Nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is key in maintaining redox homeostasis and the pathogenesis of osteoarthritis (OA) involves oxidative distress. We thus investigated whether Nrf2/ARE signaling may control expression of key chondrogenic differentiation and hyaline cartilage maintenance factor SOX9.

In human C-28/I2 chondrocytes SOX9 expression was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap “n” collar homology-associated protein 1 (Keap1). Putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays to verify whether Nrf2 transcriptionally regulates SOX9. SOX9 promoter activity without and with Nrf2-inducer methysticin were analyzed. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Data were analyzed by one-way ANOVA, a Student's t-test, or Wilcoxon rank-sum test, according to the normal distribution. Statistical significance was set to p < 0.05.

While Keap1-specific RNAi increased SOX9 expression, Nrf2-specific RNAi significantly decreased it. Putative ARE sites (ARE₁, ARE₂) were identified in the SOX9 promoter region. ARE₂ mutagenesis significantly reduced SOX9 promoter activity, while truncation of ARE₁ did not. A functional ARE₂ site was thus essential for methysticin-mediated induction of SOX9 promoter activity. Knee cartilage of young Nrf2-knockout mice further revealed significantly fewer Sox9-positive chondrocytes as compared to old Nrf2-knockout animals, which further showed thinner cartilage and more severe cartilage erosion.

Our data suggest that SOX9 expression in articular cartilage is directly Nrf2-dependent and that pharmacological Nrf2 activation may hold potential to diminish age-dependent osteoarthritic changes in knee cartilage through improving protective SOX9 expression.

Helical plates potentially bypass the medial neurovascular structures of the thigh. Recently, two plate designs (90°- and 180°-helix) proved similar biomechanically behaviour compared to straight plates. Aims of this study were: (1) Feasibility of MIPO-technique with 90°- and 180°-helical plates on the femur, (2) Assessment of distances to adjacent anatomical structures at risk, (3) Comparison of these distances to using medial straight plates instead, (4) Correlation of measurements performed in anatomic dissection with CT-angiography.

MIPO was performed in ten cadaveric femoral pairs using either a 90°-helical 14-hole-LCP (Group1) or a 180°-helical 15-hole-LCP-DF (Group2). CT angiography was used to evaluate the distances between the plates and the femoral arteries as well as the distances between the plates and the perforators. Subsequently, the specimens were dissected, and the distances were determined again manually. Finally, all helical plates were removed, and all measurements were repeated after application of straight medial plates (Group3).

Closest overall distances between plates and femoral arteries were 15 mm (11 − 19 mm) in Group1, 22 mm (15 − 24 mm) in Group2 and 6 mm (1 − 8 mm) in Group3 with a significant difference between Group1 and Group3 (p < 0.001). Distances to the nearest perforators were 24 mm (15 − 32 mm) in Group1 and 2 mm (1 − 4 mm) in Group2. Measurement techniques (visual after surgery and CT-angiography) demonstrated a strong correlation of r² = 0.972 (p < 0.01).

MIPO with 90°- and 180°-helical plates is feasible and safe. Attention must be paid to the medial neurovascular structures with 90°-helical implants and to the proximal perforators with 180°-helical implants. Helical implants can avoid medial neurovascular structures compared to straight plates although care must be taken during their distal insertion. Measurements during anatomical dissection correlate with CT-angiography.

Proximal humeral shaft fractures are commonly treated with long straight locking plates endangering the radial nerve distally. The aim of this study was to investigate the biomechanical competence in a human cadaveric bone model of 90°-helical PHILOS plates versus conventional straight PHILOS plates in proximal third comminuted humeral shaft fractures.

Eight pairs of humeral cadaveric humeri were instrumented using either a long 90°-helical plate (group1) or a straight long PHILOS plate (group2). An unstable proximal humeral shaft fracture was simulated by means of an osteotomy maintaining a gap of 5cm. All specimens were tested under quasi-static loading in axial compression, internal and external rotation as well as bending in 4 directions. Subsequently, progressively increasing internal rotational loading until failure was applied and interfragmentary movements were monitored by means of optical motion tracking.

Flexion/extension deformation (°) in group1 was (2.00±1.77) and (0.88±1.12) in group2, p=0.003. Varus/valgus deformation (°) was (6.14±1.58) in group1 and (6.16±0.73) in group2, p=0.976. Shear (mm) and displacement (°) under torsional load were (1.40±0.63 and 8.96±0.46) in group1 and (1.12±0.61 and 9.02±0.48) in group2, p≥0.390. However, during cyclic testing shear and torsional displacements and torsion were both significantly higher in group 1, p≤0.038. Cycles to catastrophic failure were (9960±1967) in group1 and (9234±1566) in group2, p=0.24.

Although 90°-helical plating was associated with improved resistance against varus/valgus deformation, it demonstrated lower resistance to flexion/extension and internal rotation as well as higher flexion/extension, torsional and shear movements compared to straight plates. From a biomechanical perspective, 90°-helical plates performed inferior compared to straight plates and alternative helical plate designs with lower twist should be investigated in future paired cadaveric studies.

Fluoroscopic guidance is common in interventional pain procedures. In spine surgery, injections are used for differential diagnosis and determination of indication for surgical treatment as well. Fluoroscopy ensures correct needle placement and accurate delivery of the drug. Also, exact documentation of the intervention performed is possible. However, besides the patient, interventional pain physicians, surgeons and other medical staff are chronically exposed to low dose scatter radiation. The long-term adverse consequences of low dose radiation exposure to the medical staff are still unclear. Especially in university hospital settings, where education of trainees is performed, fluoroscopy time and total radiation exposure are significantly higher than in private practice settings. It remains a challenge for university hospitals to reduce the fluoroscopic time while maintaining the quality of education.

Multiple approaches have been made to reduce radiation exposure in fluoroscopy, including the wide spread use of pulsed fluoroscopy, or rarely used techniques like laser guided needle placement systems. The Zero-Dose-C-Arm-Navigation (ZDCAN) allows an optimal positioning of the c-arm without exposure to radiation. For training purposes, relevant anatomical structures can be highlighted for each interventional procedure, so injection needles can be best positioned next to the target area.

The Zero-Dose-C-Arm-Navigation (ZDCAN) module was developed to display a radiation free preview of the expected fluoroscopic image of the spine. Using an optical tracking system and a registered 3D-spine model, the expected x-ray image is displayed in real-time as a projection of the model. Additionally, selected anatomical structures including nerve roots, facet joints, vertebral discs and the epidural space, can be displayed. A seamless integration of the ZDCAN in a c-arm system already used in clinical practice for years could be achieved. For easy use, a tool was developed allowing the admission and use of regular single-use syringes and spinal needles. Accordingly, these can be used as pointers in the sterile area, a sterilization of the whole tool after every single injection is not required. We evaluated the efficiency and accuracy of this procedure compared to conventional fluoroscopically guided interventional procedures. In sawbones of the lumbar spine, facet joint injections (N = 50), perineural injections (N = 46) and epidural injections (N = 20) were performed.

Highlighting the target area in the radiation free preview model, an optimal positioning of the c-arm could be achieved even by unskilled medical staff. The desired anatomical structures could be identified easily in the x-rays taken, as they were displayed in the 3D model aside. As already seen evaluating a previous version of the ZDCAN module for the lower limb, the total number of x-ray images taken could be reduced significantly. Compared to the conventional group, the number of x-ray images required for facet joint injections could be reduced from 12.5 (±1.1) to 5.7 (±1.1), from 5.4 (±1.8) to 3.8 (±1.3) for perineural injections and from 4.1 (±0.9) to 2.1 (±0.3) for epidural injections. Total radiation time was reduced accordingly. Likewise, the mean time needed for the interventional procedure could be reduced from 168.3 s (±19.1) to 131.4 s (±16.8) for facet joint injections, was unchanged from 97.7 s (±26.0) to 104.7 s (±31.0) for perineural injections and from 60 s (±14.9) to 52 s (±7.1) for epidural injections.

The ZDCAN is a powerful tool advancing conventional fluoroscopy to another level. Using the radiation free preview model, the c-arm can easily be positioned to show the desired area. The accentuated display of the target structures in the preview model makes the introduction to fluoroscopy guided interventional procedures easier. This feature might reduce the learning curve to achieve better clinical results with lower radiation dose exposure. Thus, the ZDCAN can be a tool to improve education in university hospital settings for physicians as well as for medical staff while reducing radiation dose exposure in general use.