Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II)
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- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (22)
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Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse
(2022)
Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{−/−}\) and wild-type mice. In RIM1α\(^{−/−}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0–2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{−/−}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.
Background
Avascular necrosis of the humeral head after proximal humeral fracture i.e. type 1 fracture sequelae (FS) according to the Boileau classification is a rare, often painful condition and treatment still remains a challenge. This study evaluates the treatment of FS type 1 with anatomic and reverse shoulder arthroplasty and a new subclassification is proposed.
Methods
This single-center, retrospective, comparative study, included all consecutive patients with a proximal humeral FS type 1 treated surgically in a four-year period. All patients were classified according to the proposed 3 different subtypes.
Constant score (CS), Quick DASH score, subjective shoulder value (SSV) as well as revision and complication rate were analyzed. In the preoperative radiographs the acromio-humeral interval (AHI) and greater tuberosity resorption were examined.
Results
Of 27 with a FS type 1, 17 patients (63%) with a mean age of 64 ± 11 years were available for follow-up at 24 ± 10 months. 7 patients were treated with anatomic and 10 with reverse shoulder arthroplasty. CS improved significantly from 16 ± 7 points to 61 ± 19 points (p < 0.0001). At final follow-up the mean Quick DASH Score was 21 ± 21 and the mean SSV was 73 ± 21 points. The mean preoperative AHI was 9 ± 3 mm, however, 8 cases presented an AHI < 7 mm. 4 cases had complete greater tuberosity resorption.
The complication and revision rate was 19%; implant survival was 88%.
Conclusion
By using the adequate surgical technique good clinical short-term results with a relatively low complication rate can be achieved in FS type 1. The Boileau classification should be extended for fracture sequelae type 1 and the general recommendation for treatment with hemiarthroplasty or total shoulder arthroplasty has to be relativized. Special attention should be paid to a decreased AHI and/or resorption of the greater tuberosity as indirect signs for dysfunction of the rotator cuff. To facilitate the choice of the adequate prosthetic treatment method the suggested subclassification system should be applied.
Introduction
Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release.
Methods
We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system.
Results and discussion
Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels.
The calcaneal beak fracture is a rare avulsion fracture of the tuber calcanei characterized by a solid bony fragment at the Achilles tendon insertion. Treatment usually requires osteosynthesis. However, lack of biomechanical understanding of the ideal fixation technique persists. A beak fracture was simulated in synthetic bones and assigned to five different groups of fixation: A) 6.5-mm partial threaded cannulated screws, B) 4.0-mm partial threaded cannulated screws, C) 5.0-mm headless cannulated compression screws, D) 2.3-mm locking plate, and E) 2.8-mm locking plate. Different traction force levels were applied through an Achilles tendon surrogate in a material-testing machine on all stabilized synthetic bones. Outcome measures were peak-to-peak displacement, total displacement, plastic deformation, stiffness, visual-fracture-line displacement, and mode of implant failure. The 2.3- and 2.8-mm plating groups showed a high drop-out rate at 100 N tension force and failed under higher tension levels of 200 N. The fracture fixation using 4.0-mm partial threaded screws showed a significantly higher repair strength and was able to withhold cyclic loading up to 300 N. The lowest peak-to-peak displacement and the highest load-to-failure and stiffness were provided by fracture fixation using 6.5-mm partial threaded cannulated screws or 5.0-mm headless cannulated compression screws. As anticipated, large 6.5-mm screw diameters provide the best biomechanical fixation. Surprisingly, the 5.0-mm headless cannulated compression screws yield reliable stability despite the absent screw head and washer. When such large screws cannot be applied, 4.0-mm screws also allow reasonable fixation strength. Plate fixation should be implemented with precaution and in combination with a restrictive postoperative motion protocol. Finally, clinical cases about the surgical application and recovery are included.
Background
Traumatic separation of the pubic symphysis can destabilize the pelvis and require surgical fixation to reduce symphyseal gapping. The traditional approach involves open reduction and the implantation of a steel symphyseal plate (SP) on the pubic bone to hold the reposition. Despite its widespread use, SP-fixation is often associated with implant failure caused by screw loosening or breakage.
Methods
To address the need for a more reliable surgical intervention, we developed and tested two titanium cable-clamp implants. The cable served as tensioning device while the clamp secured the cable to the bone. The first implant design included a steel cable anterior to the pubic symphysis to simplify its placement outside the pelvis, and the second design included a cable encircling the pubic symphysis to stabilize the anterior pelvic ring. Using highly reproducible synthetic bone models and a limited number of cadaver specimens, we performed a comprehensive biomechanical study of implant stability and evaluated surgical feasibility.
Results
We were able to demonstrate that the cable-clamp implants provide stability equivalent to that of a traditional SP-fixation but without the same risks of implant failure. We also provide detailed ex vivo evaluations of the safety and feasibility of a trans-obturator surgical approach required for those kind of fixation.
Conclusion
We propose that the developed cable-clamp fixation devices may be of clinical value in treating pubic symphysis separation.
Background
Morphology and glenoid involvement determine the necessity of surgical management in scapula fractures. While being present in only a small share of patients with shoulder trauma, numerous classification systems have been in use over the years for categorization of scapula fractures. The purpose of this study was to evaluate the established AO/OTA classification in comparison to the classification system of Euler and Rüedi (ER) with regard to interobserver reliability and confidence in clinical practice.
Methods
Based on CT imaging, 149 patients with scapula fractures were retrospectively categorized by two trauma surgeons and two radiologists using the classification systems of ER and AO/OTA. To measure the interrater reliability, Fleiss kappa (κ) was calculated independently for both fracture classifications. Rater confidence was stated subjectively on a five-point scale and compared with Wilcoxon signed rank tests. Additionally, we computed the intraclass correlation coefficient (ICC) based on absolute agreement in a two-way random effects model to assess the diagnostic confidence agreement between observers.
Results
In scapula fractures involving the glenoid fossa, interrater reliability was substantial (κ = 0.722; 95% confidence interval [CI] 0.676–0.769) for the AO/OTA classification in contrast to moderate agreement (κ = 0.579; 95% CI 0.525–0.634) for the ER classification system. Diagnostic confidence for intra-articular fracture patterns was superior using the AO/OTA classification compared to ER (p < 0.001) with higher confidence agreement (ICC: 0.882 versus 0.831). For extra-articular fractures, ER (κ = 0.817; 95% CI 0.771–0.863) provided better interrater reliability compared to AO/OTA (κ = 0.734; 95% CI 0.692–0.776) with higher diagnostic confidence (p < 0.001) and superior agreement between confidence ratings (ICC: 0.881 versus 0.912).
Conclusions
The AO/OTA classification is most suitable to categorize intra-articular scapula fractures with glenoid involvement, whereas the classification system of Euler and Rüedi appears to be superior in extra-articular injury patterns with fractures involving only the scapula body, spine, acromion and coracoid process.
Older patients sustaining tibial head depression fractures often cannot follow the post-operative rehabilitation protocols with partial weight-bearing of the affected limb, leading to osteosynthesis failure, cartilage step-off and arthritis development. Therefore, the aim of this study was to analyse the biomechanical performance of different types of osteosyntheses alone and in combination with bone cement simulating cyclically high loading conditions of tibial head depression fractures. Lateral tibial head depression fractures (AO: 41-B2.2; Schatzker type III) were created in synthetic bones and stabilized using three different osteosyntheses alone and in combination with a commonly used bone cement (chronOS™): 2 screws, 4 screws in the jail technique and a lateral angle-stable buttress plate. After fixation, the lateral tibial plateau was axially loaded in two, from each other independent testing series: In the first test protocol, 5000 cycles with 500 N and in the end load-to-failure tests were performed. In the second test protocol, the cyclic loading was increased to 1000 N. Parameters of interest were the displacement of the articular fracture fragment, the stiffness and the maximum load. The osteosyntheses revealed a higher stiffness in combination with bone cement compared to the same type of osteosynthesis alone (e.g., 500 N level: 2 screws 383 ± 43 N/mm vs. 2 screws + chronOs 520 ± 108 N/mm, increase by 36%, p < 0.01; 4 screws 368 ± 97 N/mm vs. 4 screws + chronOS 516 ± 109 N/mm, increase by 40%, p < 0.01; plate: 509 ± 73 N/mm vs. plate + chronOs 792 ± 150 N/mm, increase by 56%, p < 0.01). Bone cement reduced the displacement of the plate significantly (500 N level: plate: 8.9 ± 2.8 mm vs. plate + chronOs: 3.1 ± 1.4 mm, reduction by 65%, p < 0.01; 1000 N level: 16.9 ± 3.6 mm vs 5.6 ± 1.3 mm, reduction by 67%, p < 0.01). Thus, the highest stiffness and lowest displacement values were found when using the plate with bone cement in both loading conditions (500 N level: 2 screws + chronOs 3.7 ± 1.3 mm, 4 screws + chronOs 6.2 ± 2.4 mm; 1000 N level: 2 screws + chronOs 6.5 ± 1.2 mm, 4 screws + chronOs 5.7 ± 0.8 mm). From a biomechanical perspective, plate osteosynthesis of tibial head depression fractures should always be combined with bone cement, provides higher stability than 2-screw and 4-screw fixation and is a valid treatment option in cases where extraordinary stability is required.
In 3D bioprinting for cartilage regeneration, bioinks that support chondrogenic development are of key importance. Growth factors covalently bound in non-printable hydrogels have been shown to effectively promote chondrogenesis. However, studies that investigate the functionality of tethered growth factors within 3D printable bioinks are still lacking. Therefore, in this study, we established a dual-stage crosslinked hyaluronic acid-based bioink that enabled covalent tethering of transforming growth factor-beta 1 (TGF-β1). Bone marrow-derived mesenchymal stromal cells (MSCs) were cultured over three weeks in vitro, and chondrogenic differentiation of MSCs within bioink constructs with tethered TGF-β1 was markedly enhanced, as compared to constructs with non-covalently incorporated TGF-β1. This was substantiated with regard to early TGF-β1 signaling, chondrogenic gene expression, qualitative and quantitative ECM deposition and distribution, and resulting construct stiffness. Furthermore, it was successfully demonstrated, in a comparative analysis of cast and printed bioinks, that covalently tethered TGF-β1 maintained its functionality after 3D printing. Taken together, the presented ink composition enabled the generation of high-quality cartilaginous tissues without the need for continuous exogenous growth factor supply and, thus, bears great potential for future investigation towards cartilage regeneration. Furthermore, growth factor tethering within bioinks, potentially leading to superior tissue development, may also be explored for other biofabrication applications.
Bone marrow lesions (BML) represent areas of deteriorated bone structure and metabolism characterized by pronounced water‐equivalent signaling within the trabecular bone on magnetic resonance imaging (MRI). BML are associated with repair mechanisms subsequent to various clinical conditions associated with inflammatory and non‐inflammatory injury to the bone. There is no approved treatment for this condition. Bisphosphonates are known to improve bone stability in osteoporosis and other bone disorders and have been used off‐label to treat BML. A randomized, triple‐blind, placebo‐controlled phase III trial was conducted to assess efficacy and safety of single‐dose zoledronic acid (ZOL) 5 mg iv with vitamin D 1000 IU/d as opposed to placebo with vitamin D 1000 IU/d in 48 patients (randomized 2:1) with BML. Primary efficacy endpoint was reduction of edema volume 6 weeks after treatment as assessed by MRI. After treatment, mean BML volume decreased by 64.53% (±41.92%) in patients receiving zoledronic acid and increased by 14.43% (±150.46%) in the placebo group (p = 0.007). A decrease in BML volume was observed in 76.5% of patients receiving ZOL and in 50% of the patients receiving placebo. Pain level (visual analogue scale [VAS]) and all categories of the pain disability index (PDI) improved with ZOL versus placebo after 6 weeks but reconciled after 6 additional weeks of follow‐up. Six serious adverse events occurred in 5 patients, none of which were classified as related to the study drug. No cases of osteonecrosis or fractures occurred. Therefore, single‐dose zoledronic acid 5 mg iv together with vitamin D may enhance resolution of bone marrow lesions over 6 weeks along with reduction of pain compared with vitamin D supplementation only.
Biomechanische vergleichende Arbeit von drei Osteosynthesesystemen für die Versorgung einer
Klavikulaschaftfraktur. Die drei Osteosyntheseplatten wurden auf insgesamt 24 osteotomierte
Kunstklavikulae der Firma Sawbone angebracht. Die Steifigkeit der Klavikulaosteosynthesen wurden
durch eine zyklische torsionale Belastung, eine zyklische axiale Stauchung und eine zyklische
freischwingende Biegung im 3-Punkt-Biegeversuch untersucht. Dazu wurde die maximale Belastbarkeit
der Osteosynthesen mittels Load-to-failure Testung ermittelt. Die Daten wurden mittels dem Programm
TestXpert aufgezeichnet und statistisch ausgewertet. Außerdem wurde jeder Versuch graphisch mittels
Spannung-Dehnungs Diagramm dargestellt und miteinander verglichen.