Arthroscopic Glenoid Bone Augmentation Using Iliac Crest Autograft Is Safe and Effective for Anterior Shoulder Instability With Bone Loss.

PURPOSE: To establish a safety profile for an arthroscopic anatomic glenoid reconstruction using autologous iliac crest bone graft to treat shoulder instability with significant bone loss and to evaluate short-term clinical and radiological outcomes. METHODS: A retrospective analysis of prospectively collected data was conducted for the patients who were treated for shoulder instability with bone loss using arthroscopic autologous iliac crest bone graft between November 2014 and June 2018. The safety profile was established by detective intraoperative or postoperative complications such as neurovascular injuries, infections, major bleeding, and subluxations. Short-term clinical and radiologic outcomes also were evaluated. RESULTS: Thirteen patients were included in the study. A safety profile was observed, with no occurrence of intraoperative complications, neurovascular injuries, infection, or major bleeding. There were no dislocations or positive apprehension tests on clinical examination postoperatively. Postoperative Western Ontario Shoulder Instability (WOSI) scores were significantly greater than preoperative WOSI scores, with a mean improvement of 35.0 ± 20.2 (P < .001). Twelve patients (92.3%) received postoperative computed tomography scans, with 11 of 12 patients (91.7%) displaying complete graft union. CONCLUSIONS: Arthroscopic treatment of shoulder instability with bone loss via autologous iliac crest bone graft is shown to be a safe operative procedure that results in favourable short-term clinical and radiologic outcomes, with a significant improvement in WOSI scores and high rates of graft union. Although graft resorption was seen in most patients who had postoperative computed tomography imaging, there were no instances of clinical graft failure. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

An adaptive finite element model for steerable needles.

Penetration of a flexible and steerable needle into a soft target material is a complex problem to be modelled, involving several mechanical challenges. In the present paper, an adaptive finite element algorithm is developed to simulate the penetration of a steerable needle in brain-like gelatine material, where the penetration path is not predetermined. The geometry of the needle tip induces asymmetric tractions along the tool-substrate frictional interfaces, generating a bending action on the needle in addition to combined normal and shear loading in the region where fracture takes place during penetration. The fracture process is described by a cohesive zone model, and the direction of crack propagation is determined by the distribution of strain energy density in the tissue surrounding the tip. Simulation results of deep needle penetration for a programmable bevel-tip needle design, where steering can be controlled by changing the offset between interlocked needle segments, are mainly discussed in terms of penetration force versus displacement along with a detailed description of the needle tip trajectories. It is shown that such results are strongly dependent on the relative stiffness of needle and tissue and on the tip offset. The simulated relationship between programmable bevel offset and needle curvature is found to be approximately linear, confirming empirical results derived experimentally in a previous work. The proposed model enables a detailed analysis of the tool-tissue interactions during needle penetration, providing a reliable means to optimise the design of surgical catheters and aid pre-operative planning.

Minimally disruptive needle insertion: a biologically inspired solution.

The mobility of soft tissue can cause inaccurate needle insertions. Particularly in steering applications that employ thin and flexible needles, large deviations can occur between pre-operative images of the patient, from which a procedure is planned, and the intra-operative scene, where a procedure is executed. Although many approaches for reducing tissue motion focus on external constraining or manipulation, little attention has been paid to the way the needle is inserted and actuated within soft tissue. Using our biologically inspired steerable needle, we present a method of reducing the disruptiveness of insertions by mimicking the burrowing mechanism of ovipositing wasps. Internal displacements and strains in three dimensions within a soft tissue phantom are measured at the needle interface, using a scanning laser-based image correlation technique. Compared to a conventional insertion method with an equally sized needle, overall displacements and strains in the needle vicinity are reduced by 30% and 41%, respectively. The results show that, for a given net speed, needle insertion can be made significantly less disruptive with respect to its surroundings by employing our biologically inspired solution. This will have significant impact on both the safety and targeting accuracy of percutaneous interventions along both straight and curved trajectories.

Soft Tissue Phantoms for Realistic Needle Insertion: A Comparative Study.

Phantoms are common substitutes for soft tissues in biomechanical research and are usually tuned to match tissue properties using standard testing protocols at small strains. However, the response due to complex tool-tissue interactions can differ depending on the phantom and no comprehensive comparative study has been published to date, which could aid researchers to select suitable materials. In this work, gelatin, a common phantom in literature, and a composite hydrogel developed at Imperial College, were matched for mechanical stiffness to porcine brain, and the interactions during needle insertions within them were analyzed. Specifically, we examined insertion forces for brain and the phantoms; we also measured displacements and strains within the phantoms via a laser-based image correlation technique in combination with fluorescent beads. It is shown that the insertion forces for gelatin and brain agree closely, but that the composite hydrogel better mimics the viscous nature of soft tissue. Both materials match different characteristics of brain, but neither of them is a perfect substitute. Thus, when selecting a phantom material, both the soft tissue properties and the complex tool-tissue interactions arising during tissue manipulation should be taken into consideration. These conclusions are presented in tabular form to aid future selection.

Method to Reduce Target Motion Through Needle-Tissue Interactions.

During minimally invasive surgical procedures, it is often important to deliver needles to particular tissue volumes. Needles, when interacting with a substrate, cause deformation and target motion. To reduce reliance on compensatory intra-operative imaging, a needle design and novel delivery mechanism is proposed. Three-dimensional finite element simulations of a multi-segment needle inserted into a pre-existing crack are presented. The motion profiles of the needle segments are varied to identify methods that reduce target motion. Experiments are then performed by inserting a needle into a gelatine tissue phantom and measuring the internal target motion using digital image correlation. Simulations indicate that target motion is reduced when needle segments are stroked cyclically and utilise a small amount of retraction instead of being held stationary. Results are confirmed experimentally by statistically significant target motion reductions of more than 8% during cyclic strokes and 29% when also incorporating retraction, with the same net insertion speed. By using a multi-segment needle and taking advantage of frictional interactions on the needle surface, it is demonstrated that target motion ahead of an advancing needle can be substantially reduced.

Needle geometry, target migration and substrate interactions in high resolution.

Recent investigations considering flexible, steer-able needles for minimally invasive surgery have shown the significance of needle shape in determining the needle-tissue interactions leading to the access of targets. Digital Image Correlation has enabled internal deformation and strain caused by needle insertions to be seen in a soft tissue phantom at high resolution for the first time. Here, the impact of tip design on strains and displacements of material around the insertion axis is presented using Digital Image Correlation in a stable, plane-strain configuration. Insight into the shape of needles to minimise tissue trauma and generate interactions that would enable optimal steering conditions is provided. Needle tips with an included bevel angle up to 40° result in asymmetric displacement of the surrounding tissue phantom. Increasing the included tip angle to 60° results in more predictable displacement and strains that may enhance steering forces with little negative impact on the phantom.

Detailed finite element modelling of deep needle insertions into a soft tissue phantom using a cohesive approach.

Detailed finite element modelling of needle insertions into soft tissue phantoms encounters difficulties of large deformations, high friction, contact loading and material failure. This paper demonstrates the use of cohesive elements in high-resolution finite element models to overcome some of the issues associated with these factors. Experiments are presented enabling extraction of the strain energy release rate during crack formation. Using data from these experiments, cohesive elements are calibrated and then implemented in models for validation of the needle insertion process. Successful modelling enables direct comparison of finite element and experimental force-displacement plots and energy distributions. Regions of crack creation, relaxation, cutting and full penetration are identified. By closing the loop between experiments and detailed finite element modelling, a methodology is established which will enable design modifications of a soft tissue probe that steers through complex mechanical interactions with the surrounding material.

Tissue deformation analysis using a laser based digital image correlation technique.

A laser based technique for planar time-resolved measurements of tissue deformation in transparent biomedical materials with high spatial resolution is developed. The approach is based on monitoring the displacement of micrometer particles previously embedded into a semi-transparent sample as it is deformed by some form of external loading. The particles are illuminated in a plane inside the tissue material by a thin laser light sheet, and the pattern is continuously recorded by a digital camera. Image analysis yields the locally and temporally resolved sample deformation in the measurement plane without the need for any in situ measurement hardware. The applicability of the method for determination of tissue deformation and material strain during the insertion of a needle probe into a soft material sample is demonstrated by means of an in vitro trial on gelatin.

Predicting failure in soft tissue phantoms via modeling of non-predetermined tear progression.

The advantageous, curved trajectory of bevel-tipped devices in soft tissue is a function of the interplay between material deformation, contact interactions and material failure. Highly detailed modeling of tool-tissue interactions is therefore vital in optimising performance and design. At high resolution, discontinuous failure of soft tissue phantoms has not been demonstrated. An iterative procedure, making incremental additions to the failure path in an otherwise continuous finite element mesh, is presented to achieve this goal. The procedure's efficacy was demonstrated in two materials including a soft tissue phantom. Failure path is shown to respond well to different and evolving shear and normal stress states. The iterative procedure would thus be ideal for analysing and optimising complex tool-tissue interactions, for instance in needle steering systems, where the path taken by the needle also depends on the progression of a tear which develops ahead of the tip during the insertion process. With the method presented here, this behaviour could be modeled and analysed at an unprecedented resolution.

Detailed finite element simulations of probe insertion into solid elastic material using a cohesive zone approach.

In this paper a method is presented for detailed finite element modelling of probe insertion into an elastic material. This is part of an ongoing investigation into the mechanics of a novel, biomimetic, soft-tissue probe currently under development at Imperial College, London. Analysis is performed using a 'cohesive zone' approach by integrating multiple cohesive elements into a finite element mesh using Abaqus software. Cohesive zones with variable crack paths, generated by both remote tensile and contact loading, and substantial probe penetration along an arbitrarily curved crack path are demonstrated. These advances are critical to understanding probe interactions for the development of an existing prototype and control strategy.

Long term prognosis of women with gestational diabetes in a multiethnic population.

AIM: To assess the glucose tolerance of South Asian and Caucasian women with previous gestational diabetes mellitus (GDM). METHOD: A retrospective follow-up study of 189 women diagnosed with GDM between 1995 and 2001. Glucose tolerance was reassessed by oral glucose tolerance test at a mean duration since pregnancy of 4.38 years. RESULTS: South Asian women comprised 65% of the GDM population. Diabetes developed in 36.9% of the population, affecting more South Asian (48.6%) than Caucasian women (25.0%). Women developing diabetes were older at follow-up (mean (SD) 38.8 (5.7) vs 35.9 (5.6) years; p<0.05) and had been heavier (body mass index 31.4 (6.3) vs 27.7 (6.7) kg/m(2); p<0.05), more hyperglycaemic (Gl(0) 6.5 (1.7) vs 5.2 (1.1) mmol/l; p<0.01: G(120) 11.4 (3.3) vs 9.6 (1.8) mmol/l; p<0.01: HbA1c 6.4 (1.0) vs 5.6 (0.7); p<0.01) and more likely to require insulin during pregnancy (88.1% vs 34.0%; p<0.01). Future diabetes was associated with and predicted by HbA1c taken at GDM diagnosis in both South Asian (odds ratio 4.09, 95% confidence interval 1.35 to 12.40; p<0.05) and Caucasian women (OR 9.15, 95% CI 1.91 to 43.87; p<0.01) as well as by previously reported risk factors of increasing age at follow-up, pregnancy weight, increasing hyperglycaemia and insulin requirement during pregnancy. CONCLUSION: GDM represents a significant risk factor for future DM development regardless of ethnicity. Glycated haemoglobin values at GDM diagnosis have value in predicting future diabetes mellitus.

Advanced glycation end products induce tubular epithelial-myofibroblast transition through the RAGE-ERK1/2 MAP kinase signaling pathway.

Advanced glycation end products (AGEs) have been shown to play a role in tubular epithelial-myofibroblast transdifferentiation (TEMT) in diabetic nephropathy, but the intracellular signaling pathway remains unknown. We report here that AGEs signal through the receptor for AGEs (RAGE) to induce TEMT, as determined by de novo expression of a mesenchymal marker (alpha-smooth muscle actin, alpha-SMA) and loss of epithelial marker (E-cadherin), directly through the MEK1-ERK1/2 MAP kinase pathway, which is TGF-beta independent. This is supported by the following findings: AGEs induced de novo alpha-SMA mRNA expression as early as 2 hours followed by a loss of E-cadherin before TGF-beta mRNA expression at 24 hours and occurred in the absence of TGF-beta and AGE-induced activation of ERK1/2 MAP kinase at 15 minutes and TEMT at 24 hours were completely blocked by a neutralizing RAGE antibody, a soluble RAGE receptor, an ERK1/2 MAP kinase inhibitor (PD98059), and DN-MEK1, but not by a neutralizing TGF-beta antibody. Thus, this study demonstrates that AGEs activate the RAGE-ERK1/2 MAP kinase pathway to mediate the early TEMT process. The findings from this study suggest that targeting the RAGE or the ERK MAP kinase pathway may provide new therapeutic strategies for diabetic nephropathy and shed new light on the pathogenesis of diabetic nephropathy.

Advanced glycation end products activate Smad signaling via TGF-beta-dependent and independent mechanisms: implications for diabetic renal and vascular disease.

While it is thought that advanced glycation end products (AGEs) act by stimulating transforming growth factor (TGF)-beta to mediate diabetic injury, we report that AGEs can activate TGF-beta signaling, Smads, and mediate diabetic scarring directly and independently of TGF-beta. AGEs activate Smad2/3 in renal and vascular cells at 5 min, peaking over 15-30 min before TGF-beta synthesis at 24 h and occurs in TGF-beta receptor I and II mutant cells. This is mediated by RAGE and ERK/p38 mitogen-activated protein kinases (MAPKs). In addition, AGEs also activate Smads at 24 h via the classic TGF-beta-dependent pathway. A substantial inhibition of AGE-induced Smad activation and collagen synthesis by ERK/p38 MAPK inhibitors, but not by TGF-beta blockade, suggests that the MAPK-Smad signaling crosstalk pathway is a key mechanism in diabetic scarring. Prevention of AGE-induced Smad activation and collagen synthesis by overexpression of Smad7 indicates that Smad signaling may play a critical role in diabetic complications. This is further supported by the findings that activation of Smad2/3 in human diabetic nephropathy and vasculopathy is associated with local deposition of AGEs and up-regulation of RAGE. Thus, AGEs act by activating Smad signaling to mediate diabetic complications via both TGF-beta-dependent and -independent pathways, shedding new light on the pathogenesis of diabetic organ injury.

Role of advanced glycation end products in diabetic nephropathy.

Nonenzymatic reactions between sugars and the free amino groups on proteins, lipids, and nucleic acids result in molecular dysfunction through the formation of advanced glycation end products (AGE). AGE have a wide range of chemical, cellular, and tissue effects through changes in charge, solubility, and conformation that characterize molecular senescence. AGE also interact with specific receptors and binding proteins to influence the expression of growth factors and cytokines, including TGF-beta1 and CTGF, thereby regulating the growth and proliferation of the various renal cell types. It seems that many of the pathogenic changes that occur in diabetic nephropathy may be induced by AGE. Drugs that either inhibit the formation of AGE or break AGE-induced cross-links have been shown to be renoprotective in experimental models of diabetic nephropathy. AGE are able to stimulate directly the production of extracellular matrix and inhibit its degradation. AGE modification of matrix proteins is also able to disrupt matrix-matrix and matrix-cell interactions, contributing to their profibrotic action. In addition, AGE significantly interact with the renin-angiotensin system. Recent studies have suggested that angiotensin-converting enzyme inhibitors are able to reduce the accumulation of AGE in diabetes, possibly via the inhibition of oxidative stress. This interaction may be a particularly important pathway for the development of AGE-induced damage, as it also can be attenuated by antioxidant therapy. In addition to being a consequence of oxidative stress, it is now clear that AGE can promote the generation of reactive oxygen species. It is likely that therapies that inhibit the formation of AGE will form an important part of future therapy in patients with diabetes, acting synergistically with conventional approaches to prevent diabetic renal injury.