Clinical and Computational Evaluation of an Anatomic Patellar Component.

BACKGROUND: Anatomic patellar components for total knee arthroplasty (TKA) have demonstrated favorable in vivo kinematics. A novel failure mechanism in TKA patients with an anatomic patellar component was observed prompting an investigation to identify patient- and implant-related factors associated with suboptimal performance. METHODS: A retrospective evaluation was performed comparing 100 TKA patients with an anatomic patellar component to 100 gender-, age-, and body mass index-matched patients with a medialized dome component. All surgeries were performed with the same posterior-stabilized TKA system with minimum of 1-year follow-up. Several radiographic parameters were assessed. A separate computational evaluation was performed using finite-element analysis, comparing bone strain energy density through the patella bone remnant. RESULTS: Patients with an anatomic patellar component had significantly higher rates of anterior knee pain (18 versus 2%, P < .001), chronic effusions (18 versus 2%, P < .001), and superior patellar pole fragmentation (36 versus 13%, P < .001) compared to those with a dome component. Radiographically, the anatomic group demonstrated more lateral patellar subluxation (2.3 versus 1.1 mm, P < .001) and lateral tilt (5.4 versus 4.0 mm, P = .013). Furthermore, there were more revisions in the anatomic group (7 versus 3, P = .331). On computational evaluation, all simulations demonstrated increased bone strain energy density at the superior patellar pole with the anatomic patella. Resection thickness <13 mm resulted in over 2-fold higher strain energy density, and negative resection angle of 7° resulted in 6-fold higher superior pole strain energy. CONCLUSIONS: Patients with an anatomic patellar component showed higher rates of anterior knee pain, chronic effusion, and superior pole fragmentation compared to patients with a dome patella, with higher superior patellar pole strain energy confirmed on computational evaluation. Avoiding higher resection angles and excessive patellar resection may improve the performance and survivorship of the anatomic patella.

Phase Stability of Hexagonal/Cubic Boron Nitride Nanocomposites.

Boron nitride (BN) is an exceptional material, and among its polymorphs, two-dimensional (2D) hexagonal and three-dimensional (3D) cubic BN (h-BN and c-BN) phases are most common. The phase stability regimes of these BN phases are still under debate, and phase transformations of h-BN/c-BN remain a topic of interest. Here, we investigate the phase stability of 2D/3D h-BN/c-BN nanocomposites and show that the coexistence of two phases can lead to strong nonlinear optical properties and low thermal conductivity at room temperature. Furthermore, spark-plasma sintering of the nanocomposite shows complete phase transformation to 2D h-BN with improved crystalline quality, where 3D c-BN possibly governs the nucleation and growth kinetics. Our demonstration might be insightful in phase engineering of BN polymorph-based nanocomposites with desirable properties for optoelectronics and thermal energy management applications.

Component Rotation in Well-Functioning, Gap Balanced Total Knee Arthroplasty Without Navigation.

BACKGROUND: Malalignment of total knee arthroplasty (TKA) components is a potential cause of clinical failure following TKA. Since the goal of a gap balancing (GB) technique is equal flexion and extension gaps secondary to soft-tissue balancing, and not necessarily component alignment, variation in component placement may exist. Our purpose was (1) to evaluate precision of component alignment in well-functioning GB TKAs performed without the aid of navigation using computed tomographic evaluation and (2) to determine any relationship between femoral version and/or tibial torsion and TKA component positioning. METHODS: There were 93 well-functioning TKAs performed with an extension gap first GB technique with a minimum 2-year follow-up evaluated using computed tomography to assess component rotational alignment, as well as osseous femoral version and tibial torsion. Femoral and tibial rotational alignment was assessed by previously described methods. RESULTS: The mean Knee Society Score was 185.7 ± 21.7. The mean range of motion was 128.5 ± 7.8°. Femoral posterocondylar axis (relative to the transepicondylar axis) values ranged from -8.3 to 4.1° with a mean of -0.78 ± 2.7° (internal rotation). Mean tibial rotation was 17.2 ± 7.9° internal rotation relative to the tibial tubercle. No correlation was found between native femoral version and femoral component rotational alignment (Pearson's correlation coefficient, r, 0.007). Weak correlation was found between native tibial torsion and tibial component alignment (r = 0.24). CONCLUSION: Despite being only a secondary objective with the GB technique, most components evaluated were within the desired range of rotation. Alignment was not influenced by native osseous rotational geometry. LEVEL OF EVIDENCE: Level III, Retrospective Cohort Study.

Are Body Mass Index Cutoffs Creating Racial, Ethnic, and Gender Disparities in Eligibility for Primary Total Hip and Knee Arthroplasty?

BACKGROUND: Unabated increases in the prevalence of obesity among American adults have disproportionately affected women, Black persons, and Hispanic persons. The purpose of this study was to evaluate for disparity in rates of patient eligibility for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) based on race and ethnicity and gender by applying commonly used body mass index (BMI) eligibility criteria to two large national databases. METHODS: We retrospectively reviewed data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for the years 2015-2019 for primary THA and TKA and the National Health and Nutrition Examination Survey (NHANES) from 2011-2018. Designations of race and ethnicity were standardized between cohorts. BMI cutoffs of <50 kg/m2, <45 kg/m2, <40 kg/m2, and <35 kg/m2 were then applied. Rates of eligibility for surgery were examined for each respective BMI cutoff and stratified by age, race and ethnicity, and gender. RESULTS: 143,973 NSQIP THA patients, 242,518 NSQIP TKA patients, and 13,255 NHANES participants were analyzed. Female patients were more likely to be ineligible for surgery across all cohorts for all modeled BMI cutoffs (P < .001 for all). Black patients had relatively lower rates of eligibility across all cohorts for all modeled BMI cutoffs (P < .0001 for all). Hispanic patients had disproportionately lower rates of eligibility only at a BMI cutoff of <35 kg/m2. CONCLUSION: Using BMI cutoffs alone to determine the eligibility for primary THA and TKA may disproportionally exclude women, Black persons, and Hispanic persons. These data raise concerns regarding further disparity and restriction of arthroplasty care to vulnerable populations that are already marginalized. LEVEL OF EVIDENCE: Retrospective Cohort Study, Level III.

Projected Prevalence of Obesity in Primary Total Knee Arthroplasty: How Big Will the Problem Get?

BACKGROUND: Obesity is a well-established risk factor for complications following primary total knee arthroplasty (TKA). The purpose of this study is to utilize 3 national databases to develop projections of obesity within the general population and primary TKA patients in the United States through 2029. METHODS: Data from the National Surgical Quality Improvement Program (NSQIP), the Behavior Risk Factor Surveillance System (BRFSS), and the National Health and Nutrition Examination Survey were queried for years 1999-2019. Current Procedural Terminology code 27447 was used to identify primary TKA patients in NSQIP. Individuals were categorized according to body mass index (kg/m2) by year: normal weight (≤24.9); overweight (25.0-29.9); obese (30.0-39.9); and morbidly obese (≥40). Multinomial logistic regression was used to project categorical body mass index data for years 2020-2029. RESULTS: A total of 8,372,221 individuals were included (7,986,414 BRFSS, 385,807 NSQIP TKA). From 2011 to 2019, the prevalence of normal weight and overweight individuals declined in the general population (BRFSS) and in primary TKA. Prevalence of obese/morbidly obese individuals increased in the general population from 31% to 36% and in primary TKA from 60% to 64%. Projection models estimate that by 2029, 46% of the general population will be obese/morbidly obese and 69% of primary TKA will be obese/morbidly obese. CONCLUSION: By 2029, we estimate ≥69% of primary TKA to be obese/morbidly obese. Increased resources dedicated to care pathways and research focused on improving outcomes in obese arthroplasty patients will be necessary as this population continues to grow. LEVEL OF EVIDENCE: Level III, Retrospective Cohort Study.

Not all Total Hip and Knee Arthroplasties Are the Same: What Are the Implications in Large Database Studies?

BACKGROUND: The use of claims databases for research after total hip and knee arthroplasty (THA, TKA) has increased exponentially. These studies rely on accurate coding, and inadvertent inclusion of patients with nonroutine indications may influence results. The purpose of this study was to evaluate the complexity of THA and TKA captured by CPT code and determine if complication rates vary based on the indication. METHODS: The NSQIP database was queried using CPT codes 21730 and 27447 to identify patients undergoing THA and TKA from 2018 to 2019. The surgical indication was classified based on the ICD-10 diagnosis code as routine primary, complex primary, inflammatory, fracture, oncologic, revision, infection, or indeterminant. Patient factors and 30-day complications, readmission, reoperation, and wound complications were compared. RESULTS: A total of 86,009 THA patients had 703 ICD-10 diagnosis codes and 91.4% were routine primary indications. Complication rates were: routine primary 7.4%, complex primary 11.3%, inflammatory 12.5%, fracture 23.9%, oncologic 32.4%, revision 26.9%, infection 38.7%, and indeterminant 10.3% (P < .0001). 137,500 TKA patients had 552 ICD-10 diagnosis codes and 96.1% were routine primary cases. Complication rates were: routine primary 5.9%, complex primary 8.0%, inflammatory 7.2%, fracture 38.9%, oncologic 32.7%, revision 13.3%, infection 37.7%, and indeterminant 9.6% (P < .0001). Routine primary arthroplasty had significantly lower rates of reoperation, readmission, and wound complications. CONCLUSION: Using CPT code alone captures 10% of THA and 4% of TKA patients with procedures for nonroutine primary indications. It is essential to recognize identification of patients simply by CPT code has the potential to inadvertently introduce bias, and surgeons should critically assess methods used to define the study populations.

Projected Prevalence of Obesity in Primary Total Hip Arthroplasty: How Big Will the Problem Get?

BACKGROUND: Obesity is associated with higher rates of adverse outcomes following primary total hip arthroplasty (THA). The purpose of this study is to utilize 3 national databases to develop projections of obesity within the general population and primary THA patients in the United States through 2029. METHODS: Data from the National Surgical Quality Improvement Program (NSQIP), the Behavior Risk Factor Surveillance System (BRFSS), and the National Health and Nutrition Examination Survey were queried for years 1999-2019. Current Procedural Terminology code 27130 was used to identify primary THA patients in NSQIP. Individuals were categorized according to body mass index (kg/m2) by year: normal weight (≤24.9); overweight (25.0-29.9); obese (30.0-39.9); and morbidly obese (≥40). Multinomial logistic regression was used to project categorical body mass index data for years 2020-2029. RESULTS: A total of 8,222,013 individuals were included (7,986,414 BRFSS, 235,599 NSQIP THA). From 2011 to 2019, the prevalence of normal weight and overweight individuals declined in the general population (BRFSS) and in primary THA. Prevalence of obese/morbidly obese individuals increased in the general population from 31% to 36% and in primary THA from 42% to 49%. Projection models estimate that by 2029, 46% of the general population will be obese/morbidly obese and 55% of primary THA will be obese/morbidly obese. CONCLUSION: By 2029, we estimate ≥55% of primary THA to be obese/morbidly obese. Increased resources dedicated to care pathways and research focused on improving outcomes in obese arthroplasty patients will be necessary as this population continues to grow. LEVEL OF EVIDENCE: Level III, Retrospective Cohort Study.

A Psycholgical Intervention Delivered by Automated Mobile Phone Messaging Stabilized Hip and Knee Function During the COVID-19 Pandemic: A Randomized Controlled Trial.

BACKGROUND: We conducted a randomized controlled trial to evaluate the effectiveness of acceptance and commitment therapy (ACT) delivered via a mobile phone messaging robot to patients who had their total hip arthroplasty or total knee arthroplasty procedures postponed due to the COVID-19 pandemic. METHODS: Ninety patients scheduled for total hip arthroplasty or total knee arthroplasty who experienced surgical delay due to the COVID-19 pandemic were randomized to the ACT group, receiving 14 days of twice daily automated mobile phone messages, or the control group, who received no messages. Minimal clinically important differences (MCIDs) in preintervention and postintervention patient-reported outcome measures were utilized to evaluate the intervention. RESULTS: Thirty-eight percent of ACT group participants improved and achieved MCID on the Patient-Reported Outcome Measure Information System Physical Health compared to 17.5% in the control group (P = .038; number needed to treat [NNT] 5). For the joint-specific Hip Disability and Osteoarthritis Outcome Score Joint Replacement and Knee Disability and Osteoarthritis Outcome Score Joint Replacement (KOOS JR), 24% of the ACT group achieved MCID compared to 2.5% in the control group (P = .004; NNT 5). An improvement in the KOOS JR was found in 29% of the ACT group compared to 4.2% in the control group (P = .028; NNT 5). Fourteen percent of the ACT group participants experienced a clinical important decline in the KOOS JR compared to 41.7% in the control group (P = .027; NNT 4). CONCLUSION: A psychological intervention delivered via a text messaging robot improved physical function and prevented decline in patient-reported outcome measures in patients who experienced an unexpected surgical delay during the COVID-19 pandemic. LEVEL OF EVIDENCE: 1.

Enhancing the magnetic and inductive heating properties of Fe3O4 nanoparticles via morphology control.

Fe3O4 nanoparticles (NPs) with different shapes have been prepared by a 'solventless' synthesis approach to probe shape anisotropy effects on the magnetic and inductive heating properties. Various shapes including spheres, octahedrons, cubes, rods, wires, and multipods are obtained through alterations in reaction conditions such as the ratio of precursor to surfactant content and heating rate. Magnetic and Mössbauer measurements reveal better stoichiometry in anisotropic-shaped Fe3O4 NPs than that in the spherical and multipod NPs. As a result, the magnetization value of the anisotropic-shaped NPs approaches the value for bulk material (∼86 emu g-1). More surprisingly, the Verwey transition, which is a characteristic phase transition of bulk magnetite structure, is observed near 120 K in the anisotropic-shaped NPs, which further corroborates the fact that these NPs possess better stoichiometry compared to the spherical and multipod-shaped NPs. Other than the improved magnetic properties, these anisotropic-shaped NPs are more effective for hyperthermia applications. For example, compared to the conventional spherical NPs, the nanowires show much higher SAR value up to 846 W g-1, making them a potential candidate for practical hyperthermia treatment. In particular, the octahedral NPs shows an SAR value higher than the same size spherical NPs, which demonstrates the importance of occurrence of the Verwey transition in Fe3O4 NPs for better stoichiometric and higher heating.

Effect of COVID-19 on Hip and Knee Arthroplasty Surgical Volume in the United States.

BACKGROUND: In an effort to help combat the COVID-19 pandemic and preserve essential health care resources, starting in mid-March 2020, surgeons have been instructed to only perform essential surgical procedures. The vast majority of hip and knee arthroplasty surgery does not meet the definition of essential surgery. This study estimated the number of arthroplasty procedures that would be canceled because of these important restrictions. METHODS: The US hip and knee arthroplasty procedure volume projections for 2020 were estimated from four recently published studies. Data from the American Joint Replacement Registry were utilized to determine what percentage of these cases would be considered nonessential surgery. Monthly and weekly estimates of nonessential hip and knee arthroplasty procedures that would have occurred had there not been any restrictions due to COVID-19 were calculated. RESULTS: After excluding essential procedures, it was estimated that approximately 30,000 primary and 3000 revision hip and knee arthroplasty procedures will be canceled each week while COVID-19 restrictions regarding nonessential surgery are in place. If only 50% of nonessential cases were actually canceled across the United States, that would still result in the cancellation of 15,001 primary and 1435 revision hip and knee arthroplasty procedures per week while restrictions are in place. CONCLUSION: This study highlights the profound impact COVID-19 is having on our current hip and knee arthroplasty volume. The large number of cases canceled because of COVID-19 translates into major financial losses for health care institutions and may have a profound impact on our patients.

Total Joint Arthroplasty in the Morbidly Obese: How Body Mass Index ≥40 Influences Patient Retention, Treatment Decisions, and Treatment Outcomes.

BACKGROUND: The United States is in an obesity epidemic. Obesity has multiple common comorbid conditions, including lower extremity arthritis. We sought to examine the course of treatment for a population with body mass index (BMI) ≥40 kg/m2 and osteoarthritis (OA) of the hip or knee. We investigated decision criteria that influenced arthroplasty surgeons to recommend nonoperative management vs total joint arthroplasty (TJA). For those patients who ultimately received TJA, we compared outcomes in this population to those with BMI <40 kg/m2. METHODS: This study retrospectively reviewed 158 new patients with BMI ≥40 kg/m2 and moderate/severe OA of the hip or knee. Demographics, comorbidity profiles, and weight loss were compared between groups that underwent TJA and those that did not. The arthroplasty database was used to identify patients who underwent TJA during 2016-2018 (N = 1473). Comorbidities, readmissions, surgical site infections, and overall complications were compared between those with BMI ≥40 kg/m2 and BMI <40 kg/m2. RESULTS: About 51.3% of new patients with BMI ≥40 kg/m2 and moderate/severe OA did not return for a second clinic visit. Of those who did return, 42.9% eventually underwent surgery. BMI was higher in single visit patients vs those with multiple visits (49.5 vs 46.3 kg/m2, P < .001), no difference in those scheduled on an "as-needed" basis vs a specific return date (P = .18), and did not change significantly during the 2-year follow-up (P = .41). Patients who underwent TJA had a lower mean BMI at presentation than their nonoperative counterparts (44.5 vs 47.6 kg/m2, P < .01) and demonstrated significant weight loss prior to surgery (44.5 vs 42.6 kg/m2, P < .05). When comparing patients with BMI ≥40 kg/m2 vs BMI <40 kg/m2, overall complications were not higher in the BMI ≥40 kg/m2 group, although surgical site infections were higher in those undergoing total hip arthroplasty with BMI ≥40 kg/m2 (0.3% vs 3.1%, P < .05). CONCLUSION: A majority of patients with BMI ≥40 kg/m2 and moderate/advanced OA will be lost to orthopedic follow-up. A relatively lower BMI indicates a greater chance of retention in care, and ultimately surgery, but does not influence surgeons' recommendations to continue orthopedic management. Patients who persist in seeking treatment, lose significant weight, and exhaust nonoperative alternatives may be suitable for TJA despite a BMI ≥40 kg/m2, with an overall complication rate of 4.3%. However, only 9% of patients at 2-year follow-up achieved BMI <40 kg/m2 and only 20% of surgeries were performed on patients who had achieved this proposed cutoff.

Reliability of Spinopelvic Measurements That May Influence the Cup Position in Total Hip Arthroplasty.

BACKGROUND: Spinopelvic pathology has been identified as a potential risk factor for instability after total hip arthroplasty. Spinopelvic radiographic parameters used to diagnose spinopelvic disease may also impact optimal cup placement. The purpose of this study was to assess the arthroplasty surgeon accuracy in making spinopelvic measurements. METHODS: Five fellowship-trained or in-training arthroplasty surgeons reviewed 44 lateral lumbar radiographs in two sessions. All evaluators were instructed how to perform measurements but had little experience in doing so. Traditional measurements included the pelvic tilt (PT), pelvic incidence (PI), and sacral slope (SS), and novel measurements included the acetabular ante-inclination (AI) and pelvic femoral angle. Surgeon measurements were compared with those made by experienced engineers. intraclass coefficients (ICCs) were calculated and interpreted. RESULTS: The interobserver reliability for 4 of 5 of the spinopelvic parameters was good to excellent (ICC >0.75) with the highest reliability seen for PI measurement (ICC = 0.939). Only moderate interobserver reliability was observed for AI measurement (ICC = 0.559). Intraobserver reliability was the highest for the PI and SS, ranging from moderate to good (ICC, 0.718 to 0.896). The lowest intraobserver reliability was seen for the AI (ICC range, 0.026 to 0.545) and pelvic femoral angle (ICC range, 0.035 to 0.828). Surgeon measurements of PT and SS were compared with engineer measurements with extremely poor correlation observed (ICC <0 for all). CONCLUSION: Surgeon intraobserver and interobserver reliability in making novel radiographic measurements was low compared with traditional radiographic measurements. Surgeon reliability in making traditional measurements of the PT and SS was very poor compared with experienced assessors using software-based measurements.

Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.

BACKGROUND: Daclizumab high-yield process (HYP) is a humanized monoclonal antibody that binds to CD25 (alpha subunit of the interleukin-2 receptor) and modulates interleukin-2 signaling. Abnormalities in interleukin-2 signaling have been implicated in the pathogenesis of multiple sclerosis and other autoimmune disorders. METHODS: We conducted a randomized, double-blind, active-controlled, phase 3 study involving 1841 patients with relapsing-remitting multiple sclerosis to compare daclizumab HYP, administered subcutaneously at a dose of 150 mg every 4 weeks, with interferon beta-1a, administered intramuscularly at a dose of 30 µg once weekly, for up to 144 weeks. The primary end point was the annualized relapse rate. RESULTS: The annualized relapse rate was lower with daclizumab HYP than with interferon beta-1a (0.22 vs. 0.39; 45% lower rate with daclizumab HYP; P<0.001). The number of new or newly enlarged hyperintense lesions on T2-weighted magnetic resonance imaging (MRI) over a period of 96 weeks was lower with daclizumab HYP than with interferon beta-1a (4.3 vs. 9.4; 54% lower number of lesions with daclizumab HYP; P<0.001). At week 144, the estimated incidence of disability progression confirmed at 12 weeks was 16% with daclizumab HYP and 20% with interferon beta-1a (P=0.16). Serious adverse events, excluding relapse of multiple sclerosis, were reported in 15% of the patients in the daclizumab HYP group and in 10% of those in the interferon beta-1a group. Infections were more common in the daclizumab HYP group than in the interferon beta-1a group (in 65% vs. 57% of the patients, including serious infection in 4% vs. 2%), as were cutaneous events such as rash or eczema (in 37% vs. 19%, including serious events in 2% vs. <1%) and elevations in liver aminotransferase levels that were more than 5 times the upper limit of the normal range (in 6% vs. 3%). CONCLUSIONS: Among patients with relapsing-remitting multiple sclerosis, daclizumab HYP showed efficacy superior to that of interferon beta-1a with regard to the annualized relapse rate and lesions, as assessed by means of MRI, but was not associated with a significantly lower risk of disability progression confirmed at 12 weeks. The rates of infection, rash, and abnormalities on liver-function testing were higher with daclizumab HYP than with interferon beta-1a. (Funded by Biogen and AbbVie Biotherapeutics; DECIDE ClinicalTrials.gov number, NCT01064401.).

Improved cognitive outcomes in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta: Results from the DECIDE study.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain. OBJECTIVE: Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT). METHODS: In DECIDE, patients with relapsing-remitting multiple sclerosis (RRMS) (age: 18-55 years; Expanded Disability Status Scale (EDSS) score 0-5.0) were randomized to daclizumab beta ( n = 919) or IM IFN beta-1a ( n = 922) for 96-144 weeks. SDMT was administered at baseline and at 24-week intervals. RESULTS: At week 96, significantly greater mean improvement from baseline in SDMT was observed with daclizumab beta versus IM IFN beta-1a ( p = 0.0274). Significantly more patients treated with daclizumab beta showed clinically meaningful improvement in SDMT (increase from baseline of ⩾3 points ( p = 0.0153) or ⩾4 points ( p = 0.0366)), and significantly fewer patients showed clinically meaningful worsening (decrease from baseline of ⩾3 points ( p = 0.0103)). Odds representing risk of worsening versus stability or improvement on SDMT were significantly smaller for daclizumab beta ( p = 0.0088 (3-point threshold); p = 0.0267 (4-point threshold)). In patients completing 144 weeks of treatment, the effects of daclizumab beta were generally sustained. CONCLUSION: These results provide evidence for a benefit of daclizumab beta versus IM IFN beta-1a on cognitive processing speed in RRMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01064401 (Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon ß 1a in Participants With Relapsing-Remitting Multiple Sclerosis (DECIDE)): https://clinicaltrials.gov/ct2/show/NCT01064401 .

Lower Extremity Geometry in Morbid Obesity-Considerations for Total Knee Arthroplasty.

BACKGROUND: Obesity has been associated with varying adverse outcomes related to total knee arthroplasty (TKA) and has long been associated with various mechanical complications. Computational modeling holds promise for investigating biomechanical aberrations related to TKA in obese patients. However, basic anthropometric information regarding the shape of the lower extremity in obese patients is lacking. We, therefore, developed a method to determine lower extremity shape both generally and subject specific as a function of body mass index (BMI) and sex. METHODS: A unique set of 4 radiographs (knee anteroposterior/lateral; EOS long-leg alignment anteroposterior/lateral) were reviewed for patients with BMI exceeding 30 kg/m2 before undergoing TKA. Soft tissue thickness in both the coronal and sagittal planes, including anterior adipose tissue thickness overlying the tibial tubercle and patella, was measured. Elliptical parameters were then determined for any distance along the lower extremity. Additional measurements were obtained, including prepatellar thickness and pretubercular thickness and anteroposterior and mediolateral dimensions of the proximal tibia. A total of 232 obese subjects were analyzed. RESULTS: Girth increased as a function of BMI. Anterior prepatellar and pretubercular subcutaneous fat thickness in females exceeded that in males for all values of BMI. Wide variation was seen with regard to overall patterns of adiposity among same-sex subjects with similar BMI. Proximal tibial osseous dimensions did not demonstrate an association with BMI; however, males were found to have deeper and wider tibias compared with females. CONCLUSIONS: BMI and sex influence lower extremity shape. The prediction algorithms developed here holds implications for future biomechanical studies of TKA in obese patients.

Complications and Obesity in Arthroplasty-A Hip is Not a Knee.

BACKGROUND: Obesity has previously been demonstrated to be an independent risk factor for increased complications after total hip and knee arthroplasties (THA and TKA). The purpose of this study was to compare the effects of obesity and body mass index (BMI) to determine whether the magnitude of the effect was similar for both procedures. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who underwent primary THA or TKA between 2010 and 2014. Patients were stratified by procedure and classified as nonobese, obese, or morbidly obese according to BMI. Thirty-day rates of wound complications, deep infection, total complications, and reoperation were compared using univariate and multivariate logistic regression analyses. RESULTS: We identified 64,648 patients who underwent THA and 97,137 patients who underwent TKA. Obese THA patients had significantly higher rates of wound complications (1.53% vs 0.96%), deep infection (0.31% vs 0.17%), reoperation rate (2.11% vs 1.02%), and total complications (5.22% vs 4.63%) compared with TKA patients. Morbidly obese patients undergoing THA were also found to have significantly higher rates of wound complications (3.25% vs 1.52%), deep infection (0.84% vs 0.23%), reoperation rate (3.65% vs 1.60%), and total complications (7.36% vs 5.57%). Multivariate regression analysis identified increasingly higher odds of each outcome measure as BMI increased. CONCLUSION: This study demonstrates that the impact of obesity on postoperative complications is more profound for THA than TKA. This emphasizes the importance of considering patient comorbidities in the context of the specific procedure when assessing risks of surgery.

In vivo maintenance of human regulatory T cells during CD25 blockade.

Regulatory T cells (Tregs) mediate immune tolerance to self and depend on IL-2 for homeostasis. Treg deficiency, dysfunction, and instability are implicated in the pathogenesis of numerous autoimmune diseases. There is considerable interest in therapeutic modulation of the IL-2 pathway to treat autoimmunity, facilitate transplantation tolerance, or potentiate tumor immunotherapy. Daclizumab is a humanized mAb that binds the IL-2 receptor a subunit (IL-2R a or CD25) and prevents IL-2 binding. In this study, we investigated the effect of daclizumab-mediated CD25 blockade on Treg homeostasis in patients with relapsing-remitting multiple sclerosis. We report that daclizumab therapy caused an ~50% decrease in Tregs over a 52-wk period. Remaining FOXP3+ cells retained a demethylated Treg-specific demethylated region in the FOXP3 promoter, maintained active cell cycling, and had minimal production of IL-2, IFN- g, and IL-17. In the presence of daclizumab, IL-2 serum concentrations increased and IL-2R bg signaling induced STAT5 phosphorylation and sustained FOXP3 expression. Treg declines were not associated with daclizumab-related clinical benefit or cutaneous adverse events. These results demonstrate that Treg phenotype and lineage stability can be maintained in the face of CD25 blockade.

The John N. Insall Award: Do Intraarticular Injections Increase the Risk of Infection After TKA?

BACKGROUND: Infection after total knee arthroplasty (TKA) can result in disastrous consequences. Previous research regarding injections and risk of TKA infection have produced conflicting results and in general have been limited by small cohort size. QUESTIONS/PURPOSES: The purpose of this study was to evaluate if intraarticular injection before TKA increases the risk of postoperative infection and to identify if time between injection and TKA affect the risk of TKA infection. METHODS: The Humana data set was reviewed from 2007 to 2014 for all patients who received a knee injection before TKA. Current Procedural Terminology (CPT) codes and laterality modifiers were used to identify patients who underwent knee injection followed by ipsilateral TKA. Postoperative infection within 6 months of TKA was identified using International Classification of Diseases, 9th Revision/CPT codes that represent two infectious endpoints: any postoperative surgical site infection (encompasses all severities of infection) and operative intervention for TKA infection (surrogate for deep TKA infection). The injection cohort was stratified into 12 subgroups by monthly intervals out to 12 months corresponding to the number of months that had elapsed between injection and TKA. Risk of postoperative infection was compared between the injection and no injection cohorts. In total, 29,603 TKAs (35%) had an injection in the ipsilateral knee before the TKA procedure and 54,081 TKA cases (65%) did not. The PearlDiver database does not currently support line-by-line output of patient data, and so we were unable to perform a multivariate analysis to determine whether other important factors may have varied between the study groups that might have had a differential influence on the risk of infection between those groups. However, the Charlson Comorbidity index was no different between the injection and no injection cohorts (2.9 for both) suggesting similar comorbidity profiles between the groups. RESULTS: The proportion of TKAs developing any postoperative infection was higher among TKAs that received an injection before TKA than in those that did not (4.4% versus 3.6%; odds ratio [OR], 1.23; 95% confidence interval [CI], 1.15-1.33; p < 0.001). Likewise, the proportion of TKAs developing infection resulting in return to the operating room after TKA was also higher among TKAs that received an injection before TKA than those that did not (1.49% versus 1.04%; OR, 1.4; 95% CI, 1.3-1.63; p < 0.001). Month-by-month analysis of time between injection and TKA revealed the odds of any postoperative infection remained higher for the injection cohort out to a duration of 6 months between injection and TKA (ORs ranged 1.23 to 1.46 when 1-6 months between injection and TKA; p < 0.05 for all) as did the odds of operative intervention for TKA infection when injection occurred within 7 months of TKA (OR ranged from 1.38 to 1.88 when 1-7 months between injection and TKA; p < 0.05 for all). When the duration between injection and TKA was longer than 6 or 7 months, the ORs were no longer elevated at these endpoints, respectively. CONCLUSIONS: Injection before TKA was associated with a higher risk of postoperative infection and appears to be time-dependent with closer proximity between injection and TKA having increased odds of infection. Further research is needed to better evaluate the risk injection before TKA poses for TKA infection; a more definitive relationship could be established with a multivariate analysis to control for other known risk factors for TKA infection. LEVEL OF EVIDENCE: Level III, therapeutic study.

Exposure-disease response analysis of natalizumab in subjects with multiple sclerosis.

Natalizumab, a human immunoglobulin monoclonal antibody that targets α4ß1/α4ß7 integrin, is an effective therapy approved for the treatment of multiple sclerosis (MS). The objective of this analysis was to develop a population exposure-response model utilizing gadolinium-enhancing (Gd) lesion count data from four clinical studies and annualized relapse rate (ARR) data from three clinical studies. The natalizumab exposures were derived for the individuals using a population pharmacokinetic model. A log-linear exposure effect on Gd lesion count and ARR adequately characterized the relationship between exposure and disease response. In the case of the Gd lesion count model, a bimodal model that distributed subjects into two subpopulations based on low or high baseline Gd lesion count provided a superior goodness of fit. The mean (95% confidence interval) slopes from the exposure-Gd lesion count model and exposure-ARR model are -0.0903 (-0.100, -0.081) and -0.0222 (-0.026, -0.015) (mg/L)-1, respectively. From these slopes, it can be inferred that both Gd lesion count and ARR decrease with increasing exposure to natalizumab in MS subjects. Model-based simulations demonstrated that although reductions in Gd lesion count and ARR were observed with lower doses (75, 150, or 200 mg), only the dose of 300 mg every 4 weeks (q4w) was associated with an ARR ≤0.25 and was considered clinically effective. The results from the exposure-Gd lesion count and exposure-ARR models thus support the appropriateness of the approved natalizumab dose (300 mg q4w) in MS subjects.

Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial.

BACKGROUND: Mobility impairment is a common disability in MS and negatively impacts patients' lives. OBJECTIVE: Evaluate the effect of prolonged-release (PR) fampridine (extended-release dalfampridine in the United States) on self-assessed walking disability, dynamic/static balance and safety in patients with MS. METHODS: MOBILE was a randomised, double-blind, exploratory, placebo-controlled trial. Patients with progressive/relapsing-remitting MS and Expanded Disability Status Scale score of 4.0-7.0 were treated with PR-fampridine or placebo twice daily for 24 weeks. Efficacy endpoints included change from baseline in the 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) test and Berg Balance Scale (BBS). RESULTS: 132 patients were randomised at 24 sites in six countries. PR-fampridine therapy resulted in greater median improvements from baseline in MSWS-12 score, TUG speed and BBS total score versus placebo over 24 weeks. A higher proportion of patients receiving PR-fampridine versus placebo experienced significant improvements at MSWS-12 improvement thresholds ⩾7 (p = 0.0275), ⩾8 (p = 0.0153) and ⩾9 points (p = 0.0088) and TUG speed thresholds ⩾10% (p = 0.0021) and ⩾15% (p = 0.0262). PR-fampridine was well tolerated. CONCLUSIONS: PR-fampridine therapy resulted in early and sustained improvements in broad measures of walking and balance over six months.