A preliminary safety assessment of vertebral augmentation with32P brachytherapy bone cement.

Comprehensive treatment for vertebral metastatic lesions commonly involves vertebral augmentation (vertebroplasty or kyphoplasty) to relieve pain and stabilize the spine followed by multiple sessions of radiotherapy. We propose to combine vertebral augmentation and radiotherapy into a single treatment by adding32P, aß-emitting radionuclide, to bone cement, thereby enabling spinal brachytherapy to be performed without irradiating the spinal cord. The goal of this study was to address key dosimetry and safety questions prior to performing extensive animal studies. The32P was in the form of hydroxyapatite powder activated by neutron bombardment in a nuclear reactor. We performedex vivodosimetry experiments to establish criteria for safe placement of the cement within the sheep vertebral body. In anin vivostudy, we treated three control ewes and three experimental ewes with brachytherapy cement containing 2.23-3.03 mCi32P ml-1to identify the preferred surgical approach, to determine if32P leaches from the cement and into the blood, urine, or feces, and to identify unexpected adverse effects. Ourex vivoexperiments showed that cement with 4 mCi32P ml-1could be safely implanted in the vertebral body if the cement surface is at least 4 mm from the spinal cord in sheep and 5 mm from the spinal cord in humans.In vivo, a lateral retroperitoneal surgical approach, ventral to the transverse processes, was identified as easy to perform while allowing a safe distance to the spinal cord. The blood, urine, and feces of the sheep did not contain detectable levels of32P, and the sheep did not experience any neurologic or other adverse effects from the brachytherapy cement. These results demonstrate, on a preliminary level, the relative safety of this brachytherapy cement and support additional development and testing.

Multiple Venous Thromboembolism Pharmacologic Agents Are Associated with an Increased Risk for Early Postoperative Complications following a Total Joint Arthroplasty.

The purpose of this study was to determine the effect that concurrent venous thromboembolism (VTE) medications had on early outcomes following primary total joint arthroplasty (TJA). 2653 total knee and hip arthroplasties were reviewed at a tertiary medical center. The study performed a multivariable comparison of outcomes in patients on 2 or more VTE medications, as well as a logistic regression on outcomes following each addition of a VTE medication postoperatively (number of VTE medications was 1-4). Controlling for gender, age, body mass index, and preoperative American Society of Anesthesiologists score throughout the analysis, patients who received 2 or more VTE prophylaxis medications had increased LOS (p < 0.001), transfusions (p < 0.001), emergency department visits (p=0.001), readmissions (p < 0.001), 90dPOE (p < 0.001), and PE (p < 0.001). Every additional postoperative VTE medication incrementally increased the risk for longer LOS (p < 0.001), transfusions (p < 0.001), 90dPOE (p < 0.001), deep vein thrombosis (p=0.049), PE (p < 0.001), emergency department visits (p=0.005), and readmission (p=0.010). Patients on multiple VTE medications following TJA demonstrate significantly poorer outcomes. The current study's findings caution the use of multiple VTE medications whenever possible immediately following a TJA.

Comparison of Area Deprivation Index, Socioeconomic Parameters, and Preoperative Demographics With Postoperative Emergency Department Visits After Total Knee Arthroplasty.

BACKGROUND: This study aims to determine if socioeconomic (SE) parameters, primarily area deprivation index (ADI), relate to postoperative emergency department (ED) visits after total knee arthroplasty (TKA). METHODS: We retrospectively reviewed 2655 patients who underwent TKA in a health system of 4 hospitals. The primary outcome was an ED visit within 90 days, which was divided into those with and without readmission. SE parameters including ADI as well as preoperative demographics were analyzed. Univariable and multiple logistic regressions were performed determining risk of 90-day postoperative ED visits, as well as once in the ED, risks for readmission. RESULTS: 436 patients (16.4%) presented to the ED within 90 days. ADI was not a risk factor. The multiple logistic regression demonstrated men, Medicare or Medicaid, and preoperative ED visits were consistently risk factors for a postoperative ED visit with and without readmission. Preoperative anticoagulation was only a risk factor for ED visits with readmission. Among patients who visited the ED, if the patient was Caucasian, a lower BMI, or higher American Society of Anesthesiologists score, they were likely to be readmitted. CONCLUSION: The study demonstrated that the percentage of early ED returns after TKA was high and that ADI was not a predictor for 90-day postoperative ED visit. The only SE factor that may contribute to this phenomenon was insurance type. Once in the ED, race, preoperative ED visits, preoperative anticoagulation, BMI, gender, and preoperative American Society of Anesthesiologists score contributed to a risk of readmission. The study supports hospitals' mission to provide equal access health care.

Radiographic Predictors of Screw Cutout for Intertrochanteric Fractures Treated With Cephalomedullary Nails.

The objective of this study was to determine the predictive value of tip-apex distance (TAD) and Parker's ratio for screw cutout after treatment of intertrochanteric hip fractures with a long cephalomedullary nail. A total of 97 patients with AO/OTA 31-A1-A3 intertrochanteric fractures and a minimum follow-up of 8 weeks were included. Increased Parker's ratio on the anteroposterior radiograph (OR = 1.386, p < .003) and lateral radiograph (OR = 1.138, p < .028) was significantly associated with screw cutout. In a multivariable regression analysis, only the Parker's anteroposterior ratio was significantly associated with risk of screw cutout (OR = 1.393, p = .004), but TAD (OR = 0.977, p = .764) and Parker's lateral ratio (OR 1.032, p = .710) were not independent predictors of cutout. The study concluded that Parker's anteroposterior ratio is the most helpful measurement in predicting screw cutout. (Journal of Surgical Orthopaedic Advances 28(2):115-120, 2019).

Effect of Acetylsalicylic Acid Dose and Time Discontinued Preoperatively on Outcomes After Total Knee and Hip Arthroplasty.

The purpose of this study was to determine if acetylsalicylic acid (ASA) dose or time discontinued preoperatively affected surgical outcomes in total joint arthroplasty (TJA). The authors hypothesized that ASA worsens surgical outcomes in patients receiving higher doses and in those who discontinue ASA closer to the operative date. A total of 2853 TJAs (1802 primary total knee arthroplasties and 1051 total hip arthroplasties) performed at a tertiary medical center were reviewed. Postoperative outcomes of patients receiving ASA prior to TJA, dosing of ASA (81 mg or 325 mg) preoperatively and postoperatively, and the time of preoperative discontinuation (no ASA, <4 days, <7 days, and 7 or more days) were compared. Preoperative ASA was a risk factor for readmission (odds ratio [OR], 1.86; P<.001) and 90-day postoperative events (OR, 1.26; P=.004). Among patients receiving ASA, the dose was not a risk factor for any of the studied outcomes. Discontinuing ASA 7 or more days prior to TJA was protective for hematomas (OR, 0.64; P=.038), emergency department visits (OR, 0.79; P=.006), readmission (OR, 0.65; P<.001), and 90-day postoperative events (OR, 0.72; P<.001). These outcomes had a time effect: the risk was greater for those who discontinued therapy closer to the operative date. Patients who discontinued ASA 7 or more days prior to TJA had a lower incidence of hematomas, emergency department visits, readmissions, and 90-day postoperative events. This study's findings support discontinuing ASA at least 7 days prior to TJA. [Orthopedics. 2019; 42(5):286-293].

Short Versus Long Cephalomedullary Nails for Pertrochanteric Hip Fracture.

This study compared patients who underwent treatment with short or long cephalomedullary nails with integrated cephalocervical screws and linear compression. Patients with AO/OTA 31-A2 or A3 pertrochanteric fractures treated with either short (n=72) or long (n=97) InterTAN (Smith & Nephew, Memphis, Tennessee) cephalomedullary nails were reviewed. Information on perioperative measures (estimated blood loss, surgical time, and fluoroscopy time) and postoperative orthopedic complications (infection, implant failure, screw cutout, and periprosthetic femur fracture) was included. Estimated blood loss (short nail, 161 mL; long nail, 208 mL; P=.002) and surgical time (short nail, 64 minutes; long nail, 83 minutes; P=.001) were lower in the short nail group. There were no differences in fluoroscopy time (short nail, 90 seconds; long nail, 142 seconds; P=.071) or rates of infection (short nail, 1.4%; long nail, 3.1%; P=.637) or overall orthopedic complications (short nail, 11.1%; long nail, 9.3%; P=.798) between the 2 groups. The long nail group had a trend toward more screw cutouts (long nail, 5.2%; short nail, 0.0%; P=.134) but fewer periprosthetic femur fractures (short nail, 8.3%; long nail, 0.0%; P=.013). This study found a similar overall rate of orthopedic complications between short and long nails with integrated cephalocervical screws and linear compression. These results confirm the suspected advantages of short nails, including faster surgery and less blood loss; however, the rate of periprosthetic femur fracture remains high, despite changes to implant design. [Orthopedics. 2017; 40(2):83-88.].

Rivaroxaban Versus Enoxaparin for Venous Thromboembolism Prophylaxis after Hip and Knee Arthroplasty.

The oral Factor Xa inhibitor rivaroxaban (Xarelto) has been the pharmacologic agent used for venous thromboembolism (VTE) prophylaxis after primary hip and knee arthroplasty (THA/TKA) at our institution since February 2012. The purpose of our study was to compare rates of VTE and major bleeding between rivaroxaban and our previous protocol of enoxaparin after THA/TKA. A retrospective cohort study was performed including 2406 consecutive patients at our institution between 1/1/11 and 9/30/13. Patients who did not have unilateral primary THA/TKA or who received other anticoagulants were excluded. Of the 1762 patients included, 1113 patients (63.2%) received enoxaparin and 649 patients (36.8%) received rivaroxaban. This study found no demonstrable differences between these two anticoagulants in rates of VTE, infection, reoperation, transfusion, or major bleeding. Therapeutic, Retrospective comparative study, Level III.

Review of Canine Deaths While in Service in US Civilian Law Enforcement (2002-2012).

BACKGROUND: Working dogs have been proven effective in multiple military and law enforcement applications. Similar to their human counterparts, understanding mortality while still in service can help improve treatment of injuries, and improve equipment and training, to potentially reduce deaths. This is a retrospective study to characterize mortality of working dogs used in civilian law enforcement. METHODS: Reported causes of death were gathered from two working dog and law enforcement officer memorial websites. RESULTS: Of the 867 civilian law enforcement dogs reported to these memorial websites from 2002 to 2012 with reported causes of death while in service, the deaths of 318 were categorized as traumatic. The leading reported causes of traumatic death or euthanasia include trauma as a result of a vehicle strike, 25.8% (n=82); heatstroke, 24.8% (n=79); and penetrating ballistic trauma, 23.0% (n=73). CONCLUSION: Although the information gathered was from online sources, this study casts some light on the risks that civilian law enforcement dogs undergo as part of the tasks to which they are assigned. These data underscore the need for a comprehensive database for this specialized population of working dogs to provide the robust, reliable data needed to develop prevention and treatment strategies for this valuable resource.

Nanoscale structure of type I collagen fibrils: quantitative measurement of D-spacing.

This article details a quantitative method to measure the D-periodic spacing of type I collagen fibrils using atomic force microscopy coupled with analysis using a two-dimensional fast fourier transform approach. Instrument calibration, data sampling and data analysis are discussed and comparisons of the data to the complementary methods of electron microscopy and X-ray scattering are made. Examples of the application of this new approach to the analysis of type I collagen morphology in disease models of estrogen depletion and osteogenesis imperfecta (OI) are provided. We demonstrate that it is the D-spacing distribution, not the D-spacing mean, that showed statistically significant differences in estrogen depletion associated with early stage osteoporosis and OI. The ability to quantitatively characterize nanoscale morphological features of type I collagen fibrils will provide important structural information regarding type I collagen in many research areas, including tissue aging and disease, tissue engineering, and gene knockout studies. Furthermore, we also envision potential clinical applications including evaluation of tissue collagen integrity under the impact of diseases or drug treatments.

Type I collagen D-spacing in fibril bundles of dermis, tendon, and bone: bridging between nano- and micro-level tissue hierarchy.

Fibrillar collagens in connective tissues are organized into complex and diverse hierarchical networks. In dermis, bone, and tendon, one common phenomenon at the micrometer scale is the organization of fibrils into bundles. Previously, we have reported that collagen fibrils in these tissues exhibit a 10 nm width distribution of D-spacing values. This study expands the observation to a higher hierarchical level by examining fibril D-spacing distribution in relation to the bundle organization. We used atomic force microscopy imaging and two-dimensional fast Fourier transform analysis to investigate dermis, tendon, and bone tissues. We found that, in each tissue type, collagen fibril D-spacings within a single bundle were nearly identical and frequently differ by less than 1 nm. The full 10 nm range in D-spacing values arises from different values found in different bundles. The similarity in D-spacing was observed to persist for up to 40 µm in bundle length and width. A nested mixed model analysis of variance examining 107 bundles and 1710 fibrils from dermis, tendon, and bone indicated that fibril D-spacing differences arise primarily at the bundle level (∼76%), independent of species or tissue types.

Estrogen depletion results in nanoscale morphology changes in dermal collagen.

Tissue cryo-sectioning combined with atomic force microscopy imaging reveals that the nanoscale morphology of dermal collagen fibrils, quantified using the metric of D-periodic spacing, changes under the condition of estrogen depletion. Specifically, a new subpopulation of fibrils with D-spacings in the region between 56 and 59 nm is present 2 years following ovariectomy in ovine dermal samples. In addition, the overall width of the distribution, both values above and below the mean, was found to be increased. The change in width due to an increase in lower values of D-spacings was previously reported for ovine bone; however, this report demonstrates that the effect is also present in non-mineralized collagen fibrils. A nonparametric Kolmogorov-Smirnov test of the cumulative density function indicates a statistical difference in the sham and OVX D-spacing distributions (P<0.01).

Distribution of type I collagen morphologies in bone: relation to estrogen depletion.

Bone is an amazing material evolved by nature to elegantly balance structural and metabolic needs in the body. Bone health is an integral part of overall health, but our lack of understanding of the ultrastructure of healthy bone precludes us from knowing how disease may impact nanoscale properties in this biological material. Here, we show that quantitative assessments of a distribution of Type I collagen fibril morphologies can be made using atomic force microscopy (AFM). We demonstrate that normal bone contains a distribution of collagen fibril morphologies and that changes in this distribution can be directly related to disease state. Specifically, by monitoring changes in the collagen fibril distribution of sham-operated and estrogen-depleted sheep, we have shown the ability to detect estrogen-deficiency-induced changes in Type I collagen in bone. This discovery provides new insight into the ultrastructure of bone as a tissue and the role of material structure in bone disease. The observation offers the possibility of a much-needed in vitro procedure to complement the current methods used to diagnose osteoporosis and other bone disease.

Comparison of mean bone densities of three preparations of the distal portion of the equine third metacarpal bone measured by use of quantitative computed tomography.

OBJECTIVE: To evaluate whether cutting equine subchondral bone to demarcate specific regions of interest (ROIs) influences the mean density for that bone as measured via quantitative computed tomography (QCT). Sample population-2 metacarpophalangeal joints from equine cadavers. PROCEDURES: The distal portion of the third metacarpal bone of each intact metacarpophalangeal joint was scanned via CT to simulate in vivo conditions. Each joint was subsequently disarticulated and dissected, and the distal portion of the dissected third metacarpal bone in air was scanned. Then, six 1-cm(2) areas representing ROIs were cut into the distal condylar surfaces to depths of approximately 1 cm, and the bone was scanned again. Three-dimensional CT models of the 3 bone preparations were generated for each third metacarpal bone on the basis of data from each set of scan images, and densities of the 6 ROIs were measured. Mean bone densities for the 6 ROIs were compared among models of intact, dissected, and cut third metacarpal bone scans. RESULTS: Mean bone density was significantly lower in cut bone preparations, compared with that in intact or dissected bone. Differences between mean bone densities for intact and dissected bone preparations were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Cutting subchondral bone to demarcate specific ROIs prior to CT imaging significantly lowered mean bone density as measured via QCT and thus introduced substantial artifacts. These findings have direct implications on techniques for CT modeling of equine subchondral bone in the characterization of joint diseases in horses.

Reporter gene imaging using radiographic contrast from nonradioactive iodide sequestered by the sodium-iodide symporter.

The hypothesis that the human sodium-iodide symporter, NIS, can be used to detect NIS expression using standard radiological techniques was tested using adenoviral transduced NIS expression in human tumor xenografts grown in mice and in a naive dog prostate. Nonradioactive iodide was administered systemically to animals that 1-3 days previously had received a local injection of a replication-competent adenovirus expressing NIS under the control of the CMV promoter. The distribution of radiopacity was assessed in mouse tumors using micro-CT and a clinical X-ray machine and in the prostate of an anesthetized dog using a clinical spiral CT. Iodide sequestration and NIS expression were measured using X-ray spectrochemical analysis and fluorescence microscopy, respectively. Radiographic contrast due to NIS gene expression that was observed indicates the technique has potential for use in preclinical rodent tumor studies but probably lacks sensitivity for human use.

Comparison of gross and histopathologic findings with quantitative computed tomographic bone density in the distal third metacarpal bone of racehorses.

Comparison of subchondral bone density determined by quantitative computed tomography (CT) with gross and histopathologic changes have not been made in horses. The goal of this study was to determine if mean quantitative CT density and mean voxel standard deviation are associated with the presence and severity of osteochondral lesions in the palmar aspect of the distal third metacarpal bone in racing horses. Metacarpophalangeal joints from nine racehorses were imaged using CT and scored for gross damage. Four-millimeter-thick sagittal and 30 degrees palmar dorsal plane sections were cut, decalcified and stained with hematoxylin and eosin from the distal third metacarpal bone. Microscopic osteochondral lesions and subchondral remodeling were scored on a scale of 0-3. Percent subchondral bone, expressed as the ratio of bone volume to tissue volume, was also measured. Mean quantitative CT density and mean voxel standard deviation were measured from three-dimensional models of CT images comparable with histologic sections. Mean quantitative CT density was not associated with lesion severity or number of lesions. A weak correlation between mean quantitative CT density and gross score was found, but mean quantitative CT density was not predictive for gross score. Mean voxel standard deviation was not correlated with gross or histopathologic measures, but was predictive of mild osteochondral lesions. Results support the association of subchondral remodeling with the development of palmar metacarpal lesions. However, there was not a strong correlation between mean quantitative CT density or mean voxel standard deviation and histopathologic lesions of the distal third metacarpal bone.

Morphological changes in articular cartilage due to static compression: polarized light microscopy study.

We studied the deformation of the extracellular matrices in articular cartilage using a new compression-preservation method in histology. A Hoffman clamp was used to compress the tissue, which remained throughout the paraffin procedure and was removed from the embedded tissue block just before microtoming. Then 14 cartilage-bone blocks from 2 canine humeri were compressed for various strain levels from 5% to 65%. The histological sections were studied using a polarized light microscope, which generated a pair of two-dimensional maps of the fibril orientation (angle) and fibril organization (retardance) for each section. Results were 3-fold. One there was little change in the angle and retardance profiles of the tissue for strain levels 0-15% and a significant change in these profiles for strain levels 15% and above. Two for higher compression, more fibrils became aligned parallel to the articular surface; and three at approximately 30% strain, a second "transitional zone" was formed in the deep part of the tissue. We concluded that this novel compression procedure can be used effectively to study the altered architecture of the collagen matrix in compressed cartilage.

Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2.

The use of bone morphogenetic protein-2 (rhBMP-2) in spinal fusion has increased dramatically since an FDA approval for its use in anterior lumbar fusion with the LT cage. There are several reports of its use in transforaminal lumbar interbody fusion, posterolateral fusion, and anterior cervical fusion. Reports on adverse effects of rhBMP-2 when used in spinal fusion are scarce in literature. An Institutional Review Board approved retrospective study was conducted in patients undergoing anterior spinal fusion and instrumentation following diskectomy at a single center. Forty-six consecutive patients were included. Twenty-two patients treated with rhBMP-2 and PEEK cages were compared to 24 in whom allograft spacers and demineralized bone matrix was used. Patients filled out Cervical Oswestry Scores, VAS for arm pain, neck pain, and had radiographs preoperatively as well at every follow up visit. Radiographic examination following surgery revealed end plate resorption in all patients in whom rhBMP-2 was used. This was followed by a period of new bone formation commencing at 6 weeks. In contrast, allograft patients showed a progressive blurring of end plate-allograft junction. Dysphagia was a common complication and it was significantly more frequent and more severe in patients in whom rhBMP-2 was used. Post operative swelling anterior to the vertebral body on lateral cervical spine X-ray was significantly larger in the rhBMP-2 group when measured from 1 to 6 weeks after which it was similar. These effects are possibly due to an early inflammatory response to rhBMP-2 and were observed to be dose related. With the parameters we used, there was no significant difference in the clinical outcome of patients in the two groups at 2 years. The cost of implants in patients treated with rhBMP-2 and PEEK spacers was more than three times the cost of allograft spacers and demineralized bone matrix in 1, 2, and 3-level cases. Despite providing consistently good fusion rates, we have abandoned using rhBMP-2 and PEEK cages for anterior cervical fusion, due to the side effects, high cost, and the availability of a suitable alternative.

The effect of yield damage on the viscoelastic properties of cortical bone tissue as measured by dynamic mechanical analysis.

We have previously shown, using Dynamic Mechanical Analysis (DMA), that the presence of a defect in cortical bone tissue affects the apparent viscoelastic properties of that bone. However, mechanically induced damage is more complex than a machined defect making it difficult to predict its effect on bone viscoelasticity. We performed DMA measurements before and after introduction of yield damage into cortical bone beams from sheep radii. The specimens were placed in a DMA machine and baseline measurements of storage modulus (E1) and loss factor (tandelta) were performed using a 3-point bending configuration for a frequency range of 1-10 Hz. Measurements were done in all four bending directions (cranial, caudal, medial, and lateral) in random order. After subjecting the specimens to monotonic yield damage in a servohydraulic testing machine with the load applied to the cranial surface, oscillatory tests were repeated. To supplement results from the current experiment, additional analyses were performed on data from experiments where bone was either cut or fatigue-loaded between viscoelasticity measurements. Introduction of mechanical damage increased tan delta and frequency sensitivity of E1, consistent with the assertion that increased energy dissipation in damaged bone might contribute to its increased resistance to fatigue and fracture.

The mechanical phenotype of biglycan-deficient mice is bone- and gender-specific.

Biglycan (bgn) is a small leucine-rich proteoglycan (SLRP) enriched in the extracellular matrix of skeletal tissues. While bgn is known to be involved in the growth and differentiation of osteoblast precursor cells and regulation of collagen fibril formation, it is unclear how these functions impact bone's geometric and mechanical properties, properties which are integral to the structural function of bone. Because the genetic control of bone structure and function is both local- and gender-specific and because there is evidence of gender-specific effects associated with genetic deficiencies, it was hypothesized that the engineered deletion of the gene encoding bgn would result in a cortical bone mechanical phenotype that was bone- and gender-specific. In 11-week-old C57BL6/129 mice, the cortical bone in the mid-diaphyses of the femora and tibiae of both genders was examined. Phenotypic changes in bgn-deficient mice relative to wild type controls were assayed by four-point bending tests to determine mechanical properties at the whole bone (structural) and tissue levels, as well as analyses of bone geometry and bone formation using histomorphometry. Of the bones examined, bgn deficiency most strongly affected the male tibiae, where enhanced cross-sectional geometric properties and bone mineral density were accompanied by decreased tissue-level yield strength and pre-yield structural deformation and energy dissipation. Because pre-yield properties alone were impacted, this implies that the gene deletion causes important alterations in mineral and/or the matrix/mineral ultrastructure and suggests a new understanding of the functional role of bgn in regulating bone mineralization in vivo.