bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Stretching of Fibrillar Collagen Enhances Cross-linking by Transglutaminas
Authors: Shealy Nicolas , Rex James , Bradshaw Amy , Gross Christopher 
Published: October 2019

Category: Basic Sciences/Biologics Introduction/Purpose: New approaches to improve tendon repair after injury are an active area of research. Critical properties of tendons are governed by the production and assembly of fibrillar collagens. Cross-linking of fibrillar collagen is a primary factor in determining the function and mechanical properties of the collagen fibers comprising Enzymatic cross-linking by lysyl oxidase in the telopeptide domain of collagen I and III is one determinant of collagen fibril assembly and is the best characterized biochemical cross-link. Transglutaminase catalyzes the modification of lysine residues that in turn form an n-e-glutamyl lysine bond between proteins in the extracellular space. We hypothesize that transglutaminase-dependent modification of collagen in tendons is also a principal determinant of tendon strength and function and is dependent upon tension. Methods: 3-D collagen gels were generated from acid solubilized type I collagen with telopeptides (Advanced BioMatrix). Collagen gels were plated and loaded into a MechanoCulture FX apparatus (CellScale). Gels were subjected to a 10% stretch for 24 hrs at 37°C at 2hz (dynamic) or no stretch, static controls. Gels exposed to enzymatic cross-linking were incubated with either 2.4 ng of recombinant Transglutaminase 2 (Axxora) in a 10 mM Ca2+ solution. Inhibition and labeling of transglutaminase substrates was performed by incubation of collagen gels with 0.2 mM aminopentyl biotinamide in DMSO. Soluble collagen was separated from insoluble collagen by centrifugation at 10,000G. Insoluble fractions were boiled in SDS-Laemmli buffer prior to separation by SDS-PAGE. Collagen in soluble and insoluble fractions was evaluated by Coomassie stain whereas transglutaminase modification was detected via western blot using streptavidin conjugated horse radish peroxidase to detect biotinylated proteins. Results: Evaluation of collagen gels subjected to dynamic versus static stretch revealed minor differences in insoluble collagen incorporation in the two conditions. Notably, higher molecular weight cross-linked forms of collagen appeared to be higher in dynamic versus static gels. In the presence of transglutaminase, differences in higher molecular weight cross-linked forms of collagen, beta-bands, were also detected. Finally, incorporation of biotinylated transglutaminase substrate into collagen alpha bands was enriched in dynamic versus static cultures. Hence, preliminary results support a differential role for transglutaminase modification in collagen under cyclic tension versus static conditions. Conclusion: A better understanding of the role of dynamic stretching and differential tension in the regulation of collagen cross- link formation is predicted to contribute to improved strategies to treat injured tendons.
Retrospective Radiographic Evaluation of AugmentTM Bone Graft Fusion
Authors: Shelton Trevor J. , Sheih Alvin K. , Chang Eric , Steele Amy E. , Giza Eric , Kreulen Christopher D. 
Published: October 2019

Category: Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot Introduction/Purpose: Augment is the first Food and Drug Administration approved synthetic bone substitute specifically formulated for foot and ankle procedures and have shown results comparable to autograft. Initial studies on the use of Augment for fusion procedures of the foot and ankle are encouraging but there remains a lack of radiographic outcomes on its use. The purposes of this study were to report on the radiographic fusion rate of Augment and identify risk factors for nonunion in patients treated with Augment. Methods: After institutional review board approval, a retrospective study was performed of all patients ages 18-85 who underwent arthrodesis of the ankle, hindfoot, or midfoot and used Augment alone or in combination with autograft and/or allograft. Patients were excluded if they did not have regular radiographic follow-up. Each operative report was examined for procedure performed and location of the foot involved. Post-operative radiographs were reviewed to look at union rate following surgery. Patient charts were reviewed for age, gender, Body Mass Index (BMI), smoking history, and diabetes to examine potential risk factors for nonunion. Continuous variables were reported in means ± standard deviations and differences determined between those that fused and those that did not using a Wilcoxon Rank Sums test. Categorical variables reported as number of patients (percent of patients) and differences determined between those that fused and those that did not using a Fisher’s exact test. Results: A total of 71 patients (average age at injury 57±14 years; 35 males (49%), 36 females (50%); BMI 31±6) underwent 33 (46%) midfoot arthrodesis, 41 (58%) hindfoot arthrodesis, and 27 (38%) ankle arthrodesis. A total of 58 patients (82%) went on to achieve fusion while 13 (18%) did not. There was no difference in gender (p=0.135), age (p=0.345) or BMI (p=0.196) between those who achieved fusion and those who did not. Patients with diabetes had a greater risk of nonunion compared to those who did not (p=0.033) while current smoking status or revision fusion did not pose a risk factor (p=1.000) (Table 1). There were no differences in part of the foot/ankle involved (p=0.445) or bone graft used (p=0.303). Conclusion: This the first study to examine the radiographic follow up of union using Augment. The most important finding of this study is that the rate of fusion in foot and ankle arthrodesis using Augment is near 82%. Diabetes is a risk factor for nonunion when using Augment. Smoking, gender, age, BMI, autograft vs allograft, and part of the foot or ankle fused did not pose a risk factor.
Ankle Distraction Arthroplasty combined with PRP injection for Post-traumatic Ankle Arthritis
Authors: Shi Zhongmin , Gu Wenqi 
Published: October 2019

Category: Ankle Arthritis Introduction/Purpose: To summarize and evaluate the surgical technique and clinical outcome of ankle distraction arthroplasty with PRP injection for post-traumatic ankle arthritis. Methods: Totally 21 patients of post-traumatic ankle arthritis were treated at the department of orthopaedic surgery, Shanghai Sixth People’s Hospital. They were 13 males and 8 females with an average age of 32.5±6.2 years. The average course of disease were 14.0±2.8 months. After the failure of conservative management for at least 6 months, ankle distraction arthroplasty with PRP injection was performed in all patients. American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hindfoot score system and Visual Analogue Scale (VAS) system were used to evaluate the final overall outcome. The range of motion (ROM) of ankle joint and complications were also recorded. Results: Pin tract infection was occurred in two patients, who were cured by alcohol care. 18 patients were followed for an average 36 months. The post-operative AOFAS ankle and hindfoot score was improved from 46.2±7.7 to 79.2±11.6 (t=-14.58, P ＜0.05), while the VAS score was decreased from 6.6±1.1 to 1.8±2.0 (t=16.424, P＜0.0001). The dorsal extension of ankle joint was increased from 1.3±9.3° to 8.1±5.5° (t=-4.675, P＜0.0001) and the plantar flexion was improved from 14.4±6.8° to 26.9±7.3°(t=-7.919, P＜0.05). The radiograph manifested the progressive course of ankle arthritis in four patients, two of which were cured by a salvage ankle arthrodesis by consequence of a failure of conservative treatment for persistent pain and functional limitation. Conclusion: The ankle distraction arthroplasty is an effective ankle preserving surgery, which could relieve symptoms, improve functions and delay the course of post-traumatic ankle arthritis
Return to Play and Rehabilitation Protocols following Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus: A Systematic Review and Meta-Analysis
Authors: Shimozono Yoshiharu , Seow Dexter , Gianakos Arianna L , Chiarello Eugenio , Kennedy John G. 
Published: October 2019

Category: Ankle, Sports Introduction/Purpose: Autologous osteochondral transplantation (AOT) has demonstrated favourable outcomes in the treatment of osteochondral lesions of the talus (OLT). Recent studies have reported high rates of return to play sports following AOT for OLT, however variable rates of return to play have been reported ranging from 50 to 95%. In addition, little information regarding optimal standardized rehabilitation protocols and return to play guidelines has been demonstrated. The purpose of this study is to determine the rate of return to play following AOT for OLT by systematic review and meta-analysis and report subsequent rehabilitation protocols. Methods: The MEDLINE, EMBASE and The Cochrane Library databases was evaluated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using specific inclusion/exclusion criteria. The quality of evidence was evaluated using the Modified Coleman Methodology Score (MCMS). Predetermined data was extracted on a datasheet with the return to play calculated as a percentage of patients that returned to sport. Rehabilitation protocols were recorded as the earliest time that range of motion, partial weightbearing and full weightbearing commenced was recorded. The quality of return to play guidelines in each study was evaluated based on the criteria by Zaman et al. Well defined return to play criteria was allocated a score of 4, poorly defined criteria allocated a score between 1 to 3 and no return to play criteria allocated 0. The meta-analysis of return to play was performed using previously published criteria. Results: The search strategy yielded 8 studies evaluating 200 ankles with a mean follow-up of 44.3 ± 26.8 months (range, 16 to 84 months), mean age of 31.3 ± 6.92 years (range, 22.7 to 42 years) and mean OLT size of 119.2 ± 35.3 mm2 (range, 68.9 to 180 mm2). The mean time to return to play was 4.55 ± 2.19 months (range, 3 to 6.1 months). The reported rates of return to play ranged from 50% to 95.2%. The accumulative rate of return to play was 83.8% (140/167), with 77.4% (48/62) of athletes returning to pre-injury status. Based on the fixed-effect model, the rate of return to play was 81.5% (Figure 1). The quality of return to play criteria was poor in all. Conclusion: This systematic review indicates high rate of return to play following AOT in the athletic population. Rehabilitation protocols were largely inconsistent and were primarily based on individual surgeon protocols. The included studies were of low level and quality of evidence, therefore, further well-designed studies are warranted to sufficiently improve the reporting accuracy for rate of return to play.
Normalization of Microbiome after Diabetic Foot Ulcer Treatment
Authors: Stephens Sebastien , Stephens Alexandre , Platt Simon 
Published: October 2019

Category: Diabetes Introduction/Purpose: Diabetic ulcers carry with it extensive morbidity. The microbiome of diabetic foot infections have previously been shown to be polymicrobial. We hypothesized that ulcer treatment would normalize the foot microbiome. Methods: Microbiome profiles of the fore, mid and hind diabetic foot. Diabetic foot (with ulcer) were taken pre and post treatment with a combination of surgical debridement, local and systemic antibiotics. 10 subjects were studied. Microbiome graphs and images pre and post treatment of feet are shown. Results: The microbiome profile of the diabetic foot almost completely normalized to that of normal flora. Before treatment, the foot microbiome was associated with polymicrobial pathogenic bacteria mostly away from the ulcer. The ulcer itself only contained minimal species, albeit pathogenic bacteria. The differences in profiles between the pre and post treatment were significantly different p < 0.01. Conclusion: Chicken or egg, the foot microbiome almost completely reverts to normal flora with simple ulcer debridement and local/systemic antibiotics. Our data point possibly suggest ulcers could be prevented by reducing pathogenic microbiome load (chlorhexidine washes) or microbiome transplants. We next move to controls as a proof of concept.
Charcot Foot and the Osteoclast: More Than Just Cytokines
Authors: Stephens Sébastien , Platt Simon 
Published: October 2019

Category: Basic Sciences/Biologics Introduction/Purpose: Charcot foot is a serious complication of diabetes present in up to 13% carrying with high morbidity (dislocations, fractures, deformities) and up to 14% mortality. In Charcot, osteoclasts are found in increased numbers and with increased activity3,4 while C-telopeptide of type I collagen (CTX) is upregulated as opposed to ALP suggesting this is indeed an osteoclast and not an osteoblast disease. Methods: The scientific literature was reviewed to identify relevant osteoclastic activators and their role in the hyper activated state. We will also show videos of our current micromanipulation research techniques used to study osteoclast inhibitors in the lab. Results: The blood of Charcot patients is different at the nano level. Micro-nano-particles are extracellular vesicles derived from cells into plasma. Microparticles are found in increased quantity in Charcot;which contain more cytokines; known osteoclast activators. MicroRNAs – Epigenetic changes also are in Charcot; 16 different circulating microRNA known osteoclast activators are associated with Charcot. Advanced glycation end products (AGE). The hyperglycemic state in Charcot is a driving force in pathogenesis. AGEs are normal proteins turned dud after hyperglycemic induced glycation, a post translational modification which is irreversible affects both intracellular and extracellular proteins. AGEs may bind receptor RAGE, increasing osteoclast activity . RANKL is the main osteoclast differentiator and activator. RANKL has been the target of osteoclast control almost since it was found in 1998 . Conclusion: Charcot mediated bony destruction and remodeling; both of which are mediated by the osteoclast has traditionally had a tremendous cytokine focus. Our review suggests the mechanism for modifying a Charcot response on a local and systemic level. It is interesting to note that osteoclast inhibitors Denosumab, Bisphosphonates, Calcitonin and osteoblcast activators rPTH are not completely effective in switching off the Charcot response, implying there is a far more complex interaction between the inflammatory response, osteoclastic stimulators and osteoblastic inhibitors.
Kinematics of a Pyrocarbon Ankle Spacer for the Treatment of Arthritic Disease
Authors: Sturnick Daniel R. , Saltzman Charles L. , Burstein Albert H. , Hamilton Matthew A. , Deland Jonathan T. 
Published: October 2019

Category: Ankle, Ankle Arthritis Introduction/Purpose: Treatment options for ankle arthritis in younger patients are currently limited. Since the longevity of modern total ankle replacements is not sufficient for this patient population, ankle arthrodesis is typically utilized when joint preserving treatment is not a viable option. A new procedure using a pyrocarbon ankle spacer has been developed as a potential alternative, allowing for talar articular resurfacing for pain relief with minimal bone resection. The objective of this study was to assess whether this pyrocarbon ankle spacer could provide normal ankle kinematics as the native ankle joint using cadaveric gait simulation. Methods: Five mid-tibia cadaveric specimens without deformity and no history of lower limb injury or surgery were utilized. The stance phase of gait was simulated for each specimen using a six degree-of-freedom robotic device. A force plate was moved relative to stationary specimen through an inverse tibial kinematic path calculated from in vivo data while extrinsic tendons were actuated using physiologic loads (Figure 1A). Magnitudes of load were scaled to that of 25% bodyweight. Ankle kinematics were measured from reflective markers attached to the tibia and talus via surgical pins. The pyrocarbon ankle spacer (Exactech, Gainesville, FL, USA) was implanted in a nest formed 3-4 mm in depth on the talar articular surface using a custom burring technique (Figure 1B). Ankle spacer kinematics were compared to 95% confidence intervals of native, intact ankle joint kinematics to assess agreement. Results: Outcomes revealed no significant difference in ankle joint kinematics between the native, intact condition and post- pyrocarbon spacer implantation (Figure 1C). This result was consistent for the sagittal, coronal and axial planes of motion. Conclusion: The results of this study demonstrate that a pyrocarbon spacer permits normal ankle kinematics. Further, the device was observed to be stable in the joint throughout simulations. While the testing was performed at 25% bodyweight for analyses on all specimens, load magnitudes were also increased up to 75% on a subset of specimens and the structural integrity of the device remained pristine. With these findings, we concluded that the pyrocarbon spacer device offers promising potential as a treatment option for ankle arthritis.
Interphanlangeal and First Metatarsophalangeal Joint Fusion for Osteomyelitis and Septic Arthritis in Patients with Forefoot Diabetic Foot Ulcers
Authors: Ulrich Martin K. , Iselin Lukas D 
Published: October 2019

Category: Diabetes, infection Introduction/Purpose: In cases of Diabetic Foot ulcers over joints with assocuated septic arthritis or osteomylitis, the erradication of the infection can be difficult to achieve. In order to avoid amputations which are often associated with reduced quality of life, we try to be as conservative as possible in order to save as many big toes as possible. The backbone of our noval treatment protocol involve performing a thorough soft tissue and bony debridement, stabilizing the infected bones or joint by fusing them in the acute phase, and closing the skin over the infected ulcer. We present our experience of this concept. Methods: Retrospective study between the years 2012-2016, in a single centre, treating diabetic foot patients. 29 patients, 31 feet, were identified with IPj or 1st MTPJ fusion for Infection. All patients had a combination of bone and soft tissue infections. All patients had a preoperative radiograph, 22patients had a pre-operative MRI scan to define the extent of the bony and soft-tissue infection. In all cases the involved joint was fused in the acute phase using screws, kw’s, plates, combination of the above fusion techniques. In all cases the skin was closed above the infected ulcer. Results: Closed ulcers of the fitst ray after fusing the infected joint were achieved in 26 patients (84%) by 12 months after surgery. The radiographic fusion rate was 55% by one year after surgery while 77% of the cases were clinically stable by 1 year after surgery. 5 patients (16%) endend up with an amputation. In 4 of them the base of the proximal phalangx could be left to ensure the biomechanical properties as good as possible. 1 patient needed a BKA. In 26 patients, pathogens could be identified; in 77%, polymicrobial flora were found. Conclusion: Arthrodesis of IPJ- or 1st MTPJ in diabetic foot patients presents a successful way of treatmentin order to achieve a stable situation which allow healing of bony and soft-tissue problems. Fusing an infected joint is a safe procedure that allows maintaining functional capabilities.
Peri-Implant Fractures Around Hindfoot Fusion Nails: A Systematic Literature Review and Classification System
Authors: Velasco Brian T. , Briceno Jorge , Miller Christopher , Ye Michael Y. , Savage-Elliott Ian , Ellington J. Kent , Kwon John Y. 
Published: October 2019

Category: Hindfoot Introduction/Purpose: Tibio-talo calcaneal (TTC) arthrodesis is increasingly performed for hindfoot arthrosis and other indications. Peri-implant fracture around hindfoot fusion nails has been previously reported and can be problematic to treat given multiple surgical considerations including the status of hind foot arthrodesis at time of fracture. We present a systematic review of the literature regarding peri-implant fractures around hindfoot fusion nails and propose a classification system to help guide treatment based on findings from the current literature as well as the collective experience of the senior authors. Methods: A review of the literature was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify clinical investigations in which peri-implant fractures or other hardware failures were observed as complications following TTC arthrodesis using hindfoot nails by two research assistants. The electronic database of PubMed / Medline was explored using specific search terms, Boolean operators, and field tags. The same query without field tags and under “Search All Text” was used to explore the electronic database of the Cochrane Library. Inclusion criteria was any clinical investigation that reported on outcomes after TTC arthrodesis using a hindfoot nail in at least one patient. Cadaveric and non-clinical investigations were excluded. Manuscript language for both databases was restricted to the English literature. Results: A total of 36 studies were identified which met inclusion criteria and reported clinical outcomes after TTC arthrodesis using a hindfoot fusion nail. Of the 36 studies, there was a total of 13 intraoperative fractures, 43 tibial stress fractures and 24 peri-implant fractures recorded in 12 of the 36 studies. Conclusion: Peri-implant fracture following tibio-talo calcaneal arthrodesis using a hindfoot intramedullary nail is an uncommon but problematic condition to treat. General heterogeneity of patients and indications as well as a lack of descriptive detail in the current literature makes meta-analysis difficult. Given the lack of consensus on treatment, a classification system may be helpful to guide clinical practice.