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PURPOSE: Implant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage. METHODS: Six skeletally mature female sheep were randomly assigned (n = 3) to either the PMMA or the triphasic implant (AGN1, composition: calcium sulfate, ß-tricalcium phosphate, brushite) treatment group. Femoral veins of each sheep were directly injected with 0.5 mL of implant material to mimic leakage volumes reported during PMMA vertebroplasty. To compare acute systemic effects of the materials, cardiovascular parameters, laboratory coagulation markers, and calcium and sulfate serum levels were monitored for 60 min after implant injection. Thrombotic and embolic events were evaluated by radiologic imaging, necropsy, and histopathology. RESULTS: Heart rate, systemic arterial blood pressure, arterial oxygenation, arterial carbon dioxide content, and coagulation markers remained within physiological range after either AGN1 or PMMA injection. No blood flow interruption in the larger pulmonary vessels was observed in either group. Lung histopathology revealed that the severity of thrombotic changes after AGN1 injection was minimal to slight, while changes after PMMA injection were minimal to massive. CONCLUSION: Acute systemic effects of intravascular AGN1 appeared to be comparable to or less than that of intravascular PMMA. Furthermore, in this preliminary study, the severity and incidence of pulmonary histological changes were lower for AGN1 compared to PMMA.
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Embolia Pulmonar , Vertebroplastia , Animales , Cementos para Huesos , Calcio , Sulfato de Calcio , Dióxido de Carbono , Femenino , Polimetil Metacrilato , Ovinos , Vertebroplastia/métodosRESUMEN
OBJECTIVE: To provide a systematic assessment of the efficacy of preoperative skin asepsis using chlorhexidine versus povidone-iodine based protocols for surgical site infection (SSI) prevention in veterinary surgery. STUDY DESIGN: Systematic meta-analytical review according to PRISMA-P guidelines. SAMPLE POPULATION: Studies comparing preoperative skin asepsis protocols using chlorhexidine versus povidone-iodine in veterinary surgery identified by systematic search between 1990 and 2020. METHODS: A search using MEDLINE/Pubmed, Web of Science and CAB Abstracts was performed, followed by secondary searches of Google Scholar, Proquest Dissertation and Theses, and relevant bibliographic articles. Primary and secondary outcome measures were the efficacy of skin asepsis protocols using chlorhexidine versus povidone-iodine on SSI incidence and skin bacterial colonization, respectively. A meta-analysis was performed with a random-effect model, with effect size calculated as risk ratio (RR) or mean standard deviation (MSD) with 95% CI. Statistical significance was set at P < .05. RESULTS: Among 1067 publications that met the initial search criteria, 9 relevant studies were eligible for analysis. No difference in the incidence of postoperative SSI or skin bacterial colonization between preoperative asepsis protocols using chlorhexidine versus povidone-iodine was found. Insufficient information and detail were frequent among studies and precluded a clear assessment of bias. CONCLUSION: This study showed that asepsis protocols using chlorhexidine were comparable to povidone-iodine in preventing postoperative SSI and reducing skin bacterial colonization. CLINICAL SIGNIFICANCE: Given the limitations of the studies that were included in terms of both quality and quantity, more high-quality randomized controlled trials are needed to confirm these conclusions.
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Antiinfecciosos Locales , Povidona Yodada , Infección de la Herida Quirúrgica/veterinaria , Animales , Antiinfecciosos Locales/uso terapéutico , Asepsia , Clorhexidina/uso terapéutico , Protocolos Clínicos , Etanol/uso terapéutico , Metaanálisis como Asunto , Povidona Yodada/uso terapéutico , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/veterinaria , Cirugía Veterinaria , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
OBJECTIVE: To determine the influence of screw head diameter on equine condylar fracture fixation with 5.5 mm cortical screws. STUDY DESIGN: Ex vivo, biomechanical study, blinded, matched-pair design. SAMPLE POPULATION: Fifteen pairs of equine third metacarpal (MC3) bones. METHODS: Lateral condylar fractures were simulated by parasagittal osteotomies and repaired pairwise by 2 × 5.5 mm cortical screws of 8 mm (standard) or 10 mm (modified) head diameter. Interfragmentary compression at maximum screw insertion torque was measured. The instrumented specimens were pairwise stratified for biomechanical testing under the following modalities (n = 5): (1) screw insertion torque to failure, (2) quasi-static axial load to failure, and (3) cyclic axial load to 2 mm displacement followed by failure. Tests (1) and (2) were analyzed for yield, maximum, and failure torque/angle and load/displacement, respectively. Number of cycles to 2 mm displacement and failure was assessed from test (3). RESULTS: Maximum insertion torque was greater, and failure angle smaller, when constructs repaired with modified screws were tested (8.1 ± 0.5 vs. 7.4 ± 0.5 Nm; P = .0047 and 550 ± 104 vs. 1130 ± 230; P = .008). Axial yield (7118 ± 707 vs. 5740 ± 2267 N; P = .043) and failure load (12 347 ± 3359 vs. 8695 ± 2277 N; P = .043) were greater for specimens repaired with modified screws. No difference was detected between constructs in the number of cycles to 2 mm displacement. CONCLUSION: Condylar MC3 osteotomies repaired with modified 5.5 mm cortical screws sustained greater maximal hand torque insertion, smaller insertion failure angle and 1.4 fold greater quasi-static failure forces than constructs repaired with standard 5.5 mm screws. CLINICAL SIGNIFICANCE: Use of modified screws with larger heads may improve the fixation of condylar fractures in horses. These results provide evidence to justify clinical evaluation in horses undergoing fracture repair.
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Fracturas Óseas , Enfermedades de los Caballos , Animales , Fenómenos Biomecánicos , Tornillos Óseos/veterinaria , Cadáver , Fijación de Fractura/veterinaria , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/veterinaria , Fracturas Óseas/cirugía , Fracturas Óseas/veterinaria , Caballos/cirugía , TorqueRESUMEN
Background and Objectives: Fracture healing is currently assessed through qualitative evaluation of radiographic images, which is highly subjective in nature. Radiographs can only provide snapshots in time, which are limited due to logistics and radiation exposure. We recently proposed assessing the bone healing status through continuous monitoring of the implant load, utilizing an implanted sensor system, the Fracture Monitor. The device telemetrically transmits statistically derived implant parameters via the patient's mobile phone to assist physicians in diagnostics and treatment decision-making. This preclinical study aims to systematically investigate the device safety and performance in an animal setting. Materials and Methods: Mid-shaft tibial osteotomies of different sizes (0.6-30 mm) were created in eleven Swiss mountain sheep. The bones were stabilized with either a conventional Titanium or stainless-steel locking plate equipped with a Fracture Monitor. Data were continuously collected over the device's lifetime. Conventional radiographs and clinical CT scans were taken longitudinally over the study period. The radiographs were systematically scored and CTs were evaluated for normalized bone volume in the defect. The animals were euthanized after 9 months. The sensor output was correlated with the radiologic parameters. Tissue samples from the device location were histologically examined. Results: The sensors functioned autonomously for 6.5-8.4 months until energy depletion. No macroscopic or microscopic adverse effects from device implantation were observed. The relative implant loads at 4 and 8 weeks post-operation correlated significantly with the radiographic scores and with the normalized bone volume metric. Conclusions: Continuous implant load monitoring appears as a relevant approach to support and objectify fracture healing assessments and carries a strong potential to enable patient-tailored rehabilitation in the future.
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Placas Óseas , Fijación Interna de Fracturas , Animales , Curación de Fractura , Osteotomía , Ovinos , TitanioRESUMEN
Background and Objectives: Spinal fusion is an effective and widely accepted intervention. However, complications such as non-unions and hardware failures are frequently observed. Radiologic imaging and physical examination are still the gold standards in the assessment of spinal fusion, despite multiple limitations including radiation exposure and subjective image interpretation. Furthermore, current diagnostic methods only allow fusion assessment at certain time points and require the patient's presence at the hospital or medical practice. A recently introduced implantable sensor system for continuous and wireless implant load monitoring in trauma applications carries the potential to overcome these drawbacks, but transferability of the principle to the spine has not been demonstrated yet. Materials and Methods: The existing trauma sensor was modified for attachment to a standard pedicle-screw-rod system. Two lumbar segments (L2 to L4) of one Swiss white alpine sheep were asymmetrically instrumented. After facetectomy, three sensors were attached to the rods between each screw pair and activated for measurement. The sheep was euthanized 16 weeks postoperatively. After radiological assessment the spine was explanted and loaded in flexion-extension to determine the range of motion of the spinal segments. Sensor data were compared with mechanical test results and radiologic findings. Results: The sensors measured physiological rod loading autonomously over the observation period and delivered the data daily to bonded smartphones. At euthanasia the relative rod load dropped to 67% of the respective maximum value for the L23 segment and to 30% for the L34 segment. In agreement, the total range of motion of both operated segments was lower compared to an intact reference segment (L23: 0.57°; L34: 0.49°; intact L45: 4.17°). Radiologic assessment revealed fusion mass in the facet joint gaps and bilateral bridging bone around the joints at both operated segments. Conclusions: Observations of this single-case study confirm the basic ability of continuous rod load measurement to resolve the spinal fusion process as indicated by a declining rod load with progressing bone fusion. A strong clinical potential of such technology is eminent, but further data must be collected for final proof of principle.
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Enfermedades de la Columna Vertebral , Fusión Vertebral , Animales , Fenómenos Biomecánicos , Tornillos Óseos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Rango del Movimiento Articular/fisiología , Ovinos , Fusión Vertebral/métodosRESUMEN
OBJECTIVE: To determine the stability bovine stifles stabilized with nylon or nitinol superelastic prostheses after transection of the cranial cruciate ligament (CCL). STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Stifles (n = 15) harvested from adult bovine cadavers. METHODS: The stifles were randomly assigned pairwise to a ligament reconstruction technique (n = 5): (1) and (2) Hamilton's technique using a prosthesis made of 24 nitinol strands (0.39 mm) braided at 40°or single 600-lb test nylon implant, and (3) nitinol prosthesis placed in femoral and tibial bone tunnels (bone-to-bone). Craniocaudal tibial translation at ±2000 N was applied to the tibia, and mediolateral angular displacement via measured under torsional tibial loading at ±60 Nm on three occasions: intact CCL, transected, and stabilized. Outcomes were evaluated with a mixed effect linear model for repeated measures. RESULTS: Bone-to-bone using nitinol was the only repair that decreased tibial translation after CCL transection (p = .001) with a 23% change magnitude compared with intact CCL. Hamilton was the only stabilization reestablishing angular displacement, similar to intact CCL (p = .109 and .134 for nitinol and nylon). Bone-to-bone nitinol stabilization decreased angular displacement after CCL-transection with an 8% change magnitude (p = .040) without returning to normal values. CONCLUSION: CCL replacement with nylon did restore joint stability. Nitinol prostheses passed through single femoral and tibial bone tunnels (bone-to-bone) were the only techniques reducing tibial translation. CLINICAL SIGNIFICANCE/IMPACT: Bone-to-bone stabilization with a nitinol prosthesis may be considered as an alternative to nylon for CCL replacement in cattle. These results provide evidence to justify clinical evaluation in cattle undergoing CCL replacement.
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Lesiones del Ligamento Cruzado Anterior , Enfermedades de los Bovinos , Aleaciones , Animales , Ligamento Cruzado Anterior , Lesiones del Ligamento Cruzado Anterior/veterinaria , Fenómenos Biomecánicos , Cadáver , Bovinos , Prótesis e Implantes , Rodilla de Cuadrúpedos/cirugía , TibiaRESUMEN
OBJECTIVE: To report the clinical presentation, treatment, and outcome of cattle undergoing surgical extraction of apically infected cheek teeth (CT). STUDY DESIGN: Short case series. ANIMALS: Nine adult cattle. METHODS: Medical records were searched for cattle having a diagnosis of apical infection of CT that were treated with surgical extraction between 2005 and 2017. Data retrieved included clinical examination, ancillary tests, surgical procedure, and outcomes. RESULTS: The main presenting complaints were mandibular swelling and decreased appetite and milk production. In total, 7 mandibular and 3 maxillary CT were extracted, 7 molars and 3 premolars that were distributed more frequently on the left dental arcades (n = 7 CT). Two cattle had no visible external lesions. Radiograph images revealed that lucency surrounded all affected tooth roots. Mandibular teeth were removed by lateral buccotomy with removal of alveolar bone plate or retrograde repulsion, and maxillary teeth were removed by repulsion through a maxillary sinus flap. Most common bacterial isolates consisted of anaerobic bacteria (6/11 isolates) and Truperella pyogenes (3/11 isolates). The most common complications included inability to remove the tooth intact (n = 4 cattle) and surgical site infection (n = 5). All cattle remained in their herd after treatment. CONCLUSION: Surgical extraction of CT was achieved in all 9 cattle. The postoperative morbidity was high but without long-term consequences on animal productivity. CLINICAL SIGNIFICANCE: Surgical extraction of CT is a successful treatment for apical infection in cattle.
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Enfermedades de los Bovinos/cirugía , Periodontitis Periapical/veterinaria , Extracción Dental/veterinaria , Animales , Diente Premolar , Bovinos , Mandíbula , Maxilar , Diente Molar , Periodontitis Periapical/cirugía , Pronóstico , RadiografíaRESUMEN
A 2-year-old Holstein cow presented with a history of colic signs of 3 days' duration that had not responded to routine medical therapy. Physical examination findings were consistent with tachycardia and colic. Ultrasonographic examination of the abomasum revealed a thin hyperechoic line producing a cone shadow. Radiography of the cranial abdomen revealed two radiopaque objects within the abomasum. Right paracostal laparotomy and abomasotomy permitted palpation and manual removal of two metallic foreign bodies and a small quantity of gravel. The animal recovered well after surgery and no signs of colic were observed. Her appetite and rumination were also improved.
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Bovinos/lesiones , Cuerpos Extraños/veterinaria , Abomaso/diagnóstico por imagen , Abomaso/patología , Abomaso/cirugía , Animales , Bovinos/cirugía , Cólico/diagnóstico por imagen , Cólico/etiología , Cólico/cirugía , Cólico/veterinaria , Femenino , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Laparotomía/veterinariaRESUMEN
Two Holstein heifers were referred for non-weight bearing lameness. The physical examination and radiographic findings were diagnostic of tarsal luxation. Treatment and outcome are reported. A closed reduction was successfully performed in 1 heifer. The second animal was euthanized after attempts to reduce and stabilize the joint.
Luxations multiples du tarse chez 2 taures Holstein. Deux taures Holstein ont été référées pour boiterie de non-appuie. L'examen physique et les radiographies étaient diagnostiques d'une luxation du tarse. Les traitements et pronostic sont décrits. Une réduction fermée a été possible sur une taure et l'autre a été euthanasiée après l'échec de la réduction.(Traduit par les auteurs).
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Enfermedades de los Bovinos/patología , Luxaciones Articulares/veterinaria , Tarso Animal/patología , Animales , Bovinos , Enfermedades de los Bovinos/cirugía , Femenino , Luxaciones Articulares/patología , Cojera Animal/etiología , Cojera Animal/cirugía , Tarso Animal/cirugía , Resultado del TratamientoRESUMEN
Reliable and timely assessment of bone union between vertebrae is considered a key challenge after spinal fusion surgery. Recently, a novel sensor concept demonstrated the ability to objectively assess posterolateral fusion based on continuous implant load monitoring. The aim of this study was to investigate systematically the concept in a mono-segmental fusion model using an updated sensor setup. Three sheep underwent bilateral facetectomy at level L2-L3 and L4-L5. The segments were stabilized using two unconnected pedicle-screw-rod constructs per level. Sensing devices were attached to the rods between each pedicle screw pair and the loads were continuously monitored over 16 weeks. After euthanasia, the spines were biomechanically tested for their range of motion and high-resolution CT scans were performed to confirm the fusion success. After an initial increase in implant load until reaching a maximum (100 %) at approximately week 4, eleven out of twelve sensors measured a constant decrease in implant load to 52 ± 9 % at euthanasia. One sensor measurement was compromised by newly forming bone growing against the sensor clamp. Bridging bone at each facet and minor remnant segmental motion (<0.7°) confirmed the fusion of all motion segments. Data obtained by continuous measurement of implant loading of spinal screw-rod constructs enables objective monitoring of spinal fusion progression. The sensor concept provides valuable real-time information, offering quantifiable data as an alternative to traditional imaging techniques. However, the design of the current sensor concept needs to be matured, tailored to, and validated for the human spine.
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Tornillos Pediculares , Fusión Vertebral , Humanos , Animales , Ovinos , Vértebras Lumbares/cirugía , Fenómenos Biomecánicos , Rango del Movimiento ArticularRESUMEN
Orthopedic device-related infection (ODRI) preclinical models are widely used in translational research. Most ODRI models require induction of general anesthesia, which frequently results in hypothermia in rodents. This study aimed to evaluate the impact of peri-anesthetic hypothermia in rodents on outcomes in preclinical ODRI studies. A retrospective analysis of all rodents that underwent surgery under general anesthesia to induce an ODRI model with inoculation of Staphylococcus epidermidis between 2016 and 2020 was conducted. A one-way multivariate analysis of covariance (one-way MANCOVA) was used to determine the fixed effect of peri-anesthetic hypothermia (hypothermic defined as rectal temperature <35°C) on the combined harvested tissue and implant colony-forming unit (CFU) counts, and having controlled for the study groups including treatments received, duration of surgery and anesthesia, and study period. The results showed a significant effect of peri-anesthetic hypothermia on the post-mortem combined CFU counts from the harvested tissue and implant(s) (p = 0.01) when comparing normo- versus hypothermic rodents. Using Wilks' Λ as a criterion to determine the contribution of independent variables to the model, peri-anesthetic hypothermia was the most significant, though still a weak predictor, of increased harvested CFU counts. Altogether, the data corroborate the concept that bacterial colonization is affected by abnormal body temperature during general anesthesia at the time of bacterial inoculation in rodents, which needs to be taken into consideration to decrease infection data variability and improve experimental reproducibility.
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Anestesia , Anestésicos , Hipotermia , Humanos , Temperatura Corporal , Estudios Retrospectivos , Reproducibilidad de los Resultados , Anestésicos/farmacologíaRESUMEN
Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare. To determine the feasibility of autologous cancellous bone graft harvest from different anatomical donor sites (humerus, ilium, femur, tibia, and tail vertebrae) in rats and compare their suitability as donor sites, a total of 13 freshly euthanized rats were used to describe the surgical technique, determine the cancellous bone volume and microstructure, and compare the cancellous bone collected quantitatively and qualitatively. It was feasible to harvest cancellous bone grafts from all five anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis using micro-computed tomography showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested weight and volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of alkaline phosphatase and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. In conclusion, the tibia and iliac crest may be the most favorable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study.
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Trasplante Óseo , Hueso Esponjoso , Recolección de Tejidos y Órganos , Sitio Donante de Trasplante , Hueso Esponjoso/trasplante , Microtomografía por Rayos X , Ratas , Animales , Ilion/trasplante , Trasplante Autólogo , Trasplante Óseo/métodos , Estudios de Factibilidad , Fémur , Húmero , TibiaRESUMEN
AIM: Secondary bone healing requires an adequate level of mechanical stimulation expressed by the extent of interfragmentary motion in the fracture. However, there is no consensus about when the mechanical stimulation should be initiated to ensure a timely healing response. Therefore, this study aims to compare the effect of the immediate and delayed application of mechanical stimulation in a large animal model. METHODS: Twelve Swiss White Alpine sheep underwent partial osteotomy of a tibia that was stabilised with an active fixator inducing well-controlled mechanical stimulation. Animals were randomly assigned into two groups with different stimulation protocols. The immediate group received daily stimulation (1000â¯cycles/day) from the first day post-operation, while in the delayed group, stimulation began only on the 22nd day post-operation. Healing progression was evaluated daily by measuring the in vivo stiffness of the repair tissue and by quantifying callus area on weekly radiographs. All animals were euthanised five weeks post-op. Post-mortem callus volume was determined from high-resolution computer tomography (HRCT). RESULTS: Fracture stiffness (pâ¯<â¯0.05) and callus area (pâ¯<â¯0.01) were significantly larger for the immediate group compared to the delayed stimulation group. In addition, the callus volume measured on the post-mortem HRCT showed 319â¯% greater callus volume for the immediate stimulation group (pâ¯<â¯0.01). CONCLUSIONS: This study demonstrates that a delay in the onset of mechanical stimulation retards fracture callus development and that mechanical stimulation already applied in the early post-op phase promotes bone healing.
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Curación de Fractura , Fracturas Óseas , Animales , Fenómenos Biomecánicos , Callo Óseo , Modelos Animales de Enfermedad , Fijación de Fractura/métodos , Curación de Fractura/fisiología , OvinosRESUMEN
Background: Artificial intelligence is a revolutionary technology that promises to assist clinicians in improving patient care. In radiology, deep learning (DL) is widely used in clinical decision aids due to its ability to analyze complex patterns and images. It allows for rapid, enhanced data, and imaging analysis, from diagnosis to outcome prediction. The purpose of this study was to evaluate the current literature and clinical utilization of DL in spine imaging. Methods: This study is a scoping review and utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to review the scientific literature from 2012 to 2021. A search in PubMed, Web of Science, Embased, and IEEE Xplore databases with syntax specific for DL and medical imaging in spine care applications was conducted to collect all original publications on the subject. Specific data was extracted from the available literature, including algorithm application, algorithms tested, database type and size, algorithm training method, and outcome of interest. Results: A total of 365 studies (total sample of 232,394 patients) were included and grouped into 4 general applications: diagnostic tools, clinical decision support tools, automated clinical/instrumentation assessment, and clinical outcome prediction. Notable disparities exist in the selected algorithms and the training across multiple disparate databases. The most frequently used algorithms were U-Net and ResNet. A DL model was developed and validated in 92% of included studies, while a pre-existing DL model was investigated in 8%. Of all developed models, only 15% of them have been externally validated. Conclusions: Based on this scoping review, DL in spine imaging is used in a broad range of clinical applications, particularly for diagnosing spinal conditions. There is a wide variety of DL algorithms, database characteristics, and training methods. Future studies should focus on external validation of existing models before bringing them into clinical use.
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Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9-30 and MK.R3-15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future.
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Bacteriófagos , Infecciones por Pseudomonas , Animales , Ratones , Pseudomonas aeruginosa , Meropenem/uso terapéutico , Alginatos , Microesferas , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/uso terapéutico , BiopelículasRESUMEN
Background: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model. Methods: Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose-methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology. Results: All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion. Conclusions: All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.
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OBJECTIVE: To determine the prognostic value of lactate concentration measurements at admission in cattle with long-bone fractures. ANIMALS: 43 cattle with long-bone fractures between July 2016 and Dec 2018. PROCEDURES: In this prospective cohort study, lactate concentration was measured in systemic venous blood and locally in capillary blood sampled from the fractured and contralateral limbs of cattle and assessed for outcome prediction. The cutoff value was determined by maximizing the Youden index from receiver-operating characteristic curves. Multivariable logistic regression was employed to verify whether higher lactate concentrations compared with the cutoff value were an independent risk factor for poor outcomes at 30 days or 3 years after admission. RESULTS: Poor outcome was associated with higher capillary lactate concentration in the fractured limb (P < .001) and greater difference with systemic blood (P = .005). A cutoff value of lactate difference ≥ 2.4 mmol/L (sensitivity = 0.80; specificity = 0.965) between capillary lactate in the fractured limb and systemic blood was the best predictor of death ≤ 30 days after admission (P < .001). Multivariable analysis revealed that this cutoff value was an independent risk factor for 30-day and 3-year outcomes (P < .001). CLINICAL RELEVANCE: Admission blood lactate concentration difference ≥ 2.4 mmol/L between the fractured limb and systemic blood was a robust and independent predictor of outcome for cattle of the present report. Lactate metabolism is locally impaired in fractured limbs of nonsurviving or at higher complication risk cattle, which may help identify patients at high risk for poor outcomes.
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Enfermedades de los Bovinos , Fracturas Óseas , Bovinos , Animales , Ácido Láctico , Estudios Prospectivos , Pronóstico , Curva ROC , Fracturas Óseas/complicaciones , Fracturas Óseas/veterinariaRESUMEN
Background: The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare in vivo IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies. Methods: Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box-cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre- and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading). Results: All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box-cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box-cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height. Conclusions: The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.
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Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/- myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC-bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1ß, TNFα, IL-10, and TGF-ß. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections.
RESUMEN
Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need for novel strategies to prevent these serious infections that do not involve conventional antibiotics. Recently, a novel antibiofilm coating for titanium surfaces was developed based on 5-(4-bromophenyl)-N-cyclopentyl-1-octyl-1H-imidazol-2-amine as an active biofilm inhibitor. In the current study we present an optimized coating protocol that allowed for a 5-fold higher load of this active compound, whilst shortening the manufacturing process. When applied to titanium disks, the newly optimized coating was resilient to the most common sterilization procedures and it induced a 1 log reduction in biofilm cells of a clinical Staphylococcus aureus isolate (JAR060131) in vitro, without affecting the planktonic phase. Moreover, the antibiofilm effect of the coating in combination with the antibiotic cefuroxime was higher than cefuroxime treatment alone. Furthermore, the coating was successfully applied to a human-scale fracture fixation device resulting in a loading that was comparable to the titanium disk model. Finally, an in vivo biocompatibility and healing study in a rabbit osteotomy model indicated that these coated implants did not negatively affect fracture healing or osteointegration. These findings put our technology one step closer to clinical trials, confirming its potential in fighting orthopedic infections without compromising healing.