4 insufficiency, the functional relevance of each variant needs to be determined. Currently, various assays have been proposed to assess the functionality of CTLA4 VUS, including the analysis of transendocytosis, the biological function of CTLA4 to capture CD80 molecules from antigen presenting cells. Challenges of this assay include weak fluorescence intensity of the internalized ligand, poor reproducibility, and poor performance upon analyzing thawed cells. In addition, the distinction of pathogenic from non-pathogenic variants and from wild-type CTLA4 , and the classification of the different VUS according to its level of CTLA4 dysfunction, would be desirable. We developed a novel CD80-expressing cell line for the evaluation of CD80-transendocytosis and compared it to the published transendocytosis assay. Our approach showed lower inter-assay variability and better robustness regardless the type of starting material (fresh or thawed peripheral mononuclear cells). In addition, receiver operating characteristic analysis showed 100% specificity, avoiding false positive results and allowing for a clear distinction between pathogenic and non-pathogenic variants in CTLA4 -variant carriers. With our transendocytosis assay, we assessed the pathogenicity of 24 distinct CTLA4 variants from patients submitted to our diagnostic unit. Significantly impaired transendocytosis was demonstrated for 17 CTLA4 variants, whereas seven variants tested normal. In conclusion, our upgraded transendocytosis assay allows a reliable assessment of newly identified variants in CTLA4 .

To investigate the intra- and inter-rater reliability of the total radiomics quality score (RQS) and the reproducibility of individual RQS items’ score in a large multireader study. Nine raters with different backgrounds were randomly assigned to three groups based on their proficiency with RQS utilization: Groups 1 and 2 represented the inter-rater reliability groups with or without prior training in RQS, respectively; group 3 represented the intra-rater reliability group. Thirty-three original research papers on radiomics were evaluated by raters of groups 1 and 2. Of the 33 papers, 17 were evaluated twice with an interval of 1 month by raters of group 3. Intraclass coefficient (ICC) for continuous variables, and Fleiss’ and Cohen’s kappa (k) statistics for categorical variables were used. The inter-rater reliability was poor to moderate for total RQS (ICC 0.30–055, p < 0.001) and very low to good for item’s reproducibility (k − 0.12 to 0.75) within groups 1 and 2 for both inexperienced and experienced raters. The intra-rater reliability for total RQS was moderate for the less experienced rater (ICC 0.522, p = 0.009), whereas experienced raters showed excellent intra-rater reliability (ICC 0.91–0.99, p < 0.001) between the first and second read. Intra-rater reliability on RQS items’ score reproducibility was higher and most of the items had moderate to good intra-rater reliability (k − 0.40 to 1). Reproducibility of the total RQS and the score of individual RQS items is low. There is a need for a robust and reproducible assessment method to assess the quality of radiomics research. There is a need for reproducible scoring systems to improve quality of radiomics research and consecutively close the translational gap between research and clinical implementation. • Radiomics quality score has been widely used for the evaluation of radiomics studies. • Although the intra-rater reliability was moderate to excellent, intra- and inter-rater reliability of total score and point-by-point scores were low with radiomics quality score. • A robust, easy-to-use scoring system is needed for the evaluation of radiomics research.

The structure of the vitreous body, its interaction with the retinal surface and tractive alterations of the vitreoretinal interface may play a role in the pathogenesis and the development of age-related macular degeneration (AMD). From clinical trials it can be concluded that posterior vitreous detachment (PVD) or vitreous removal may protect against the development of neovascular AMD. Vitreomacular adhesions may promote neovascular AMD and may have an impact on the efficacy and frequency of intravitreal vascular endothelial growth factor (VEGF) inhibition. Therefore, vitreomacular surgery may be considered as a treatment option in selected cases. Peeling of epimacular membranes and the internal limiting membrane (ILM) may contribute to stabilizing visual acuity and reducing the treatment burden of current intravitreal pharmacotherapy. At present, surgical interventions in AMD are mainly performed in cases of submacular hemorrhage involving the fovea. The treatment is not standardized and consists of liquefaction of the blood using recombinant tissue plasminogen activator (rTPA) and its pneumatic displacement, potentially combined with VEGF inhibition. Other submacular surgical strategies, such as choroidal neovascularization (CNV) extraction, macular translocation or transplantation of retinal pigment epithelium (RPE) are currently limited to selected cases as a salvage treatment; however, the development of these submacular surgical interventions has formed the basis for new approaches in the treatment of dry and neovascular AMD including submacular or intravitreal gene and stem cell therapy.

The success of the visceral leishmaniasis (VL) elimination program largely depends on cost-effective vector control measures. Our goal was to investigate the longevity of the efficacy of insecticidal wall painting (IWP), a new vector control tool, compared with a routine indoor residual spraying (IRS) program for reducing the VL vector density in Bangladesh. This study is the extension of our recent IWP study for VL vector management in Bangladesh, which was undertaken in seven highly VL endemic villages of the Mymensingh district with a 12-month follow-up. In this 24-months follow-up study, we collected sand flies additionally at 15, 18, 21, and 24 months since the interventions from the IWP and control (where the program did routine IRS) clusters to examine the longevity of the efficacy of IWP on sand fly density reduction and mortality. The difference-in-differences regression models were used to estimate the effect of IWP on sand fly reduction against Program IRS. The IWP showed excellent performance in reducing sand fly density and increasing sand fly mortality compared with Program IRS. The effect of IWP for controlling sand flies was statistically significant for up to at least 24 months. The mean female Phlebotomus argentipes density reduction ranged from −56% to −83%, and the P. argentipes sand fly mortality ranged from 81% to 99.5% during the 24-month follow-up period. Considering the duration of the efficacy of IWP for controlling VL vectors, Bangladesh National Kala-azar Elimination Program may consider IWP as the best alternative to IRS for the subsequent phases of the program.

Neutrophils can release neutrophil extracellular traps (NETs) containing DNA fibres and antimicrobial peptides to immobilize invading pathogens. NET formation (NETosis) plays a vital role in inflammation and immune responses. In this study we investigated the impact of surgical trauma on NETosis of neutrophils. Nine patients undergoing “Transcatheter/percutaneous aortic valve implantation” (TAVI/PAVI, mild surgical trauma), and ten undergoing “Aortocoronary bypass” (ACB, severe surgical trauma) were included in our pilot study. Peripheral blood was collected before, end of, and after surgery (24 h and 48 h). Neutrophilic granulocytes were isolated and stimulated in vitro with Phorbol-12-myristate-13-acetate (PMA). NETosis rate was examined by microscopy. In addition, HLA-DR surface expression on circulating monocytes was analysed by flow-cytometry as a prognostic marker of the immune status. Both surgical procedures led to significant down regulation of monocytic HLA-DR surface expression, albeit more pronounced in ACB patients, and there was a similar trend in NETosis regulation over the surgical 24H course. Upon PMA stimulation, no significant difference in NETosis was observed over time in TAVI/PAVI group; however, a decreasing NETosis trend with a significant drop upon ACB surgery was evident. The reduced PMA-induced NETosis in ACB group suggests that the inducibility of neutrophils to form NETs following severe surgical trauma may be compromised. Moreover, the decreased monocytic HLA-DR expression suggests a post-operative immunosuppressed status in all patients, with a bigger impact by ACB, which might be attributed to the extracorporeal circulation or tissue damage occurring during surgery.

Many inborn errors of immunity (IEI) manifest with hallmarks of both immunodeficiency and immune dysregulation due to uncontrolled immune responses and impaired immune homeostasis. A subgroup of these disorders frequently presents with autoimmunity and lymphoproliferation (ALPID phenotype). After the initial description of the genetic basis of autoimmune lymphoproliferative syndrome (ALPS) more than 20 years ago, progress in genetics has helped to identify many more genetic conditions underlying this ALPID phenotype. Among these, the majority is caused by a group of autosomal-dominant conditions including CTLA-4 haploinsufficiency, STAT3 gain-of-function disease, activated PI3 kinase syndrome, and NF-κB1 haploinsufficiency. Even within a defined genetic condition, ALPID patients may present with staggering clinical heterogeneity, which makes diagnosis and management a challenge. In this review, we discuss the pathophysiology, clinical presentation, approaches to diagnosis, and conventional as well as targeted therapy of the most common ALPID conditions.

The substantial reduction of radiation exposure using (ultra-)low dose programs in native computed tomographic imaging has led to considerable changes in imaging diagnostics and treatment planning in urolithiasis in recent years. In addition, especially in Germany, ultrasound diagnostics is highly available in terms of equipment and with increasing expertise. This can largely replace the previous radiation-associated procedures in emergency and follow-up diagnostics, but also in intraoperative imaging, e.g., in percutaneous stone therapy (intraoperative fluoroscopy). This is reflected in the international guidelines, which recommend these two modalities as first-line diagnostics in all areas mentioned. Continuous technical development enables ever higher resolution imaging and thus improved diagnostics with high sensitivity and specificity. This also enables reliable imaging of particularly vulnerable patient groups, such as children or pregnant women. In addition, methods from the field of artificial intelligence (AI; machine learning, deep learning) are increasingly being used for automated stone detection and stone characterization including its composition. Furthermore, AI models can provide prognosis models as well as individually tailored treatment, follow-up, and prophyaxis. This will enable further personalization of diagnostics and therapy in the field of urolithiasis.

The publication of two large randomized studies – the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial and the NRG-GY018 trial – which investigated combining chemotherapy with immunotherapy to treat patients with primary advanced or recurrent endometrial cancer (EC) has transformed the clinical study landscape in terms of first-line therapy for affected patients and has set a new standard of therapy. In the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial, the addition of dostarlimab to standard chemotherapy with carboplatin and paclitaxel resulted in In the NRG-GY018 trial, the addition of pembrolizumab to standard chemotherapy with carboplatin and paclitaxel resulted in As expected, the effect in both trials was much more pronounced in the group of patients with dMMR/MSI-high tumors. According to the assessment of the Uterus Organ Commission of the AGO, all patients with dMMR/MSI-high tumors should receive chemoimmunotherapy and all patients with pMMR/MSI-low tumors who meet the inclusion criteria of the two trials discussed here may have chemoimmunotherapy. For dostarlimab this means: For pembrolizumab this means:

Purpose This study employed machine learning and radiomics to determine whether postoperative pancreatic fistulas (POPF) and perioperative drain amylase dynamics can be predicted prior to pancreaticoduodenectomy by evaluating the radiologic appearance of the pancreatic tissue. Methods 68 patients were included. Radiomic features of the pancreas were extracted from the arterial phase of computed tomography (CT) at a 1 mm slice thickness for each patient. the Radiomic features with highest correlation with POPF for our models, controlling for autocorrelation and applying Bonferroni correction for P-values were selected. For amylase prediction model (APM), radiomic features were correlated with postoperative maximum drain amylase levels at a cut-off of 1000U/l. ROC analysis was performed for evaluation of the resulting prediction models. Results POPF prediction model (PPM) showed an area under the curve (AUC) of 0.897 (confidence interval (CI) = 82.3–97.1%) in the cohort. The AUC of PPM was higher than that for Roberts’ score, but the difference was not statistically significant. An attempt to predict postoperative amylase dynamics in the drainage fluid achieved an AUC of 0.936 (CI = 88%-99.1%). Conclusions Preoperative prediction of POPF and drain amylase dynamics using radiomics showed promising results. Both models offer new approaches to the clinical management of POPF.

Recent advancements in machine learning achieved by Deep Neural Networks (DNNs) have been significant. While demonstrating high accuracy, DNNs are associated with a huge number of parameters and computations, which leads to high memory usage and energy consumption. As a result, deploying DNNs on devices with constrained hardware resources poses significant challenges. To overcome this, various compression techniques have been widely employed to optimize DNN accelerators. A promising approach is quantization, in which the full-precision values are stored in low bit-width precision. Quantization not only reduces memory requirements but also replaces high-cost operations with low-cost ones. DNN quantization offers flexibility and efficiency in hardware design, making it a widely adopted technique in various methods. Since quantization has been extensively utilized in previous works, there is a need for an integrated report that provides an understanding, analysis, and comparison of different quantization approaches. Consequently, we present a comprehensive survey of quantization concepts and methods, with a focus on image classification. We describe clustering-based quantization methods and explore the use of a scale factor parameter for approximating full-precision values. Moreover, we thoroughly review the training of a quantized DNN, including the use of a straight-through estimator and quantized regularization. We explain the replacement of floating-point operations with low-cost bitwise operations in a quantized DNN and the sensitivity of different layers in quantization. Furthermore, we highlight the evaluation metrics for quantized methods and important benchmarks in the image classification task. We also present the accuracy of the state-of-the-art methods on CIFAR-10 and ImageNet. This paper attempts to make the readers familiar with the basic and advanced concepts of quantization, introduce important works in DNN quantization, and highlight challenges for future research in this field.

We sought to devise a rational, systematic approach for defining/grouping survival motor neuron-targeted disease-modifying treatment (DMT) scenarios. The proposed classification is primarily based on a two-part differentiation: initial DMT, and persistence/discontinuation of subsequent DMT(s). Treatment categories were identified: monotherapy add-on, transient add-on, combination with onasemnogene abeparvovec, bridging to onasemnogene abeparvovec, and switching to onasemnogene abeparvovec. We validated this approach by applying the classification to the 443 patients currently in the RESTORE registry and explored the demographics of these different groups of patients. This work forms the basis to explore the safety and efficacy profile of the different combinations of DMT in SMA.

BACKGROUND Studies into the genetics of peripheral nerve tumors have been focused on their association with known gene mutations and syndromes as well as on the tumor microenvironment of malignant peripheral nerve sheath tumors. Still, not many advances have been made into clarifying the structure and diverse pathophysiology of these tumors. Here we present spatially resolved transcriptomic profiling of benign and malignant entities and describe the topographical architecture of the neoplastic and microenvironmental diversity. MATERIAL AND METHODS We employed spatially resolved transcriptomics using the 10X Visium technology from paraffine embedded specimens. We included hybrid peripheral nerve sheath tumors (HPNSTs) plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNST). Computational analysis was employed by the SPATA2 toolbox. Transcriptomic niches were identified by graph-based spatial clustering. Correlation of histomorphological features and transcriptomic programs was performed by a co-expression network-based analysis. RESULTS We identified hub genes associated with neurofibroma and schwannoma histopathology across primary pathologies and discovered that neurofibroma regions of HPNSTs exhibited unique transcriptional programs marked by a significant higher local accumulation of bone-derived macrophages and lymphoid cells compared to primary neurofibromas. A novel marker, Apolipoprotein D (APOD), was found to accurately identify neurofibroma subregions in HPNSTs, which was confirmed by immunostaining in a control cohort. In MPNSTs, we observed a high grade of inter- and intrapatient heterogeneity driven by unique transcriptional niches and genetic variability. Subsequent pathway analysis revealed distinct oncogenic signaling driver across regional niches along with variance in immune infiltration. Our findings highlight the disbalance between histological annotation and actual tumor cell abundance in MPNSTs indicated by inferred copy number alterations. CONCLUSION Our integrated analysis pipeline revealed distinct transcriptional signatures and cellular interactions within benign PNSTs, including neurofibromas and hybrid peripheral nerve sheath tumors (HPNSTs) and sought to expose the tumor heterogeneity of MPNST and identify various cancer niches. Our study underscores the potential of spatially resolved transcriptomics as a powerful tool for advancing our understanding of PNST biology, and ultimately improving diagnosis, prognosis, and treatment strategies.

BACKGROUND The leading edge of glioblastomas is characterized by the crowding of neoplastic cells around neurons and inside the perivascular space, a phenomenon known as satellitosis. Recent research has focused on the interaction between glioblastoma cells and neuronal networks, but the specific cells contributing to perivascular satellitosis have not been comprehensively studied. MATERIAL AND METHODS To address this gap, we conducted single-nucleus RNA sequencing on glioblastoma samples, dissecting the leptomeninges and tumor core from freshly resected tissue. As the brain parenchyma and perivascular space cannot be easily separated, we sampled tumor cells from the leptomeninges, the outer limit of the perivascular space. This approach harnesses the fact that the subarachnoid and perivascular spaces are directly connected. Thus, we could isolate perivascularly located tumor cells. RESULTS Our analyses revealed distinct transcriptional signatures between tumor cells from the leptomeninges and those from the tumor core. Tumor core-associated cells showed transcriptional programs related to hypoxia and collagen expression, while leptomeningeal tumor cells displayed programs related to axonal guidance, synaptic function, and extracellular matrix expression. Interestingly, there was significant overlap with previously published gene expression programs found in tumor cells integrating into neuronal circuits. Cell-cell interaction analysis identified interaction between tumor cells and the resident cell types of the perivascular space, including fibroblasts, perivascular macrophages and lymphocytes. CONCLUSION Our study provides a robust methodology for high-dimensional analysis of glioblastoma cells spreading through the perivascular space in human patients. Using this methodology we shed light on the biological processes of perivascular satellitosis and the spread of glioblastoma cells via pre-existing anatomical niches. Due to the distinct cellular composition of the perivascular space, the biology of satellitosis is distinct from the processes in the parenchyma. These findings have important implications for the development of targeted molecular therapies for glioblastomas.

Purpose Low-risk early breast cancer rarely leads to the development of metastatic disease, and in these patients, additional imaging test is controversial. The aim of our study was to evaluate the conventional staging procedures in a bicentric German series of low-risk breast carcinoma patients. Methods Retrospective evaluation of all patients diagnosed with early, low-risk breast cancer at Saarland University Hospital and Freiburg University Hospital in 2017 was performed. Clinical patient characteristics, the number and type of additional imaging examinations, follow-up examinations, and results were evaluated. The detection rate of metastases and the rate of false-positive findings were analyzed. Results A total of 203 patients were included, with all patients received at least one additional imaging test. Initially, a total of 562 additional imaging examinations were performed: 166 chest X-rays, 169 upper abdominal ultrasounds, 199 bone scans, 27 computer tomographies (CT) chest and abdomen, and 1 CT abdomen. 6.8% of patients had abnormal findings reported, requiring 38 additional imaging examinations. One patient (0.5%) was found to have bone metastases. The rate of false-positive findings in the performed additional imaging procedures was 6.6%. Conclusion Metastatic disease was detected in one of 203 patients with low-risk early breast cancer. A total of 562 examinations and additional 38 follow-up examinations were performed without detection of metastasis (this corresponds to approximately 3 examinations/patient). The rate of false-positive findings was 6.6%. The performance of additional imaging procedures for detection of distant metastases should be critically reconsidered in patients with low-risk early breast cancer.