Radiological criteria for atypical features of femur fractures: what we can learn when applied in a clinical study setting.

The paper focuses on the identification of atypical fractures (AFFs). This paper examines the concordance between objective classification and expert subjective review. We believe the paper adds critical information about how to apply the American Society of Bone and Mineral Research (ASBMR) criteria to diagnose AFFs and is of high interest to the field. INTRODUCTION: Assess American Society of Bone and Mineral Research (ASBMR) criteria for identifying atypical femoral fractures (AFFs). METHODS: Two orthopedic surgeons independently evaluated radiographs of 372 fractures, applying ASBMR criteria. We assessed ease of applying ASBMR criteria and whether criteria-based assessment matched qualitative expert assessment. RESULTS: There was up to 27% uncertainty about how to classify specific features. 84% of films were classified similarly for the presence of AFF according to ASBMR criteria; agreement increased to 94% after consensus meeting. Of 37 fractures categorized as AFFs based on ASBMR criteria, 23 (62.2%) were considered AFFs according to expert assessment (not relying on criteria). Only one (0.5%) femoral shaft fracture that did not meet ASBMR criteria was considered an AFF per expert assessment. The number of major ASBMR features present (four vs five) and whether there was periosteal or endosteal thickening ("beaking" or "flaring") played major roles in the discrepancies between ASBMR criteria-based and expert-based determinations. CONCLUSIONS: ASBMR AFF criteria were useful for reviewers but several features were difficult to interpret. Expert assessments did not agree with the ASBMR classification in almost one-third of cases, but rarely identified an AFF when a femoral shaft fracture did not meet ASBMR AFF criteria. Experts identified lateral cortical transverse fracture line and associated new-bone formation along with no or minimal comminution as crucial features necessary for the definition of atypical femoral fractures.

Regulatory T cells: tolerance induction in solid organ transplantation.

The concept of regulatory T cell (Treg ) therapy in transplantation is now a reality. Significant advances in science and technology have enabled us to isolate human Tregs , expand them to clinically relevant numbers and infuse them into human transplant recipients. With several Phase I/II trials under way investigating Treg safety and efficacy it is now more crucial than ever to understand their complex biology. However, our journey is by no means complete; results from these trials will undoubtedly provoke both further knowledge and enquiry which, alongside evolving science, will continue to drive the optimization of Treg therapy in the pursuit of transplantation tolerance. In this review we will summarize current knowledge of Treg biology, explore novel technologies in the setting of Treg immunotherapy and address key prerequisites surrounding the clinical application of Tregs in transplantation.

Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation.

The validation of synthetic spectra used in the performance evaluation of radionuclide identifiers.

This work has evaluated synthetic gamma-ray spectra created by the RASE sampler using experimental data. The RASE sampler resamples experimental data to create large data libraries which are subsequently available for use in evaluation of radionuclide identification algorithms. A statistical evaluation of the synthetic energy bins has shown the variation to follow a Poisson distribution identical to experimental data. The minimum amount of statistics required in each base spectrum to ensure the subsequent use of the base spectrum in the generation of statistically robust synthetic data was determined. A requirement that the simulated acquisition time of the synthetic spectra was not more than 4% of the acquisition time of the base spectrum was also determined. Further validation of RASE was undertaken using two different radionuclide identification algorithms.

Harnessing stakeholder perspectives to improve the care of osteoporosis after a fracture.

UNLABELLED: This study used in-depth interviews and focus groups to evaluate osteoporosis care after a fracture. Patients (eligible women aged 67 who sustained a clinical fracture(s)), clinicians, and staff stated that an outreach program facilitated osteoporosis care management, but more-tailored education and support and increased participation of orthopedic specialists appear necessary. INTRODUCTION: Osteoporosis treatment reduces fracture risk, but screening and treatment are underutilized, even after a fracture has occurred. This study evaluated key stakeholder perspectives about the care of osteoporosis after a fracture. METHODS: Participants were from a nonprofit health maintenance organization in the United States: eligible women members aged 67 or older who sustained a clinical fracture(s) (n = 10), quality and other health care managers (n = 20), primary care providers (n = 9), and orthopedic clinicians and staff (n = 28); total n = 67. In-depth interviews and focus groups elicited participant perspectives on an outreach program to patients and clinicians and other facilitators and barriers to care. Interviews and focus group sessions were transcribed and content-analyzed. RESULTS: Patients, clinicians, and staff stated that outreach facilitated osteoporosis care management, but important patient barriers remained. Patient knowledge gaps and fatalism were common. Providers stated that management needed to begin earlier, and longer-term patient support was necessary to address adherence. Orthopedic clinicians and staff expressed lack of confidence in their osteoporosis management but willingness to encourage treatment. CONCLUSIONS: Although an outreach program assisted with the management of osteoporosis after a fracture, more-tailored education and support and increased participation of orthopedic specialists appear necessary to maximize osteoporosis management.

Total hip arthroplasty does not aid weight loss.

INTRODUCTION: Increased body mass index (BMI) is associated with the development of osteoarthritis of the hip. Many overweight patients with an arthritic hip cite restricted mobility and pain as impeding factors in their attempts to lose weight. There is an assumption that weight loss will occur after their surgery due to increased mobility. PATIENTS AND METHODS: The records of 180 patients who had undergone total hip arthroplasty (THA) were reviewed to identify BMI prior to, and 2 years after, surgery. RESULTS: BMI significantly increased postoperatively, both in patients with a pre-operative BMI in the recommended range (P < 0.001) and in those whose pre-operative BMI was indicative of obesity (P = 0.01). CONCLUSIONS: Irrespective of pre-operative BMI, reduction in body mass index did not occur following hip replacement surgery.

A benign psoas mass following metal-on-metal resurfacing of the hip.

As metal-on-metal arthroplasty becomes more widespread, concerns are being raised about the potential dangers of metal particulate debris. We present the case of a benign psoas mass secondary to the presence of such particles. The mass was excised and the hip resurfacing subsequently revised to a total hip replacement.

The accuracy of assessing total hip arthroplasty outcomes: a prospective correlation study of walking ability and 2 validated measurement devices.

The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the SF-36 are used to assess subjective outcome after total hip arthroplasty (THA). Although these indices have been validated, neither the WOMAC nor the SF-36 has been tested for accuracy against objective data in this clinical setting. Thirty osteoarthritic patients undergoing elective primary THA were subjectively evaluated preoperatively and 1 year postoperatively with the WOMAC and the SF-36 and objectively evaluated at the same interval with basic stride analysis and the 6-minute walk test. Correlation analysis of the subjective and objective data (both perioperative improvement and postoperative absolute scores) yielded Pearson coefficients of r = 0.50-0.81. This work demonstrates a sound statistical relationship between walking ability and the functional aspects of the WOMAC and the SF-36, supporting the use of these instruments in assessing the functional outcome after THA.

Finding patients after 40 years: a very long term follow-up study of the Colonna arthroplasty.

Between 1952 and 1965, surgeons at the Los Angeles Shriners Hospital managed 23 hips with the Colonna two-stage capsular arthroplasty, a procedure originally described in 1936 with very stringent indications for the treatment of childhood hip dysplasia. By using chart review, credit traces, telephone listings software, and the Internet, we found 17 (90%) of 19 patients known to be alive 40 years after surgery. Only four of 16 patients questioned have not undergone total hip arthroplasty, and these patients were no better candidates for the Colonna arthroplasty than were the 12 patients who have required hip-replacement surgery. We do not support revival of this now obscure procedure. However, we do attest that the average clinical investigator currently has access to tools that allow reliable location of patients for very long term follow-up. This technology will improve the accuracy and statistical power of outcomes research.

Impact of declining reimbursement and rising hospital costs on the feasibility of total hip arthroplasty.

Total hip arthroplasty, although a very successful clinical treatment, remains an expensive procedure in an era of constrained health care resources. Hospitalization cost, charge, and reimbursement data were compared between all patients who underwent elective, primary, unilateral total hip arthroplasty in 1988 and 1993 at the UCLA Medical Center. Although length of hospitalization decreased by 36%, increases both in unit supply costs and in the intensity of hospital services prevented a statistically significant reduction in total hospitalization cost. Reimbursement declined by 27% after calculating inflation with the Consumer Price Index for Medical Care. Further, the margin by which reimbursement exceeded cost decreased from 66% in 1988 to 8% in 1993. These trends constitute a serious threat to the financial feasibility of total hip arthroplasty.

Contribution of the anterolateral joint capsule to the mechanical stability of the ankle.

Published reports describe the clinical efficacy of modified Brostrom anatomic repairs, surgical procedures that involve repair and fortification of the lateral capsuloligamentous complex of the ankle for patients suffering from chronic lateral instability of this joint. A cadaveric serial sectioning study of the anterior talofibular ligament, the calcaneofibular ligament, and the remainder of the anterolateral joint capsule was completed to quantitate the contribution of the superior portion of the anterolateral joint capsule, independent of the other two structures, to the overall mechanical stability of the lateral ankle. Using 20 fresh frozen specimens, talar tilt and anterior drawer stress radiographs were taken before and after sectioning these anatomic structures in an order established by one of two protocols. Sectioning of the superior anterolateral joint capsule caused 17% to 18% of the total displacement in a Grade II sprain simulation and 29% to 33% of the total displacement in a Grade III sprain simulation. This work suggests that disruption of the segment of ankle joint capsule superior to the anterior talofibular ligament creates approximately 30% of the overall laxity encountered in a Grade III inversion sprain, substantiating the principle of restoring the integrity of the entire anterolateral joint capsule when operating on a chronically unstable ankle.

Strength of fixation with transosseous sutures in rotator cuff repair.

The effect of various configurations of placement of transosseous sutures on the immediate strength of fixation was studied in forty-five fresh-frozen humeri from cadavera of older individuals (mean age at the time of death, sixty-three years). The ultimate strength (the strength to failure) was significantly greater (p < 0.05) when the sutures were placed at sites more distal to the tip of the greater tuberosity or when the sutures were tied over a wider bone bridge. Cortical augmentation with use of a plastic button through which the transosseous sutures were tied increased the ultimate strength approximately 1.9-fold. The increase in the ultimate strength of the transosseous repair corresponded significantly with the increasing mean thickness of the cortical bone as the sutures were placed more distally along the lateral aspect of the humerus. We concluded that the strength of the fixation of a rotator cuff repair can be increased by placing the transosseous sutures at least ten millimeters distal to the tip of the greater tuberosity and by tying them over a bone bridge that is at least ten millimeters wide. When bone is very osteoporotic, cortical augmentation with a readily available plastic button strengthens the repair.

Stride analysis after proximal tibial replacement.

Ten patients who had undergone primary intraarticular proximal tibial replacement between April 1985 and December 1994, and had a minimum of 2 years of followup, were available for stride analysis. Mean age, time since intraarticular proximal tibial replacement, height, and weight were 23.8 years, 6.5 years, 167 cm, and 63 kg, respectively. A volunteer control group of five male patients who had undergone above knee amputation was obtained from the local community. The mean age, time since above knee amputation, height, and weight were 43.6 years, 24.1 years, 165 cm, and 70 kg, respectively. Stride analysis was performed over the central 6-m portion of a 10-m walkway at a self selected, comfortable pace. Gait velocity, stride length, cadence, and stance time symmetry were measured. Velocity after intraarticular proximal tibial replacement versus above knee amputation was 79.2 +/- 7.6 m per minute versus 71.4 +/- 5.4 m per minute. Cadence after intraarticular proximal tibial replacement versus above knee amputation was 112.4 +/- 10.6 steps per minute versus 110.1 +/- 2.4 steps per minute. There were no significant differences between stride length (1.41 +/- 0.13 m versus 1.43 +/- 0.12 m) and stance time symmetry (0.90 +/- 0.07 versus 0.87 +/- 0.11) for intraarticular proximal tibial replacement versus above knee amputation. The results suggest that endoprosthetic reconstruction resulted in a gait comparable with that after above knee amputation with an external prosthesis.

The effects of collagen fiber orientation, porosity, density, and mineralization on bovine cortical bone bending properties.

The relationship between the mechanical properties of bone in three-point bending and eight histocompositional variables was studied. Ultimate stress, ultimate strain, and elastic modulus were measured in 35 beams of cortical bone from bovine tibias using standard ASTM methods. Four elements of porosity were determined by point counting, mineralization by ashing, and wet and dry apparent density from weight and volume. Collagen fiber orientation was estimated using polarized light, and specimens were categorized as plexiform, mixed, or osteonal. Analysis of variance showed that ultimate stress was similar in the plexiform and osteonal specimens, but elastic modulus was reduced in the latter (18.6 +/- 1.2 vs 21.0 +/- 1.9 GPa), which were significantly less porous (by 24%) and less mineralized (by 3%) than the plexiform group. Stepwise multiple regression analysis showed that collagen fiber orientation ranked highly as a predictor of bending properties. The next best predictors were density and mineralization. In the plexiform group, 77% of the variability in elastic modulus was accounted for by wet and dry density and collagen fiber orientation. In the osteonal group, 88% of modulus variability was accounted for by percentage mineralization and collagen fiber orientation. When all the specimens were pooled, 62% of the variability in elastic modulus was attributable to variations in collagen fiber orientation, density, and porosity due to Haversian canals.

Three-dimensional flow in the upper ocean.

Measurements made from the Research Platform FLIP provide some of the first direct observations of three-dimensional flow within the surface mixed layer of the ocean. Relatively narrow regions of downwelling flow were found within the mixed layer, in coincidence with bands of convergent surface flow. At mid-depth in the mixed layer, the downwelling flow had magnitudes of up to 0.2 meter per second and was accompanied by a downwind, horizontal jet of comparable magnitude. There is some evidence that these motions transport heat and phytoplankton within the mixed layer.