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].

Use of MicroRNA biomarkers to distinguish enchondroma from low-grade chondrosarcoma.

Establishing a definitive diagnosis between benign enchondroma versus low-grade chondrosarcoma presents a potential challenge to both clinicians and pathologists. microRNAs (small non-coding RNAs) have proven to be effective biomarkers for the identification of tumors and tumor progression. We present analysis, both array and quantitative PCR, that shows consistently and substantially increased expression of two microRNAs, miRs-181a and -138, in low-grade chondrosarcomas compared with enchondromas. The data suggest these microRNAs would provide an analytical distinction between the chondrosarcoma and benign neoplasms that can be performed in formalin-fixed paraffin-embedded specimens. Together with recent publications, these data indicate that miRs-181a and -138 also play a role in tumor development and homeostasis and may provide new targets for the development of much needed therapeutic intervention.

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.].

Meniscus Induced Cartilaginous Damage and Non-linear Gross Anatomical Progression of Early-stage Osteoarthritis in a Canine Model.

BACKGROUND: The predictable outcome of the anterior cruciate ligament transection (ACLT) canine model, and the similarity to naturally occurring osteoarthritis (OA) in humans, provide a translatable method for studying OA. Still, evidence of direct meniscus-induced cartilaginous damage has not been identified, and gross-anatomical blinded scoring of early-stage OA has not been performed. OBJECTIVE: A gross anatomical observation and statistical analysis of OA progression to determine meniscus induced cartilaginous damage, to measure the macroscopic progression of OA, and to address matters involving arthroscopic and surgical procedures of the knee. METHOD: Unblinded assessment and blinded scoring of meniscal, tibial, femoral, and patellar damage were performed for control and at four time points following unilateral ACLT: 3-week (N=4), 8-week (N=4), 12-week (N=5), and 25-week (N=4). Mixed-model statistics illustrates damage (score) progression; Wilcoxon rank-sum tests compared time-point scores; and Wilcoxon signed-rank tests compared ACLT and contralateral scores, and meniscus and tibia scores. RESULT: Damage was manifest first on the posterior aspect of the medial meniscus and subsequently on the tibia and femur, implying meniscal damage can precede, coincide with, and aggravate cartilage damage. Damage extent varied chronologically and was dependent upon the joint component. Meniscal damage was evident at 3 weeks and progressed through 25-weeks. Meniscal loose bodies corresponded to tibial cartilage damage location and extent through 12 weeks, followed by cartilage repair activity after complete meniscal degeneration. CONCLUSION: This study provides additional information for understanding OA progression, identifying OA biomarkers, and arthroscopic and meniscectomy procedures.

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.

Effects of cryopreservation on the depth-dependent elastic modulus in articular cartilage and implications for osteochondral grafting.

Cryopreservation of articular cartilage is often used in storage of experimental samples and osteochondral grafts, but the depth-dependence and concentration of glycosaminoglycan (GAG) are significantly altered when cryogenically stored without a cryoprotectant, which will reduce cartilage stiffness and affect osteochondral graft function and long-term viability. This study investigates our ability to detect changes due to cryopreservation in the depth-dependent elastic modulus of osteochondral samples. Using a direct-visualization method requiring minimal histological alterations, unconfined stepwise stress relaxation tests were performed on four fresh (never frozen) and three cryopreserved (-20 °C) canine humeral head osteochondral slices 125 ± 5 µm thick. Applied force was measured and tissue images were taken at the end of each relaxation phase using a 4× objective. Intratissue displacements were calculated by tracking chondrocytes through consecutive images for various intratissue depths. The depth-dependent elastic modulus was compared between fresh and cryopreserved tissue for same-depth ranges using analysis of variance (ANOVA) with Tukey post-test with a 95% confidence interval. Cryopreservation was found to significantly alter the force-displacement profile and reduce the depth-dependent modulus of articular cartilage. Excessive collagen fiber folding occurred at 40-60% relative depth, producing a "black line" in cryopreserved tissue. Force-displacement curves exhibited elongated toe-region in cryopreserved tissue while fresh tissue had nonmeasurable toe-region. Statistical analysis showed significant reduction in the elastic modulus and GAG concentration throughout the tissue between same-depth ranges. This method of cryopreservation significantly reduces the depth-dependent modulus of canine humeral osteochondral samples.

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.

Technical note: a histological technique for detecting the cryptic preservation of erythrocytes and soft tissue in ancient human skeletonized remains.

Bone samples from a Middle Bronze Age (ca., 1600-1300 BC) site were prepared for histological analysis. Preliminary results suggested that components of bone marrow remained preserved. To verify these findings and optimize the sample preparation procedure, we conducted experiments varying the type of acid used to decalcify the bones for histology preparation, as well as the exposure time to the demineralizing agents and thickness of sections taken from the samples for slide preparation. Subsequent examination of the slides revealed the presence of well-preserved erythrocytes and other cellular structures consistent with bone marrow. Our results demonstrate that the traditional methods used to prepare bone samples for histology may be adjusted to improve the quality of the soft tissue architecture and cellular morphology for histological observation.

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).

Patterns of mouthguard utilization among atom and pee wee minor ice hockey players: a pilot study.

OBJECTIVE: To determine if youth hockey players wear their mouthguards properly, and if not, why? DESIGN: Descriptive cross-sectional study. SETTING: Tecumseh Shoreline Minor Hockey Association, Tecumseh, Ontario, Canada, during the 2007-2008 season. PARTICIPANTS: Subjects were 180 travel hockey players of the Tecumseh Shoreline Minor Hockey Association at the Atom or Pee Wee level (aged 9-12 y) or their competitors. ASSESSMENT OF RISK FACTORS: Players were asked to complete a survey addressing mouthguard wear under their coach's supervision. MAIN OUTCOME MEASURES: The type of mouthguard, whether mouthguards were worn at all and worn properly, and the reasons for noncompliance. The incidence of concussion and association to mouthguard-wearing tendencies were also assessed. RESULTS: Sixty-eight percent [95% confidence interval (CI), 60.4%-74.5%] of subjects always wore their mouthguards, but only 31.7% (95% CI, 25.0%-39.0%) wore them properly during games and 51.1% (95% CI, 43.6%-58.6%) during practice. Custom-made mouthguards were most likely to be worn properly, followed by boil-and-bite and stock-type guards. Younger players wore mouthguards more consistently than older players (P < 0.01). Reasons for not wearing the guard included the following: 43.0% (95% CI, 35.4%-50.4%) of subjects felt it made talking difficult, 27.4% (95% CI, 20.9%-34.3%) felt it uncomfortable, 23.9% (95% CI, 17.9%-30.8%) felt it made breathing difficult, and 12.4% (95% CI, 8.3%-17.9%) thought it did not fit correctly. The incidence of concussion was 17.8%, but the study was underpowered for any association with mouthguard type. CONCLUSIONS: Even when mouthguards are mandated to be worn in a children's travel hockey league, young players self-report that they routinely fail to wear them properly.

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.

Hip dislocation after modular unipolar hemiarthroplasty.

An institutional review board-approved retrospective review of hip fractures in elderly patients treated with a modular unipolar implant was carried out to identify factors predisposing to dislocation of a hemiarthroplasty. The main outcome measure evaluated was dislocation vs nondislocation. Two hundred seventeen patients underwent the surgery, and 174 were available for review at 6 weeks and 144 at 1 year. The incidence of dislocation was 6%. The average time of dislocation after surgery was 19.3 days. Clinical factors significant for dislocation were male sex and mental disease. Radiographic factors in dislocated hips included a smaller femoral neck and contralateral femoral neck offset. The center edge angle was also smaller in the dislocated patients. These patients had a higher mortality rate.

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.