Evaluation of Bone Formation on Orthopedic Implant Surfaces Using an Ex-Vivo Bone Bioreactor System

Recent advances in materials and manufacturing processes have allowed the fabrication of intricate implant surfaces to facilitate bony attachment. However, refinement and evaluation of these new design strategies are hindered by the cost and complications of animal studies, particularly during early iterations in the development process. To address this problem, we have previously constructed and validated an ex-vivo bone bioreactor culture system that can maintain the viability of bone samples for an extended period ex-vivo. In this study, we investigated the mineralization of a titanium wire mesh scaffold under both static and dynamic culturing using our ex vivo bioreactor system. Thirty-six cancellous bone cores were harvested from bovine metatarsals at the time of slaughter and divided into five groups under the following conditions: Group 1) Isolated bone cores placed in static culture, Group 2) Unloaded bone cores placed in static culture in contact with a fiber-mesh metallic scaffold, Group 3) Bone cores placed in contact with a fiber-mesh metallic scaffold under the constant pressure of 150 kPa, Group 4) Bone core placed in contact with a fiber-mesh metallic scaffold and exposed to cyclic loading with continuous perfusion flow of media within the ex-vivo culture system and Group 5) Bone core evaluated on Day 0 to serve as a positive control for comparison with all other groups at weeks 4 and 7. Bone samples within Groups 1-4 were incubated for 4 and 7 weeks and then evaluated using histological examination (H&E) and the Live-Dead assay (Life Technologies). Matrix deposits on the metallic scaffolds were examined with scanning electron microscopy (SEM), while the chemical composition of the matrix was measured using energy-dispersive x-ray spectroscopy (EDX). We found that the viability of bone cores was maintained after seven weeks of loading in our ex vivo system. In addition, SEM images revealed crystallite-like structures on the dynamically loaded metal coupons (Group 4), corresponding to the initial stages of mineralization. EDX results further confirmed the presence of carbon at the interface and calcium phosphates in the matrix. We conclude that a bone bioreactor can be used as an alternate tool for in-vivo bone ingrowth studies of new implant surfaces or coatings

Level of Pain and Disability at Time of TKR across the Past 10 Years: Results from Two National Cohorts

Introduction: A recent analysis reported a growing numbers of younger US adults with knee pain consistent with osteoarthritis (OA), although parallel analyses of knee x-rays found no increase in the classic radiographic signs of OA. The accompanying editorial evoked the need to understand if surgeons are performing surgery at an earlier stage in the condition.1 We compared pre-operative demographic and symptom profiles of a national US cohort of OA patients undergoing primary total knee replacement (TKR) in 2011-2012 with a national US cohort of patients from 2000-2004 to evaluate change, if any, in the timing of surgery as measured by patient pain and function. Methods: Following informed consent, the 2011-2012 national research study collected comprehensive data including demographic, comorbidity, and patient-reported pain and physical function, from a national sample of TKR patients. Comparable data from a national sample collected by one implant manufacturer between 2000-2004 were analyzed. Descriptive statistics compared the demographic and symptom profiles of the two cohorts. Results: There were fewer females in the 2011-2012 cohort (n=2363) compared to the 2000-2004 cohort (n=7144) (61.62%, vs. 66.72%). The 2011-2012 cohort was younger than the 2000-2004 cohort (66.7 years, vs. 68.12 years) and had a lower mean BMI (31.5 vs 32.3). Pre-operative physical function scores (SF36/PCS) were 3 points higher in 2011-2012 than 2000-2004 (33.2 vs. 30.41). When compared to the national PCS norm of 50 (SD=10), TKR patients from both time periods reported pre-operative function levels almost 2 standard deviations below the national norm. There was no significant difference in terms of emotional health (SF36/MCS scores: 51.85 for the 2011-2012 cohort vs. 51.83 for the 2000-2004 cohort). Conclusion: Despite the significant growth in the use of primary TKR in the last decade, especially among younger patients, TKR patients continue to report significant disability at the time of surgery

Differential Burden of Musculoskeletal Pain in Blacks and Whites at the Time of Total Joint Replacement Surgery

Introduction: The existence of racial disparities in total knee (TKR) and hip (THR) replacement outcomes is well established. The role of musculoskeletal co-morbidities among black and white TKR patients at the time of surgery were investigated in a prospective cohort enrolled in the FORCE-TJR consortium of 131 surgeons in 22 US states. Materials & methods: Descriptive analyses were performed on 3,306 TKR and 2,439 THR patients. Data included sociodemographic factors (age, sex, race), BMI, comorbid conditions using the modified Charlson comorbidity scores, burden of musculoskeletal disease using the Knee/Hip injury and Osteoarthritis Outcome Score (KOOS/HOOS) in both knees and hips, emotional health based on the Short Form 36 (SF-36) Mental Component Score (MCS) and physical function based on the Physical Component Score (SF-36 PCS). Factors associated with pre-operative surgical joint pain and function were examined using multivariate stepwise linear regression models. Results: Compared to Whites, Blacks (143 hips and 201 knees) reported worse surgical joint pain (mean pain: 39.3 vs. 49.2 (hip); 43.4 vs. 53.2 (knee)), poorer surgical joint function (mean function: 38.9 vs. 45.7 (hip); 45.9 vs. 53.4 (knee)), poorer global function (mean PCS: 30.0 vs. 31.6 (hip); 31.3 vs. 33.1 (knee)), and more non-operative joints pain. (All p\u3c0.03). In adjusted multivariable models, differences at the time of surgery in surgical joint symptoms and global function were explained by differences in musculoskeletal pain in the hips, knees, and low back. Conclusion: Greater burden of musculoskeletal pain explains differences in pre-operative pain and function between Blacks and Whites and likely impacts rehabilitation and subsequent TJR outcomes

Differential burden of musculoskeletal pain in African Americans and whites patients at the time of total joint replacement surgery

Objective: African Americans patients have greater operative joint pain and functional limitation at the time of total joint replacement (TJR) compared to white patients. We examined the factors associated with this apparent disparity. Methods: A consecutive sample of 5745 patients with advanced knee and hip osteoarthritis [who elected to undergo TJR in 2011-201] reported, preoperatively, medical comorbidities, operative and non-operative hip/ knee pain using Hip and Knee Disability and Osteoarthritis Outcome Scores (HOOS/KOOS), function using Short Form 36 Physical Component Score (PCS). Total burden of musculoskeletal pain was quantified as moderate/severe pain in non-operative hip and knee joints and lumbar back pain using Oswestry Disability Index (ODI). Associations among race, medical co-morbidites (modified Charlson), total musculoskeletal pain burden, operative joint pain, and functional limitations were examined using multivariable regression models. Results:Compared to Whites, African Americans (143 hips and 201 knees) reported worse surgical joint pain (mean pain: 39.3 vs. 49.2 [hip]; 43.4 vs. 53.2 [knee]), poorer surgical joint function (mean function: 38.9 vs. 45.7 [hip]; 45.9 vs. 53.4 [knee]), poorer global function (mean PCS: 30.0 vs. 31.6 [hip]; 31.3 vs. 33.1 [knee]), and more non-operative joints pain (p Conclusions: Greater burden of musculoskeletal pain explains differences in pre-operative pain and function between African American and white patients and likely impacts rehabilitation and subsequent TJR outcomes

Millennial scale control of European climate by the North Atlantic Oscillation from 12,500 BP: the Asiul speleothem record

Contemporary climate in Europe is strongly influenced by the North Atlantic Oscillation (NAO), the atmospheric pressure dipole between Iceland and the Azores1. Under positive NAO conditions winter storm tracks associated with the Atlantic Westerly Jet (AWJ) migrate northwards, leading to wetter and warmer winter conditions in north-western Europe and dry conditions in southern Europe; including the Iberian Peninsula. Under the negative NAO phase, storm tracks weaken and shift southwards reversing the pattern1. Existing proxy records of the NAO suggest that this atmospheric process only began to dominate European climate at approximately 8000 years BP, related to the final breakup of the Laurentide ice shelf2. However, here we present evidence of precipitation changes from a high-resolution speleothem δ18O record from northern Iberia, which indicates NAO-like forcing extending throughout the Holocene and into the Younger Dryas (YD) at 12,500 years BP. These variations in precipitation delivery relate to an underlying millennial scale cycle in NAO dynamics. The speleothem δ18O is strongly correlated to existing records of North Atlantic Ocean ice rafted debris (IRD)3, indicating an NAO-like connection with oceanic circulation during the Holocene2. These large-scale atmospheric processes have dramatically influenced the delivery of precipitation to northern Iberia and may have played a decisive role in environmental and human development in the region, throughout the Holocene

North Atlantic forcing of moisture delivery to Europe throughout the Holocene

Century-to-millennial scale fluctuations in precipitation and temperature are an established feature of European Holocene climates. Changes in moisture delivery are driven by complex interactions between ocean moisture sources and atmospheric circulation modes, making it difficult to resolve the drivers behind millennial scale variability in European precipitation. Here, we present two overlapping decadal resolution speleothem oxygen isotope (δ18O) records from a cave on the Atlantic coastline of northern Iberia, covering the period 12.1–0 ka. Speleothem δ18O reveals nine quasi-cyclical events of relatively wet-to-dry climatic conditions during the Holocene. Dynamic Harmonic Regression modelling indicates that changes in precipitation occurred with a ~1500 year frequency during the late Holocene and at a shorter length during the early Holocene. The timing of these cycles coincides with changes in North Atlantic Ocean conditions, indicating a connectivity between ocean conditions and Holocene moisture delivery. Early Holocene climate is potentially dominated by freshwater outburst events, whilst ~1500 year cycles in the late Holocene are more likely driven by changes internal to the ocean system. This is the first continental record of its type that clearly demonstrates millennial scale connectivity between the pulse of the ocean and precipitation over Europe through the entirety of the Holocene

U-Pb geochronology and global context of the Charnian Supergroup, UK: constraints on the age of key Ediacaran fossil assemblages

U-Pb (zircon) ages for key stratigraphic volcanic horizons within the ∼3200-m-thick Ediacaran-age Charnian Supergroup provide an improved age model for the included Avalonian assemblage macrofossils and, hence, temporal constraints essential for intercomparisons of the Charnian fossils with other Ediacaran fossil assemblages globally. The Ives Head Formation (Blackbrook Group), the oldest exposed part of the volcaniclastic Charnian Supergroup of the late Neoproterozoic Avalonian volcanic arc system of southern Britain, contains a bedding plane with an impoverished assemblage of ivesheadiomorphs that is constrained to between ca. 611 Ma and 569.1 ± 0.9 Ma (total uncertainty). Higher-diversity biotas, including the holotypes of Charnia, Charniodiscus, and Bradgatia, occupy the upper part of the volcaniclastic succession (Maplewell Group) and are dated at 561.9 ± 0.9 Ma (total uncertainty) and younger by zircons interpreted as coeval with eruption and deposition of the Park Breccia, Bradgate Formation. An ashy volcanic-pebble conglomerate in the Hanging Rocks Formation at the very top of the supergroup yielded two U-Pb zircon populations: an older detrital one at ca. 604 Ma, and a younger population at ca. 557 Ma, which is interpreted as the approximate depositional age. The temporal association of the fossiliferous Charnian Supergroup with comparable fossiliferous deep-water successions in Newfoundland, and the probable temporal overlap of the youngest Charnwood macrofossils with those from different paleoenvironmental settings, such as the Ediacaran White Sea macrofossils, indicate a primary role for ecological sensitivity in determining the composition of these late Neoproterozoic communities

Greater Co-morbidity Burden is Associated with Greater Pain and Disability at Time of Total Knee Replacement Among African American Patients

Introduction: The existence of racial disparities in total joint replacement (TJR) care is well established based on Medicare and VA data.1,3 As compared to white patients, African American TJR patients have lower utilization rates, more pain, poorer function at the time of surgery, and higher post-operative complication rates.2,3 We analyzed a national prospective total knee replacement (TKR) cohort to further investigate patterns of medical and musculoskeletal co-morbidities among African American and white TKR patients. Methods: Descriptive analyses were performed on a national database (FORCE-TJR) of 3,313 TKR patients from 107 orthopedic surgeons. Data collected include patient sociodemographics (age, gender, race, education, insurance, household income, smoking status), modified Charlson co-morbidity scores, and pre-operative and post-operative pain and function scores (SF-36 PCS and MCS, WOMAC, KOOS/HOOS ADL score). To assess the total musculoskeletal pain burden, WOMAC pain scores were recorded for non-operative weight bearing joints as well as Oswestry low back pain scores. Multivariate models are in progress. Results: Preliminary descriptive analyses demonstrate a higher medical co-morbidity burden in African American TKR patients as compared to whites (COPD, DM, smoking), as well as worse baseline pain (mean WOMAC pain score = 43.46 vs. 52.92, p Conclusion: Preliminary results demonstrate significant differences in medical and musculoskeletal co-morbidities that correlate with poorer pain and function scores in African American patients at the time of TKR

Location of All-cause 30-day Readmission Following Total Joint Replacement: Surgical Hospital Versus Outside Hospital

Background: Evaluating posthospital complications and hospital readmissions in the United States is limited under the current system. This is due to an inability to quantify posthospital care delivered to patients at locations other than the surgical hospital. In order to circumvent this issue, information can be sought directly from patients about posthospital health care utilization. This approach provides a more complete record in comparison with methods that evaluate complications treated only at the surgical hospital. Methods: Participants undergoing total joint replacement (TJR) between 5/10/11 and 5/17/11 were identified from the Function and Outcomes Research in Comparative Effectiveness Registry (FORCE-TJR) cohort. The cohort is a nationally representative sample of TJR patients undergoing total knee replacement and total hip replacement. Patients are asked to self-report complications on the six-month follow-up questionnaire. The questionnaire specifically inquires about any emergency department visit, outpatient surgery, or hospital admission that occurred within six months of the total joint replacement surgery. For each positive report of postoperative complication, the pertinent medical records are retrieved and reviewed and discharge diagnoses are used to identify whether the complication is a surgical site symptom or a medical complication. The location of the care is identified as the surgical hospital or an outside hospital. We report on the location of all readmissions within 30 days of discharge from the initial TJR surgery. Results: In total, our sample yielded 112 validated patient-reported readmissions following TJR. Of these readmissions, 75% were treated at the surgical hospital and 25% were treated at an outside hospital. Patients receiving care at the surgical hospital were similar in terms of demographics compared with those seeking care at an outside hospital in terms of mean age (66.7 years vs. 66.9 years, p=0.92), and gender (67.9% male vs. 63.1% male, p=0.65). Additionally, the mean number of days since discharge was similar (16.7 days vs. 15.1 days, p = 0.45) among patients treated at the surgical hospital compared with those treated at an outside hospital. Discharge diagnoses varied by the location of care. At the surgical hospital, discharge diagnoses identified surgical site symptoms as the cause of 36.9% of admissions and medical conditions as the cause of 63.1% of admissions. When compared with discharge diagnoses at outside hospitals, surgical site symptoms accounted for 17.9% of admissions and medical conditions for 82.1% (p=0.067). Conclusion: Public reporting of all post-TJR discharge complications is currently used to compare quality of care between hospitals. However, our study demonstrates that hospitals and surgeons may underestimate their complication rates by 25%. This suggests that novel approaches, such as direct to patient contact, are needed to minimize missing post-hospital event data

Development of a Personalized Shared Decision-Making Tool for Knee Osteoarthritis and User-Testing With African American and Latina Women

BACKGROUND: Patients with chronic knee pain are often unaware of treatment options and likely outcomes-information that is critical to decision-making. A consistent framework for communicating patient-personalized information enables clinicians to provide consistent, targeted, and relevant information. Our objective was to user-test a shared decision-making (SDM) tool for chronic knee pain. METHODS: A cross-functional team developed a Markov-based health economics model and tested the model outputs with patient panels, patient and clinician focus groups, and clinical specialists. The resulting SDM tool was user-tested in a parallel-designed, randomized controlled study with 52 African American and 52 Latina women from geographically representative areas of the US. Participants were randomized to counseling with or without the SDM tool. Feedback was collected at intervention and at 1 month after intervention and analyzed with Student\u27s t-tests and Chi-squared analyses (alpha = 0.05). RESULTS: Qualitative results indicated patients understood the material, rated the overall experience highly, and were likely to recommend the physician. The SDM group reported high satisfaction with the tool. A greater proportion of the SDM group (56%) reported increased physical activity over baseline at 1 month compared with the control group (33%) ( CONCLUSION: Use of this innovative SDM tool was associated with high satisfaction and a significant increase in self-reported physical activity level at 1 month. The SDM tool may elicit behavioral changes to promote musculoskeletal health