What a Ratchet! A Gripping Case Report of an Entrapped Finger with an Unyielding Wrench.

Finger entrapment with rings or ring-like objects is an uncommon possible hand emergency. In cases in which noncutting removal is ineffective, ring cutters or dental drills with carbide or diamond burs have been successfully used. However, objects composed of hard metallic alloys, such as lug nuts or wrenches, are often resistant to such equipment. In these instances, larger diameter metal cutting burrs or rasps may be more advantageous. Due to their increased size and cutting power, these tools are better suited to handle the toughness of hard metals. In this case report, we present the effective and efficient removal of a stainless steel wrench from an entrapped digit using a helicoidal rasp. Availability of this instrument within orthopedic departments may prevent the delays often described in the treatment of finger entrapment when traditional cutting equipment fails.

Intraoperative Anaphylaxis to Gelatin during Alveolar Bone Grafting for Cleft Palate.

Intraoperative anaphylaxis can be life threatening. Anaphylaxis to gelatin-based topical hemostatic agents is an underrecognized hypersensitivity. To date, only 21 cases of intraoperative anaphylaxis have been reported for gelatin-based hemostatic agents. In this article, we report the case of a 10-year-old male patient who sustained anaphylaxis after the use of Gelfoam during harvest of a bone graft. Rapid diagnosis and treatment of intraoperative anaphylaxis is imperative to prevent adverse outcomes. Referral to an allergist for identification of the allergen and appropriate notation in the medical record are paramount to avoid future anaphylactic events. Surgeons should avoid gelatin-based hemostatic agents, such as Gelfoam, in patients with reported intolerance of gelatin-based foods and medicines.

Repair of an Occipital Meningocele and Scalp Soft-tissue Reconstruction in a Newborn Patient.

The differential diagnosis of large congenital scalp defects includes aplasia cutis and encephalocele, among others. Treatment includes conservative management with dressings or operative management with dermal substitutes, skin grafting, local flaps, and free flaps. This case report discusses the technical considerations and reconstructive strategies for repair of a meningocele in a newborn with a large 5.5-cm scalp defect. The key strategies include preemptive cerebrospinal fluid (CSF) diversion with external ventricular drain to reduce the risk of CSF leak and mitigate wound-healing complications; careful identification and avoidance of key anatomic structures, such as the superior sagittal sinus, as anatomy may be significantly distorted due to the presence of a meningocele and after CSF diversion; and careful, thoughtful design of the local scalp flaps to maximize blood supply and to avoid tension on the final reconstruction.

Bilateral Distal Radius Fractures in a Patient with Osteogenesis Imperfecta: A Case Report.

CASE: Longitudinal follow-up of a 53-year-old woman with osteogenesis imperfecta (OI) Type III and concurrent bilateral distal radius fractures is reported. She had a right-sided displaced fracture and a left-sided minimally displaced fracture. Operative management of the displaced fracture showed adequate healing in 10 weeks. The minimally displaced fracture failed nonoperative management but did adequately heal after operative intervention. CONCLUSION: Early surgical intervention of distal radius fractures may be considered in patients with severe OI, even in fractures with minimal displacement. This is likely particularly important with patients who are heavily reliant on their upper extremities for mobility.

Quantitative Evaluation of Equine Articular Cartilage Using Cationic Contrast-Enhanced Computed Tomography.

OBJECTIVE: To investigate the diffusion trajectory of a cationic contrast medium (CA4+) into equine articular cartilage, and to assess normal and degenerative equine articular cartilage using cationic contrast-enhanced computed tomography (CECT). DESIGN: In the first experiment (Exp1), equine osteochondral specimens were serially imaged with cationic CECT to establish the diffusion time constant and time to reach equilibrium in healthy articular cartilage. In a separate experiment (Exp2), articular cartilage defects were created on the femoral trochlea (defect joint) in a juvenile horse, while the opposite joint was a sham-operated control. After 7 weeks, osteochondral biopsies were collected throughout the articular surfaces of both joints. Biopsies were analyzed for cationic CECT attenuation, glycosaminoglycan (GAG) content, mechanical stiffness (Eeq), and histology. Imaging, biochemical and mechanical data were compared between defect and control joints. RESULTS: Exp1: The mean diffusion time constant was longer for medial condyle cartilage (3.05 ± 0.1 hours) than lateral condyle cartilage (1.54 ± 0.3 hours, P = 0.04). Exp2: Cationic CECT attenuation was lower in the defect joint than the control joint (P = 0.005) and also varied by anatomic location (P = 0.045). Mean cationic CECT attenuation from the lateral trochlear ridge was lower in the defect joint than in the control joint (2223 ± 329 HU and 2667 ± 540 HU, respectively; P = 0.02). Cationic CECT attenuation was strongly correlated with both GAG (ρ = 0.79, P < 0.0001) and Eeq (ρ = 0.61, P < 0.0001). CONCLUSIONS: The equilibration time of CA4+ into equine articular cartilage is affected by tissue volume. Quantitative cationic CECT imaging reflects the biochemical, biomechanical and histological state of normal and degenerative equine articular cartilage.

dGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage.

Magnetic resonance imaging (MRI) and computed tomography (CT) are widely used to image cartilage and their diagnostic capability is enhanced in the presence of contrast agents. The aim of the study is to directly compare the performance between commercial anionic MRI (Gd(DTPA), Gd2-) and CT (Ioxaglate, Iox1-) contrast agents with novel cationic MRI (Gd(DTPA)Lys2 , Gd4+) and CT (CA4+) contrast agents for assessment of cartilage mechanical and biochemical properties using the ex vivo human osteoarthritis metacarpal cartilage model. First, indentation testing was conducted to obtain the compressive modulus of the human fifth metacarpals. The samples were then immersed in the anionic and cationic contrast agents prior to delayed gadolinium-enhanced MRI of cartilage and CT scanning, respectively. The cartilage glycosaminoglycan (GAG) content and distribution were determined using the 1,9-dimethylmethylene blue assay and Safranin-O histology. Cationic agents significantly accumulate in cartilage compared with anionic agents. Significant positive correlations (p < 0.05) exist between imaging results of cationic agents and GAG content (Gd4+: R2 = 0.43; CA4+: R2 = 0.67) and indentation equilibrium modulus (Gd4+: R2 = 0.48; CA4+: R2 = 0.77). Significant negative correlations are observed between anionic MRI relaxation times, but not contrast-enhanced computed tomography attenuation and cartilage GAG content (Gd2-: R2 = 0.56, p < 0.05; Iox1-: R2 = 0.31, p > 0.05) and indentation equilibrium modulus (Gd2-: R2 = 0.38, p < 0.05; Iox1-: R2 = 0.17, p > 0.05). MRI or CT with cationic contrast agents provides greater sensitivity than their anionic analogs at assessing the biochemical and biomechanical properties of ex vivo human metacarpal cartilage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:719-725, 2020.

A Synthetic Bottle-brush Polyelectrolyte Reduces Friction and Wear of Intact and Previously Worn Cartilage.

A poly(7-oxanorbornene-2-carboxylate) polymer containing pendent triethyleneglycol (TEG) chains of 2.8 MDa ("2.8M TEG") was synthesized and evaluated for long-term lubrication and wear reduction of ex vivo bovine cartilage as well as for synovitis in rats and dogs after intra-articular administration. Bovine cartilage surfaces were tested under torsional friction for 10,080 rotations while immersed in either saline, bovine synovial fluid (BSF), or 2.8M TEG. For each solution, coefficient of friction (µ), changes in surface roughness, and lost cartilage glycosaminoglycan were compared. To directly compare 2.8M TEG and BSF, additional samples were tested sequentially in BSF, BSF, 2.8M TEG, and then BSF. Finally, another set of samples were tested twice in saline to induce surface roughness and then tested in BSF, Synvisc, or 2.8M TEG to determine each treatment's effect on worn cartilage. Next, male Lewis rats were injected in one knee with 2.8M TEG or saline and evaluated for effects on gait, and female beagles were injected with either 2.8M TEG or saline in one knee, and their synovial tissues analyzed for inflammation by H&E staining. Treatment with 2.8M TEG lowers µ, lessens surface roughness, and minimizes glycosaminoglycan loss compared to saline. The 2.8M TEG also reduces µ compared to BSF in pairwise testing and on worn cartilage surfaces. Injection of 2.8M TEG in rat or beagle knees gives comparable effects to treatment with saline, and does not cause significant synovitis.

Contrast-Enhanced Computed Tomography Scoring System for Distinguishing Early Osteoarthritis Disease States: A Feasibility Study.

Early detection of osteoarthritis (OA) remains a diagnostic challenge owing to insensitive diagnostic techniques currently available. Herein a new semiquantitative scoring system, based upon contrast-enhanced computed tomographic (CECT) imaging, is described for further refinement of early OA disease staging. Trochlear ridge cartilage defects were surgically created in the femoropatellar joint of an adult horse (ACUC approved protocols). Seven weeks post-surgery, CECT imaging was performed on a clinical scanner after intra-articular injection of a cationic iodinated contrast agent, CA4+, into both injured and control femoropatellar joint compartments. The femoral cartilage surface was densely biopsied, and specimens were assessed for visual (Outerbridge score), functional (equilibrium compressive modulus), and biochemical (glycosaminoglycan content) measures of cartilage quality. Cartilage CECT attenuation was compared with cartilage quality measures using receiver operating characteristic curve analysis to establish attenuation thresholds for distinguishing among cartilage quality levels. CECT imaging identifies macroscopically damaged cartilage regions and in morphologically identical tissue provides moderately sensitive and specific semiquantitative segregation of cartilage quality based upon CECT attenuation, reflecting both glycosaminoglycan content and compressive stiffness of cartilage area under the curve (AUC = 0.83 [95% confidence interval [CI]: 0.72-0.93] for distinguishing poor quality and AUC = 0.76 [95% CI: 0.65-0.90] for distinguishing healthy quality cartilage). A semiquantitative 6-point scoring system-the Osteoarthritis Attenuation and Morphological Assessment (OAMA) score-is proposed as a tool for assessing cartilage quality from CECT images. The OAMA scoring system expands the current disease staging capability of early OA by inclusion of morphological, biochemical, and biomechanical assessments. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2138-2148, 2019.

Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

Murine articular cartilage morphology and compositional quantification with high resolution cationic contrast-enhanced µCT.

Articular cartilage lines the load-bearing surfaces of long bones and undergoes compositional and structural degeneration during osteoarthritis progression. Contrast enhanced microcomputed tomography (µCT) is being applied to a variety of preclinical models, including the mouse, to map structural and compositional properties in 3-D. The thinness (∼30-50 µm) and high cellularity of mouse articular cartilage presents a significant imaging challenge. Our group previously showed that mouse articular cartilage and proteoglycan (PG) content can be assessed by µCT with the ioxagalate-based contrast agent Hexabrix, but the voxel size used (6 µm) was deemed to be barely adequate. The objective of the present study is to assess the utility of a novel contrast agent, CA4+, to quantify mouse articular cartilage morphology and composition with high resolution µCT imaging (3 µm voxels) and to compare the sensitivity of CA4+ and Hexabrix to detect between-group differences. While both contrast agents are iodine-based, Hexabrix is anionic and CA4+ is cationic so they interact differently with negatively charged PGs. With CA4+, a strong correlation was found between non-calcified articular cartilage thickness measurements made with histology and µCT (R2 = 0.72, p < 0.001). Cartilage degeneration-as assessed by loss in volume, thickness, and PG content-was observed in 34-week-old mice when compared to both 7- and 12-week-old mice. High measurement precision was observed with CA4+, with the coefficient of variation after repositioning and re-imaging samples equaling 2.8%, 4.5%, 7.4% and 5.9% for attenuation, thickness, volume, and PG content, respectively. Use of CA4+ allowed increased sensitivity for assessing PG content compared to Hexabrix, but had no advantage for measurement of cartilage thickness or volume. This improvement in imaging should prove useful in preclinical studies of cartilage degeneration and regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2740-2748, 2017.

Contrast-enhanced CT imaging as a non-destructive tool for ex vivo examination of the biochemical content and structure of the human meniscus.

The biochemical and histopathological techniques used to investigate meniscal content and structure are destructive and time-consuming. Therefore, this study evaluated whether contrast-enhanced computed tomography (CECT) attenuation and contrast agent flux using the iodinated contrast agents CA4+ and ioxaglate correlate with the glycosaminoglycan (GAG) content/distribution and water content in human menisci. The optimal ioxaglate and CA4+ contrast agent concentrations for mapping meniscal GAG distribution were qualitatively determined by comparison of CECT color maps with Safranin-O stained histological sections. The associations between CECT attenuation and GAG content, CECT attenuation and water content, and flux and water content at various time points were determined using both contrast agents. Depth-wise analyses were also performed through each of the native surfaces to examine differences in contrast agent diffusion kinetics and equilibrium partitioning. The optimal concentrations for GAG depiction for ioxaglate and CA4+ were ≥80 and 12 mgI/ml, respectively. Using these concentrations, weak to moderate associations were found between ioxaglate attenuation and GAG content at all diffusion time points (1-48 h), while strong and significant associations were observed between CA4+ attenuation and GAG content as early as 7 h (R2 ≥ 0.67), being strongest at the equilibrium time point (48 h, R2 = 0.81). CECT attenuation for both agents did not significantly correlate with water content, but CA4+ flux correlated with water content (R2 = 0.56-0.64). CECT is a promising, non-destructive imaging technique for ex vivo assessment of meniscal GAG concentration and water content compared to traditional biochemical and histopathological methods. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1018-1028, 2017.

Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus.

Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.

Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes.

For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers--polycaprolactone and poly(glycerol monostearate-co-caprolactone)--to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ∼90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection.

Contrast-enhanced CT using a cationic contrast agent enables non-destructive assessment of the biochemical and biomechanical properties of mouse tibial plateau cartilage.

Mouse models of osteoarthritis (OA) are commonly used to study the disease's pathogenesis and efficacy of potential treatments. However, measuring the biochemical and mechanical properties of articular cartilage in these models currently requires destructive and time-consuming histology and mechanical testing. Therefore, we examined the feasibility of using contrast-enhanced CT (CECT) to rapidly and non-destructively image and assess the glycosaminoglycan (GAG) content. Using three ex vivo C57BL/6 mouse tibial plateaus, we determined the time required for the cationic contrast agent CA4+ to equilibrate in the cartilage. The whole-joint coefficient of friction (µ) of 10 mouse knees (some digested with Chondroitenase ABC to introduce variation in GAG) was evaluated using a modified Stanton pendulum. For both the medial and lateral tibial plateau cartilage of these knees, linear regression was used to compare the equilibrium CECT attenuations to µ, as well as each side's indentation equilibrium modulus (E) and Safranin-O determined GAG content. CA4+ equilibrated in the cartilage in 30.9 ± 0.95 min (mean ± SD, tau value of 6.17 ± 0.19 min). The mean medial and lateral CECT attenuation was correlated with µ (R(2) = 0.69, p < 0.05), and the individual medial and lateral CECT attenuations correlated with their respective GAG contents (R(2) ≥ 0.63, p < 0.05) and E (R(2) ≥ 0.63, p < 0.05). In conclusion, CECT using CA4+ is a simple, non-destructive technique for three-dimensional imaging of ex vivo mouse cartilage, and significant correlations between CECT attenuation and GAG, E, and µ are observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1130-1138, 2016.

Layered superhydrophobic meshes for controlled drug release.

Layered superhydrophobic electrospun meshes composed of poly(ε-caprolactone) (PCL) and poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) are described as a local source of chemotherapeutic delivery. Specifically, the chemotherapeutic agent SN-38 is incorporated into a central 'core' layer, between two 'shield' layers of mesh without drug. This mesh is resistant to wetting of the surface and throughout the bulk due to the pronounced hydrophobicity imparted by the high roughness of a hydrophobic polymer, PGC-C18. In serum solution, these meshes exhibit slow initial drug release over 10days corresponding to media infiltrating the shield layer, followed by steady release over >30days, as the drug-loaded core layer is wetted. This sequence of events is supported by X-ray computed tomography imaging of a contrast agent solution infiltrating the mesh. In vitro cytotoxicity data collected with Lewis Lung Carcinoma (LLC) cells are consistent with this release profile, remaining cytotoxic for over 20days, longer than the unlayered version. Finally, after subcutaneous implantation in rats, histology of meshes with and without drug demonstrated good integration and lack of adverse reaction over 28days. The drug release rates, robust superhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key design parameters for the development of an implantable chemotherapeutic-loaded device for the prevention of local lung cancer recurrence following surgical resection.

A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage.

A new cationic gadolinium contrast agent is reported for delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC). The agent partitions into the glycosaminoglycan rich matrix of articular cartilage, based on Donnan equilibrium theory, and its use enables imaging of the human cadaveric metacarpal phalangeal joint.

Tantalum oxide nanoparticles for the imaging of articular cartilage using X-ray computed tomography: visualization of ex vivo/in vivo murine tibia and ex vivo human index finger cartilage.

The synthesis and characterization of tantalum oxide (Ta2O5) nanoparticles (NPs) as new X-ray contrast media for microcomputed tomography (µCT) imaging of articular cartilage are reported. NPs, approximately 5-10 nm in size, and possessing distinct surface charges, were synthesized using phosphonate (neutral), ammonium (cationic), and carboxylate (anionic) ligands as end functional groups. Assessment of a cartilage defect in a human cadaver distal metacarpophalangeal (MCP) joint with the ammonium nanoparticles showed good visualization of damage and preferential uptake in areas surrounding the defect. Finally, an optimized nontoxic cationic NP contrast agent was evaluated in an in vivo murine model and the cartilage was imaged. These nanoparticles represent a new type of contrast agent for imaging articular cartilage, and the results demonstrate the importance of surface charge in the design of nanoparticulate agents for targeting the surface or interior zones of articular cartilage.

Bone-crack detection, targeting, and repair using ion gradients.

Bone cracks can be detected by utilizing the damaged matrix itself as both the trigger and the fuel. A crack in a material with a high mineral content such as bone generates ion gradients, which can be utilized for active targeting and treatment. This approach to targeting a biological structure augments current methods, which are focused on biomacromolecular interactions involving proteins and nucleic acids.

Contrast enhanced CT attenuation correlates with the GAG content of bovine meniscus.

We determined whether contrast-enhanced computed tomography (CECT) attenuation obtained using a µCT scanner correlated with the glycosaminoglycan (GAG) content and distribution in ex vivo bovine menisci. Bovine samples were immersed in different concentrations of the contrast agents CA4+ and Ioxaglate, and the µCT images were compared to Safranin-O staining. CA4+ and Ioxaglate diffusion-in kinetics and the correlation between their CECT attenuations and GAG content were investigated. CA4+ and Ioxaglate both reached steady state in the meniscal regions within 95 h, with tau values of 20.6 ± 3.98 and 25.9 ± 3.71 h (mean ± SD), respectively. Both agents diffused preferentially through the proximal and secondarily through the distal surface. The CA4+ CECT attenuation was strongly and positively correlated with the GAG content of the meniscus regions (R(2) = 0.89, p < 0.001) at low concentrations (12 mgI/ml), while the Ioxaglate CECT attenuation was moderately and negatively correlated with the GAG content (R(2) = 0.51, p = 0.03) at 60 mgI/ml. CECT can image ex vivo menisci, and the CA4+, compared to Ioxaglate, enhanced attenuation strongly correlates with the GAG content and distribution in bovine meniscus.

A Mechanistic Study of Wetting Superhydrophobic Porous 3D Meshes.

Superhydrophobic, porous, 3D materials composed of poly( ε -caprolactone) (PCL) and the hydrophobic polymer dopant poly(glycerol monostearate- co- ε -caprolactone) (PGC-C18) are fabricated using the electrospinning technique. These 3D materials are distinct from 2D superhydrophobic surfaces, with maintenance of air at the surface as well as within the bulk of the material. These superhydrophobic materials float in water, and when held underwater and pressed, an air bubble is released and will rise to the surface. By changing the PGC-C18 doping concentration in the meshes and/or the fiber size from the micro- to nanoscale, the long-term stability of the entrapped air layer is controlled. The rate of water infiltration into the meshes, and the resulting displacement of the entrapped air, is quantitatively measured using X-ray computed tomography. The properties of the meshes are further probed using surfactants and solvents of different surface tensions. Finally, the application of hydraulic pressure is used to quantify the breakthrough pressure to wet the meshes. The tools for fabrication and analysis of these superhydrophobic materials as well as the ability to control the robustness of the entrapped air layer are highly desirable for a number of existing and emerging applications.