Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs.

Matrix metalloproteinases (MMPs) are essential proteins acting directly in the breakdown of the extra cellular matrix and so in cancer invasion and metastasis. Given its impact on tumor angiogenesis, monitoring MMP-14 provides strategic insights on cancer severity and treatment. In this work, we report a new approach to improve the electrochemical interaction of the MMP-14 with the electrode surface while preserving high specificity. This is based on the detection of the hemopexin (PEX) domain of MMP-14, which has a greater availability with a stable and low-cost commercial molecule, as a recognition element. This molecule, called NSC-405020, is specific of the PEX domain of MMP-14 within the binding pocket. Through the covalent grafting of the NSC-405020 molecule on carbon nanotubes (CNTs), we were able to detect and quantify MMP-14 using electrochemical impedance spectroscopy with a linear range of detection of 10 ng⋅mL-1 to 100 ng⋅mL-1, and LOD of 7.5 ng⋅mL-1. The specificity of the inhibitory small molecule was validated against the PEX domain of MMP-1. The inhibitor loaded CNTs system showed as a desirable candidate to become an alternative to the conventional recognition bioelements for the detection of MMP-14.

Current level of technology use, health and eHealth literacy in older Canadians with a recent fracture-a survey in orthopedic clinics.

Among older adults who have recently sustained a fracture, there is substantial adoption of mobile technology. Furthermore, health and eHealth literacy level reported by participants supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management. INTRODUCTION: Electronic health resources are increasingly used in the self-management of medical conditions. We aimed to identify the current level of technology adoption, health, and eHealth literacy among older adults with a recent fracture, to determine if the use of electronic interventions would be feasible and acceptable in this population. METHODS: Adults ≥ 50 years with recent fractures were invited to complete a self-administered survey composed of 21 questions, including an 8-item perceived eHealth literacy scale. RESULTS: A total of 401 participants completed the survey (women, 64%; ≥ 65 years, 59%; university education, 32%). Most participants reported no difficulty in reading printed health material (67%) and felt confident in filling out medical forms (65%). Younger age and higher levels of education were associated with higher health literacy. Most respondents (81%) owned at least one mobile device (smartphone, 49%; tablet, 45%). eHEALS scores were similar among men (29, IQR 24-32) and women (29, IQR 25-33), and between younger age group categories (50-64 years, 30; IQR 26-33; and 65-74 years, 29; IQR 25-32), but lower in the oldest age group (≥ 75 years, 24; IQR 21-29; p < 0.05). Compared with the youngest group, those ≥ 75 years had higher odds of an eHEALS < 26 (odds ratio, 4.2; 95% confidence interval 2.0-8.9) after adjusting for sex and education level. CONCLUSION: There is significant adoption of mobile technology among older adults. Health and eHealth literacy reported by this study population supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management.

A recurrent nova super-remnant in the Andromeda galaxy.

The accretion of hydrogen onto a white dwarf star ignites a classical nova eruption1,2-a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of insterstellar medium). Close to the upper mass limit of a white dwarf3 (1.4 solar masses), rapid accretion of hydrogen (about 10-7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years4,5 to decades6. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second7, must 'sweep up' the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known8-10, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually11, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions12, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years.

A pilot study of surgical telementoring for leg fasciotomy.

INTRODUCTION: Acute extremity compartment syndrome requires rapid decompression. In remote locations, distance, weather and logistics may delay the evacuation of patients with extremity trauma beyond the desired timeline for compartment release. The aim of this study was to establish the feasibility of performing telementored surgery for leg compartment release and to identify methodological issues relevant for future research. METHODS: Three anaethetists and one critical care physician were recruited as operators. They were directed to perform a two-incision leg fasciotomy on a Thiel-embalmed cadaver under the guidance of a remotely located orthopaedic surgeon. The operating physician and the surgeon (mentor) were connected through software that allows for real-time supervision and the use of a virtual pointer overlaid onto the surgical field. Two experienced orthopaedic traumatologists independently assessed the adequacy of compartment decompression and the presence of iatrogenic complications. RESULTS: 14 of 16 compartments (in four leg specimens) were felt to have been completely released. The first evaluator considered that the deep posterior compartment was incompletely released in two specimens. The second evaluator considered that the superficial posterior compartment was incompletely released in two specimens. The only complication was a large laceration of the soleus muscle that occurred during a period of blurred video signal attributed to a drop in bandwidth. CONCLUSIONS: This study suggests that surgical telementoring may enable physicians to safely perform two-incision leg fasciotomy in remote environments. This could improve the chances of limb salvage when compartment syndrome occurs far from surgical care. We found interobserver variation in the assessment of compartment release, which should be considered in the design of future research protocols.

Atypical femur fractures: a survey of current practices in orthopedic surgery.

The results of a self-administered online survey demonstrate that orthopedic surgeons' management practices for AFF are variable. These data will inform the development of clinical practice guidelines. INTRODUCTION: We aimed to determine current AFF treatment practices of orthopedic surgeons to inform clinical practice guideline development. METHODS: A self-administered online survey was developed and sequentially posted on the Orthopaedic Trauma Association (OTA) website from July to August 2015 and the Canadian Orthopaedic Association (COA) website from December 2015 to January 2016. Level of confidence in diagnosis and treatment as well as treatment preferences between respondents who self-identified as trauma surgeons vs. non-trauma surgeons were compared. RESULTS: A total of 172 completed surveys were obtained (OTA, N = 100, 58%; COA, N = 72, 8%). Seventy-eight percent of respondents had treated ≥1 AFF in the previous 6 months. Seventy-six percent reported feeling extremely or very confident in diagnosing AFF (trauma 84% vs. non-trauma surgeons 70%, p = 0.04), and 63% reported feeling extremely or very confident in treating AFF (trauma 82%, non-trauma surgeons 50%, p < 0.01). Preferred management for complete and symptomatic incomplete AFFs was surgical fixation with a cephalomedullary nail (CMN) by 88 and 79%, respectively, while close follow-up was preferred for asymptomatic incomplete AFFs in 72% of respondents. Trauma surgeons used the CMN more frequently than non-trauma surgeons (90 vs. 76% p = 0.03). In patients with bilateral AFFs, with one side surgically treated, 56% were extremely likely to surgically treat the contralateral side, if symptomatic. Most felt guidelines (81%) and educational resources (73%) would be valuable. CONCLUSIONS: Current orthopedic treatment practices for AFFs are variable. The results of this survey will inform the development of practice guidelines and educational resources.

Ultrasound-assisted external fixation: a technique for austere environments.

INTRODUCTION: Ultrasound-assisted external fixation of long bones has the potential to enhance extremity damage control surgery in locations without fluoroscopy, such as forward surgical elements, the intensive care unit, and spacecraft. This pre-clinical study specifically sought to evaluate orthopaedic surgeons' ability to sonographically define fracture patterns and the associated zone of injury in order to improve surgical decision-making and safely insert Schanz pin percutaneously. METHODS: We encased small composite femurs in a cylindrical echogenic gelatin matrix to simulate a human thigh. Three orthopaedic trauma surgeons with no prior ultrasound experience were taught to use sonography to diagnose fractures and assist external fixation. The surgeons were then presented with five specimens in a randomized sequence: three diaphyseal fractures (32-A2, 32-C2 and 32-C3); a distal femur fracture (33-A1.2); and an intact femur, all encased in an opaque black gelatin matrix to blind the participants to the underlying pathology. If they diagnosed a diaphyseal fracture, the surgeons were instructed to insert two Schanz pins proximal and two distal to the fracture, no closer than 40 mm from the fracture edges. RESULTS: Fracture diagnosis and surgical decision-making were correct in all cases. All intact femurs were recognized as such. The need for a knee-spanning external fixator was recognized for all distal femur fractures. The three surgeons performed appropriate ultrasound-assisted pin placement in every case of diaphyseal fracture. The pins adjacent to the fracture site were on average 58 mm (SD ±11 mm) from the edge of the fracture. No pins were inserted in the fracture or in the knee joint. CONCLUSIONS: The current study results suggest that with minimal training, orthopaedic surgeons can use portable ultrasound to diagnose femur fractures, decide the appropriate external fixator configuration, and safely insert Schanz pins outside the zone of injury.

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects.

The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid. The cells remained metabolically active in scaffolds incubated in vitro for up to 15 days and differentiated into osteoblasts that deposited calcium-phosphate mineral into the scaffold, which was quantified using micro-computed tomographic (micro-CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded scaffolds were rapidly mineralised and integrated into host bone with administration of 10 ng of recombinant VEGF injected into the femoral canal at 4 days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects that did not receive a bolus dose of VEGF did not mineralise or integrate with native bone. The approach with MSC, hydrogels and a biologic factor already approved for human use warrants further pre-clinical investigation with a large animal model.

FGF18 augments osseointegration of intra-medullary implants in osteopenic FGFR3(-/-) mice.

Enhancement of endogenous bone regeneration is a priority for integration of joint replacement hardware with host bone for stable fixation of the prosthesis. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications for bone regeneration and skeletal repair. This study was designed to determine if treatment with FGF 18 would promote bone regeneration and integration of orthopedic hardware in FGF receptor 3 deficient (FGFR3(-/-)) mice, previously characterized with impaired bone formation. Rigid nylon rods coated with 200 nm of titanium were implanted bilaterally in the femora of adult FGFR3(-/-) and FGFR3(+/+) mice to mimic human orthopedic hardware. At the time of surgery, LEFT femora received an intramedullary injection of 0.5 µg FGF18 (Merck Serono) and RIGHT femora received PBS as a control. Treatment with FGF18 resulted in a significant increase in peri-implant bone formation in both FGFR3(+/+) and FGFR3(-/-) mice, with the peri-implant fibrous tissue frequently seen in FGFR3(-/-) mice being largely replaced by bone. The results of this pre-clinical study support the conjecture that FGF18 could be used in the clinical setting to promote integration of orthopedic hardware in poor quality bone.

Proximal humerus fractures treated by percutaneous locking plate internal fixation.

INTRODUCTION: There is no consensually accepted recommendation for optimum surgical treatment of unstable fractures of the proximal humerus. HYPOTHESIS: Locked and minimally-invasive plating is a promising treatment option. MATERIALS AND METHODS: The aim of this prospective, multicentric study is to describe a recently introduced surgical technique for proximal humeral fractures and to evaluate the radiographic and clinical outcomes of this operation. Closed and minimally-invasive reduction is first performed. A proximal humerus specific locking plate featuring multiple-angle screws is secondly implanted. Proper identification and protection of the axillary nerve with the index finger during plate insertion on the lateral humeral side is highly advisable. If it can't be palpated, a classic delto-pectoral approach should be preferred. Thirty-four patients were included in this study with a 1-year minimal postoperative follow-up. Twenty-two patients presented a two-part surgical neck fracture according to the Neer classification and 12 patients had a three-part valgus-impacted fracture. DASH (Disabilities of the Arm, Shoulder and Hand) and Constant scoring systems were used for functional evaluation. RESULTS: Specifically, no axillary nerve injury and no loss of reduction were observed. The median Constant score and the mean DASH score were 82 and 26 respectively at 1-year follow-up. The age-adjusted functional scores values were satisfactory. Two of the patients (6%) required surgical revision for intra-articular screw penetration. DISCUSSION: Our study suggests that percutaneous plating with angular screw fixation of proximal humeral fractures is a safe and effective method, which produces good functional and radiologic outcomes. These minimally-invasive techniques allowing a better preservation of soft-tissues help promote early functional recovery. This more friendly approach combined to upgraded implants and instruments will also improve early and long-term outcomes of these fractures.

Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia.

OBJECTIVE: The pathophysiology of non-traumatic osteonecrosis (ON) or avascular necrosis (AVN) of the femoral head remains poorly understood. Some studies have suggested the contribution of underlying thrombophilia as a mechanism; however, no specific thrombophilic factor has been consistently found in association with the disease. We are presenting data suggesting a role for endothelial cell activation rather than thrombophilia in ON. METHODS: A prospective consecutive cohort of 49 patients with a diagnosis of ON. The disease was considered idiopathic in five and secondary in 44 patients. The investigation included a coagulation and thrombophilia profile, endothelial cell activation and non-specific inflammatory markers as well as a biochemical profile. Statistical analysis using Fisher's exact test was obtained to assess correlation between endothelial cell markers and variables of inflammation. RESULTS: Patients with non-traumatic ON were not found to have a specific underlying thrombophilic factor compared with the general population. Out of 49 patients,19 had elevation of at least one endothelial cell markers. We found that activation of endothelial cell markers was independently correlated to ON but not correlated to the presence of inflammation (P = 1.0000). CONCLUSION: These results suggest that non-traumatic ON is not associated with a specific thrombophilic abnormality in those affected. This study demonstrates a potential association between regional endothelial dysfunction and ON. More studies are needed at a molecular level to further investigate the specific role of endothelium in the physiopathology of ON. A better understanding of the underlying mechanism could lead to potential preventive and therapeutic strategies of this devastating disease.

A physical vapor deposition method for controlled evaluation of biological response to biomaterial chemistry and topography.

The purpose of this study was to characterize a technique to effectively mask surface chemistry without modifying surface topography. A thin layer of titanium was deposited by physical vapor deposition (PVD) onto different biomaterial surfaces. Commercially pure titanium disks were equally divided into three groups. Disks were either polished to a mirror finish, grit blasted with alumina particles, or grit blasted and subsequently plasma sprayed with a commercial grade of hydroxyapatite (HA). A subgroup of each of these treatment types was further treated by masking the entire disk surface with a thin layer of commercially pure titanium deposited by PVD. A comparison of surface topography and chemical composition was carried out between disks within each treatment group. Canine marrow cells were seeded on all disk surfaces to determine the stability of the PVD Ti mask under culture conditions. The PVD process did not significantly alter the surface topography of any samples. The thin titanium layer completely masked the underlying chemistry of the plasma sprayed HA surface and the chemistry of the plasma vapor deposited titanium layer did not differ from that of the commercially pure titanium disks. Aliquots obtained from the media during culture did not indicate any significant differences in Ti concentration amongst the Ti and Ti-masked surfaces. The PVD application of a Ti layer on HA coatings formed a stable, durable, and homogenous layer that effectively masked the underlying surface chemistry without altering the surface topography.

The effectiveness of orthopaedic trauma theatres in decreasing morbidity and mortality: a study of 701 displaced subcapital hip fractures in two trauma centres.

In countries with universal health care systems patients frequently wait days for their "emergency" surgery. A general trend in orthopaedic traumatology is the advent of daily, dedicated orthopaedic trauma theatres. Availability of trauma theatres is believed to decrease morbidity and mortality, but this remains unproven. A retrospective review comparing morbidity and mortality outcomes between two similar level-one trauma centres (one without a dedicated trauma room system) was undertaken. We reviewed 701 elderly patients receiving hemiarthroplasties for displaced subcapital hip fractures over a 76-month period. Patients were similar between centres in terms of age, gender ratio and comorbidities. Statistically significant differences were found favouring the dedicated trauma room system with approximately half the operative delay and post-operative morbidity. A trend towards decreased mortality was also seen. This study supports the use of regular orthopaedic trauma theatres in tertiary care institutions.

Zoledronic acid causes enhancement of bone growth into porous implants.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

The locked flexible intramedullary humerus nail in pediatric femur and tibia shaft fractures: a feasibility study.

There are several options for the treatment of long bone fractures in skeletally immature patients. Surgeon experience, type of fracture, and the possibility of damage to the physeal area dictate individual fracture management patterns. Notably, nail devices have not gained popularity in this patient group. Intramedullary locking nails have become the standard of care in adult patients due to decreased morbidity and mortality. A novel nail has been developed for humeral shaft fractures that uses a lateral starting position to avoid damage to the rotator cuff in humeral fracture fixation. This is possible because of the nail's transient flexibility during insertion. This study illustrates that it is feasible to insert this type of nail through multiple entry portals for both tibial and femoral fracture fixation, without damaging the physeal blood supply or growth areas.

Minimally invasive dynamic hip screw: prospective randomized trial of two techniques of insertion of a standard dynamic fixation device.

OBJECTIVE: This study evaluates the safety and outcome of a minimally invasive technique for inserting a standard dynamic hip screw for intertrochanteric fractures. HYPOTHESIS: The use of standard plate in a minimally invasive technique is both possible and advantageous to patient outcome. DESIGN AND METHODS: Prospective surgeon-randomized blinded outcome clinical study comparing new technique to conventional technique. MAIN OUTCOME MEASURE: Pain, operative time and mean hemoglobin drop in percutaneous hip fixation. RESULTS: The minimally invasive technique had significantly less blood loss (P < 0.001), operative time (P < 0.001) and a trend to less morphine use. CONCLUSIONS: Minimal invasive technique significantly reduces blood loss and operative time for fixation of intertrochanteric hip fractures without sacrifice of fixation stability or bone healing.

Acid-etched microtexture for enhancement of bone growth into porous-coated implants.

We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of bone ingrowth. Cylindrical titanium intramedullary implants were coated with titanium beads to form a porous finish using commercial sintering techniques. A control group of implants was left in the as-sintered condition. The test group was etched in a boiling acidic solution to create an irregular surface over the entire porous coating. Six experimental dogs underwent simultaneous bilateral femoral intramedullary implantation of a control implant and an acid etched implant. At 12 weeks, the implants were harvested in situ and the femora processed for undecalcified, histological examination. Eight transverse serial sections for each implant were analysed by backscattered electron microscopy and the extent of bone ingrowth was quantified by computer-aided image analysis. The extent of bone ingrowth into the control implants was 15.8% while the extent of bone ingrowth into the etched implants was 25.3%, a difference of 60% that was statistically significant. These results are consistent with other research that documents the positive effect of microtextured surfaces on bone formation at an implant surface. The acid etching process developed for this study represents a simple method for enhancing the potential of commonly available porous coatings for biological fixation.

The use of a locking custom contoured blade plate for peri-articular nonunions.

A retrospective chart and radiographic review was performed of 37 operative procedures over 7 years period for peri-articular nonunions. This was a consecutive cohort from a single orthopedic trauma service of a Level 1 center. Nonunions of the tibia and humerus were treated with blade plates fashioned from standard compression plates. Twenty-nine operative sites were treated successfully. The average age was 45.0 years; the average follow-up being 5.3 years. The average number of operations before blade plate was 4.0 (range 1-16). Sixteen blade plates were performed in patients with a diagnosis of clinical infection and all progressed to union and resolution of infection. Seven tissue transfers were used as adjunctive therapy. Five other patients with blade plate surgery had persistent nonunion, of which four united after a second custom contoured blade plate procedure. This study illustrates that surgeon contoured blade plates are an option for peri-articular nonunions even in the presence of infection. This technique resulted in a high union rate and a low complication rate compared to other options.

Relative contributions of chemistry and topography to the osseointegration of hydroxyapatite coatings.

The purpose of the current study was to ascertain the relative contributions of surface chemistry and topography to the osseointegration of hydroxyapatite-coated implants. A canine femoral intramedullary implant model was used to compare the osseous response to commercially pure titanium implants that were either polished, grit-blasted, plasma-sprayed with hydroxyapatite, or plasma-sprayed with hydroxyapatite and masked with a very thin layer of titanium using physical vapor deposition (titanium mask). The titanium mask isolated the chemistry of the underlying hydroxyapatite layer without functionally changing its surface topography and morphologic features. At 12 weeks, the bone-implant specimens were prepared for undecalcified thin section histologic evaluation and serial transverse sections were quantified with backscattered scanning electron microscopy for the percentage of bone apposition to the implant surface. Bone apposition averaged 3% for the polished implants and 23% for the grit-blasted implants. Bone apposition to the hydroxyapatite-coated implants averaged 74% whereas bone apposition to the titanium mask implants averaged 59%. Although there was significantly greater osseointegration with the hydroxyapatite-coated implants, 80% of the maximum bone forming response to the implant surfaces developed with the titanium mask implants. This simple, controlled experiment revealed that topography is the dominant factor governing bone apposition to hydroxyapatite-coated implants.

Deleterious effect of smoking on healing of open tibia-shaft fractures.

We retrospectively reviewed a prospectively followed cohort of 105 patients with 110 open tibia fractures treated with external fixator or intramedullary nail to determine whether smoking affects fracture healing. Severe open tibia-shaft fractures treated at a tertiary-care medical center were included. Patients with type II, IIIA, or IIIB tibia fractures were eligible. Treatment for all patients was similar, except that they were randomized to receive external fixator or intramedullary nail. Time to fracture healing was the main outcome measurement. Smokers had a union rate of 84% (52/62), and nonsmokers had a union rate of 94% (45/48), P = .10. For smokers in one arm of the study, time to union was significantly longer (P = .01), and there were more complications (P = .04). Smoking decreased unions, slowed healing, and increased complications.