Importance of locking plate positioning in proximal humeral fractures as predicted by computer simulations

Multifragmented proximal humeral fractures frequently require operative fixation. The locking plates commonly used are often placed relative to the greater tuberosity, however no quantitative data exists regarding the effect of positional changes. The aim of the study was to establish the effects from variations in proximal‐distal PHILOS humeral plate positioning on predicted fixation failure risk. Twenty‐one left‐sided low‐density virtual humeri models were created with a simulation framework from CT data of elderly donors and osteotomized to mimic an unstable three‐part malreduced AO/OTA 11‐B3.2 fracture with medial comminution. A PHILOS plate with either four or six proximal screws was used for fixation. Both configurations were modelled with plate repositioning 2 and 4 mm distally and proximally to its baseline position. Applying a validated computational model, three physiological loading situations were simulated and fixation failure predicted using average strain around the proximal screws – an outcome established as a surrogate for cycles to failure. Varying the craniocaudal plate position affected the peri‐implant strain for both four and six‐screw configurations. Even though significant changes were seen only in the latter, all tests suggested that more proximal plate positioning results in decreased peri‐screw strains whereas distalizing creates increases in strain. These results suggest that even a small distal PHILOS plate malpositioning may reduce fixation stability. Plate distalization increases the probability of being unable to insert all screws within the humeral head, which dramatically increases the forces acting on the remaining screws. Proximal plate shifting may be beneficial, especially for constructs employing calcar screws.This article is protected by copyright. All rights reserve

Importance of locking plate positioning in proximal humeral fractures as predicted by computer simulations

Multifragmented proximal humeral fractures frequently require operative fixation. The locking plates commonly used are often placed relative to the greater tuberosity, however no quantitative data exists regarding the effect of positional changes. The aim of the study was to establish the effects from variations in proximal‐distal PHILOS humeral plate positioning on predicted fixation failure risk. Twenty‐one left‐sided low‐density virtual humeri models were created with a simulation framework from CT data of elderly donors and osteotomized to mimic an unstable three‐part malreduced AO/OTA 11‐B3.2 fracture with medial comminution. A PHILOS plate with either four or six proximal screws was used for fixation. Both configurations were modelled with plate repositioning 2 and 4 mm distally and proximally to its baseline position. Applying a validated computational model, three physiological loading situations were simulated and fixation failure predicted using average strain around the proximal screws – an outcome established as a surrogate for cycles to failure. Varying the craniocaudal plate position affected the peri‐implant strain for both four and six‐screw configurations. Even though significant changes were seen only in the latter, all tests suggested that more proximal plate positioning results in decreased peri‐screw strains whereas distalizing creates increases in strain. These results suggest that even a small distal PHILOS plate malpositioning may reduce fixation stability. Plate distalization increases the probability of being unable to insert all screws within the humeral head, which dramatically increases the forces acting on the remaining screws. Proximal plate shifting may be beneficial, especially for constructs employing calcar screws.This article is protected by copyright. All rights reserve

Screw configuration in proximal humerus plating has a significant impact on fixation failure risk predicted by finite element models

Background: Proximal humeral fractures occur frequently, with fixed angle locking plates often being used for their treatment. No current quantitative evidence for the effect of different screw configurations exists, and the large number of variations makes biomechanical testing prohibitive. Therefore, we used an established and validated finite element osteosynthesis test kit to quantify the effect of variations in screw configuration on predicted failure risk of PHILOS plate fixation for unstable proximal humerus fractures. Methods: Twenty-six low-density humerus models were osteotomized to create malreduced unstable 3-part fractures that were virtually fixed with PHILOS plates. Twelve screw configurations were simulated: 6 using 2 screw rows, 4 using 3 rows, and 1 with either 8 or 9 screws. Three physiological loading cases were modeled and an established finite element analysis methodology was used. The average peri-screw bone strain, previously demonstrated to predict fatigue cutout failure, was used to compare the different configurations. Results: Significant differences in peri-screw strains, and thus predicted failure risk, were seen with different combinations. The 9-screw configuration demonstrated the lowest peri-screw strains. Fewer screw constructs showed lower strains when placed further apart. The calcar screws (row E) significantly (P &lt; .001) reduced fixation failure risk. Conclusion: Screw configurations significantly impact predicted cutout failure risk for locking plate fixations of unstable proximal humerus fractures in low-density bone. Although requiring clinical corroboration, the result of this study suggests that additional screws reduce peri-screw strains, the distance between them should be maximized whenever possible and the calcar screws should be used.</p

The influence of screw length on predicted cut-out failures for proximal humeral fracture fixations predicted by finite element simulations

Background: The aim of this study was to identify the effect of screw length on predictions of fixation failure in three-part proximal humeral fractures using a finite element-based osteosynthesis modelling toolkit. Methods: A mal-reduced unstable three-part AO/OTA 11-B3.2 fracture with medial comminution was simulated in forty-two digitally processed proximal humeri covering a spectrum of bone densities and fixed with the PHILOS plate using three distal and six proximal locking screws. Four test groups were generated based on the screw tip to joint surface distance (TJD), with all proximal screws being shortened from 4 mm TJD to be 8, 12 or 16 mm TJD. Average bone strains around the screw tips, correlating with biomechanical cyclic cut-out-type failure, were evaluated in three physiological loading protocols representing simple shoulder motions. Six further groups were tested, where five of the proximal screws were inserted to 4 mm TJD and the sixth screw to 8 mm TJD. Results: Exponential increases in the predicted risk of fixation failure were seen with increased tip-to-joint distances (p &lt; 0.001). When one of the proximal screws was placed 8 mm from the joint, with the remaining five at 4 mm distance, significant increases (p &lt; 0.001) were registered in the strains around the screw tips in all except the two superior screws. This effect was maximal around the calcar screws (p &lt; 0.001) and for lower density samples (p &lt; 0.001). Conclusions: These results suggest that longer screws provide reduced risk of cut-out failure, i.e. distalisation and/or varisation of the head fragment, and thus may decrease failure rates in proximal humeral fractures treated with angular stable plates. These findings require clinical corroboration and further studies to investigate the risk of screw perforation.</p

Time-dependent density-functional study of the alignment-dependent ionization of acetylene and ethylene by strong laser pulses

The alignment-dependent ionization of acetylene and ethylene in short laser pulses is investigated in the framework of the time-dependent density-functional theory coupled with Ehrenfest dynamics. The molecular alignment is found to have a substantial effect on the total ionization. Bond stretching is shown to cause an increase of the ionization efficiency, i.e., enhanced ionization, in qualitative agreement with previous theoretical investigations. It is also demonstrated that the enhanced ionization mechanism greatly enhances the ionization from the inner valence orbitals, and the ionization of the inner orbitals is primarily due to their extended weakly bound density tail

Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo

Platelet adhesion and aggregation at sites of vascular injury are essential for normal hemostasis but may also lead to pathological thrombus formation, causing diseases such as myocardial infarction or stroke. Heterodimeric receptors of the integrin family play a central role in the adhesion and aggregation of platelets. In resting platelets, integrins exhibit a low affinity state for their ligands, and they shift to a high affinity state at sites of vascular injury. It has been proposed that direct binding of the cytoskeletal protein talin1 to the cytoplasmic domain of the integrin β subunits is necessary and sufficient to trigger the activation of integrins to this high affinity state, but direct in vivo evidence in support of this hypothesis is still lacking. Here, we show that platelets from mice lacking talin1 are unable to activate integrins in response to all known major platelet agonists while other cellular functions are still preserved. As a consequence, mice with talin-deficient platelets display a severe hemostatic defect and are completely resistant to arterial thrombosis. Collectively, these experiments demonstrate that talin is required for inside-out activation of platelet integrins in hemostasis and thrombosis

The Ability of Soil Pore Network Metrics to Predict Redox Dynamics Is Scale Dependent

Variations in microbial community structure and metabolic efficiency are governed in part by oxygen availability, which is a function of water content, diffusion distance, and oxygen demand; for this reason, the volume, connectivity, and geometry of soil pores may exert primary controls on spatial metabolic diversity in soil. Here, we combine quantitative pore network metrics derived from X-ray computed tomography (XCT) with measurements of electromotive potentials to assess how the metabolic status of soil depends on variations of the overall pore network architecture. Contrasting pore network architectures were generated using a Mollisol—A horizon, and compared to intact control samples from the same soil. Mesocosms from each structural treatment were instrumented with Pt-electrodes to record available energy dynamics during a regimen of varying moisture conditions. We found that volume-based XCT-metrics were more frequently correlated with metrics describing changes in available energy than medial-axis XCT-metrics. An abundance of significant correlations between pore network metrics and available energy parameters was not only a function of pore architecture, but also of the dimensions of the sub-sample chosen for XCT analysis. Pore network metrics had the greatest power to statistically explain changes in available energy in the smallest volumes analyzed. Our work underscores the importance of scale in observations of natural systems

Phase 1 dose escalation study of the allosteric AKT inhibitor BAY 1125976 in advanced solid cancer-Lack of association between activating AKT mutation and AKT inhibition-derived efficacy

This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring th

Improved Security Performance for VANET Simulations

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Upcoming deployments of Vehicular Ad Hoc Networks (VANETs) in Europe are expected to sign and verify packets secured by cryptographic signatures by default. Thus, when VANET simulations are used for development and test of applications building upon vehicular communication, the overhead induced by security extensions to the ITS-G5 protocol stack shall not be neglected. This paper presents a standard compliant simulation model capable to handle secured messages. Beside its suitability for Hardware-in-the-Loop simulations employing secured communication, the model's major advantage is the minimisation of the simulation environment's performance penalty linked with cryptographic computations