Osteomyelitis (OM) remains one of the most feared complications in bone surgery and trauma. Its diagnosis remains a major challenge due to lack of guidelines. The aim of this study was to prospectively analyze the value of the most common and available diagnostic tools and to establish an OM score to derive treatment recommendations. All patients with suspected OM were included in a prospective pilot study. All patients underwent blood sampling for C-reactive protein and white blood cell count analysis. Magnetic resonance imaging (MRI), and microbiologic and histopathologic samples, were taken from representative sites of initial debridement. All patients were treated according to their OM test results and followed for at least one year. Subsequently, the value of individual or combined diagnostic tools was analyzed in patients with confirmed OM and in patients in whom OM was ruled out. Based on these findings, an OM score was developed that included MRI, microbiology, and histopathology. The score identified all control patients and all but one OM patient, resulting in a correct diagnosis of 93.3%, which was validated in a second independent larger cohort. This was the first study to analyze the value of the most commonly used tools to diagnose OM. The proposed OM score provides a simple scoring system to safely interpret test results with high accuracy.
Background: Osteomyelitis, particularly affecting the lower extremities, is a serious and increasingly common complication. Accurate diagnosis is essential for successful treatment, yet standardized evidence-based protocols are lacking and diagnostic knowledge remains limited. This study aimed to identify characteristic histological and MRI findings in osteomyelitis to support diagnostic accuracy and guide treatment decisions. Methods: In a prospective case-control pilot study conducted from February 2020 to January 2021, all patients with suspected osteomyelitis of the lower limbs were included. Each underwent contrast-enhanced MRI and sampling for microbiological and histological analysis. Findings from five confirmed osteomyelitis cases were compared to five controls where osteomyelitis was ruled out. Results: All osteomyelitis cases showed typical MRI signs, including contrast-enhancing bone edema. Two had early, and two had pronounced intramedullary abscesses. In three controls, contrast-enhancing edema was limited to soft tissue; two showed mild adjacent bone edema. Histologically, all osteomyelitis samples revealed bone fragmentation and inflammatory cell infiltration—absent in controls. Additionally, four showed medullary fibrosis and one fibrin deposits. Conclusions: A comprehensive understanding of both histological and radiological findings is key to effective osteomyelitis treatment. This pilot study is the first to systematically compare MRI and histology findings side by side, offering valuable insights that may enhance diagnostic precision and support evidence-based treatment decisions.
Background: The diagnostic work-up of small peripheral pulmonary nodules (PPNs) is becoming increasingly important, especially in light of the upcoming lung cancer screening programs and recommendations in practice. The systematic clinical introduction of the ION robotic-assisted navigational bronchoscopy (RNB) system represents a significant innovation in Germany, whereas clinical experience in the United States has already yielded promising results. The objective of this study is to present the outcomes of the first 50 patients examined with the ION system at our institutions. Materials and Methods: This is a retrospective, single-center analysis. We included the first 50 consecutive patients who underwent diagnostic evaluation of pulmonary nodules using the ION-RNB system, either in the Department of Thoracic Surgery or the Department of Pulmonology. Results: A total of 50 patients were evaluated, including 24 from the Department of Thoracic Surgery and 26 from the Department of Pulmonology. The pulmonary nodules were found in the peripheral third of the lung in 74% of cases, in the middle third in 18% of cases, and in the central third in 8% of cases. The mean lesion size was 1.64 cm (±0.91 cm). In all, 84% of the nodules were solid, 4% were subsolid, and 12% presented as ground-glass opacities (GGOs). Cone beam computed tomography (CBCT) was used to confirm tool-in-lesion position in 68% of cases compared to C-arm fluoroscopy in 32%. Additionally, radial endobronchial ultrasound (rEBUS) was applied in 30% of procedures. The overall diagnostic yield, independent of imaging modality or histological processing method, was 78%. When CBCT and formalin-fixed paraffin-embedded (FFPE) histological analysis were utilized, the diagnostic yield exceeded 90%. Conclusions: Initial clinical experience with the ION-RNB system in Germany shows encouraging results. The high diagnostic accuracy underlines the system’s potential for evaluating peripheral pulmonary lesions precisely. The use of advanced imaging techniques, particularly CBCT, and the choice of histopathological processing methods are critical variables in optimizing patient-centered diagnostic pathways. Further prospective studies are warranted to assess the long-term clinical utility of robotic-assisted bronchoscopy in diverse clinical settings.
Precise control of oncogene expression is crucial for advancing tumor biology research and therapeutic testing. To address the limitations of current systems, we developed a novel, tightly regulated, genome-integrable inducible expression platform based on an optimized cumate gene-switch system. By engineering a KRAB-fused, NLS-enhanced CymR repressor (CSwitch-Silencer), a CpG-free hybrid promoter, and a PiggyBac-based integration strategy, insulated by matrix attachment regions, we achieved robust, reversible, and dose-dependent transgene expression with basal activity below detection. With the receptor tyrosine kinase cMET as a model, we generated CRISPR–Cas9-derived cMET -deficient A549 cells and established inducible lines expressing wild-type and clinically relevant variants, including exon 14 skipping and H1094Y. The system enabled precise tuning of expression levels and faithful recapitulation of downstream signaling and phenotypic responses. Pharmacological profiling revealed variant-specific sensitivities to clinically relevant MET inhibitors, with the H1094Y mutation exhibiting increased sensitivity to the type II inhibitor cabozantinib, while exon 14 skipping conferred reduced sensitivity. These effects were consistent across biochemical and functional assays, including receptor activation and cell migration. Collectively, this platform provides a versatile and scalable approach for modeling oncogene function and drug response in a controlled genetic context. Its tight regulation, modular design, and stable genomic integration make it broadly applicable for functional characterization of cancer-associated variants and for preclinical evaluation of targeted therapies.