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Conventional quantitative diffusion-weighted imaging (DWI) is sensitive to changes in tissue microstructure, but its application to evaluating patients with orthopaedic hardware has generally been limited due to metallic susceptibility artifacts. The apparent diffusion coefficient (ADC) and TCoronal morphologic MRIs from THA patients underwent evaluation of the synovium and were assigned a synovial classification of 'normal', or 'grouped abnormal' (consisting of sub-groups 'infection', 'polymeric', 'metallosis', 'adverse local tissue reaction' [ALTR], or 'non-specific') and type of synovial reaction present (fluid-like, solid-like, or mixed). Regions of interest (ROIs) were placed in synovial reactions for measurement of ADC and TDifferences of ADC and T2D-MSI PROPELLER DWI and MAVRIC-T

Background Because loosening of total knee arthroplasty (TKA) occurs due to poor osseous integration at component-bone interfaces, interface assessment may be helpful in diagnosing loosening at MRI. Purpose To determine interreader reproducibility for characterizing component interfaces and diagnosing loosening and to evaluate the diagnostic performance of MRI for diagnosing loosening after TKA compared with radiography. Materials and Methods Consecutive knees with TKA that underwent revision between July 2018 and June 2019 and were imaged at MRI and radiography were included in this retrospective study. Interface type (normal, fibrous membrane, fluid, or osteolysis), percent integration (33%, 33%-66%, or66%), and presence of bone marrow edema pattern were assessed. Loosening was diagnosed at MRI if no or almost no normal interface was present. Sensitivity and specificity were compared with radiographs by using surgical findings as reference. Gwet agreement coefficient evaluated interreader reproducibility between two readers and multivariable logistic regression assessed risk factors for loosening. Results Among 116 knees in 114 patients (mean age, 63 years ± 10 [SD]; 59 women), 61 of 116 knees (52.6%) had at least one loose component. Interreader reproducibility of MRI was substantial to excellent (Gwet agreement coefficient, 0.67-0.96). Loosening was associated with fluid interface (odds ratio [OR], 20.1; 95% CI: 5.7, 70.9) or osteolysis (OR, 3.1; 95% CI: 1.8, 5.3), absence of any normal interface (OR, 11.8; 95% CI: 6.3, 22.2), poor (33%) osseous integration (OR, 20.4; 95% CI: 9.7, 42.6), and bone marrow edema pattern (OR, 4.7; 95% CI: 2.8, 7.8). Sensitivity and specificity of MRI for loosening were 84% (27 of 32; 95% CI: 72, 97) and 85% (71 of 84; 95% CI: 77, 92) for the patellar, 31% (eight of 26; 95% CI: 13, 49) and 100% (90 of 90; 95% CI: 100, 100) for the femoral, and 81% (22 of 27; 95% CI: 66, 96) and 98% (87 of 89; 95% CI: 95, 100) for the tibial component, respectively. MRI had higher sensitivity (84% vs 31%

Scholars have recently begun reexamining the Whig Party, paying particular attention to how the party gained adherents and challenged Andrew Jackson and his acolytes. Yet few scholars have focused attention on the Whig sense of humor. Typically portrayed as more uptight than their rambunctious Democratic counterparts, Whigs were seemingly unable to find humor in a burgeoning democratic society. This article challenges that traditional portrait by examining George D. Prentice, the long-serving editor of the Louisville Journal. Although largely forgotten as a humorist, Prentice gained a national reputation for his “hits” that appeared daily in the pages of the Louisville Journal from 1830 to 1868. By pillorying the opposition party, Prentice found a way to joke about corruption, adultery, drunkenness, and even death. In doing so, Prentice proved that Whigs did have a sense of humor, although it largely consisted of mocking Democrats for their eccentricities and supposed moral failings.

In the nineteenth century, writers such as James Fenimore Cooper and Henry Wadsworth Longfellow wrote best-selling works that shaped popular perceptions of Native American men. Historians and literary scholars have argued that literary characters representing Native men can be classified into two broad categories: Noble Savages and Bloody Savages. This article examines the literary origins and emergence of a third figure: the Comic Indian. Beginning with the various parodies of Longfellow’s Hiawatha in 1855, and continuing through the western humor of Bill Nye, this article examines how writers crafted comic characters that burlesqued stereotypical Native Americans. By the end of the century, the Comic Indian had become standard fare in U.S. literature. Understanding this history helps to explain why certain comic caricatures of Native men have persisted into the present and illustrates that humor can be used to justify genocidal policies.

Background: When patients with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) develop digital ischemia, conventional angiography (CA) is traditionally used to assess hand vasculature. Recently, Chang et al described an angiographic classification system for patients with SSc. Conventional angiography uses intravascular contrast agents that are nephrotoxic and vasoconstrictive. Owing to these limitations, this study assesses the use of contrast-enhanced magnetic resonance angiography (MRA) as an alternative to CA to evaluate hand vasculature in patients with digital ischemia. Methods: This retrospective case series reports on 38 contrast-enhanced MRAs of hand vasculature from 30 symptomatic patients with SSc (N = 21) or SLE (N = 9). The radial and ulnar arteries (RA, UA) and the superficial and deep palmar arches were evaluated at standard reference points both quantitatively and qualitatively for their diameter, patency, and Chang classification. Results: In SSc MRAs (n = 26), the UA was significantly smaller than the RA and was occluded in 46%. In SLE MRAs (n = 12), the UA and RA had no difference in diameter and the UA was occluded in 25%. In SSc, the most common Chang classification was type 2 (UA involvement) in 44%. In SLE, the most common Chang classification was type 4 (UA and RA involvement) in 45%, with 18% classified as type 2. Conclusions: Contrast-enhanced MRA used to assess hand vasculature in SSc patients with digital ischemia shows similar patterns of vascular involvement as previously demonstrated by CA. While vascular involvement in SSc predominantly involves the UA, the RA is also frequently involved in SLE.

BACKGROUND: T(2)-weighted, two-point Dixon fast-spin-echo (FSE) is an effective technique for magnetic resonance neurography (MRN) that can provide quantitative assessment of muscle denervation. Low signal-to-noise ratio and inadequate fat suppression, however, can impede accurate interpretation. PURPOSE: To quantify effects of principal component analysis (PCA) denoising on tissue signal intensities and fat fraction (FF) and to determine qualitative image quality improvements from both denoising and water-weighting (WW) algorithms to improve nerve conspicuity and fat suppression. STUDY TYPE: Prospective. SUBJECTS: Twenty-one subjects undergoing MR neurography evaluation (11/10 male/female, mean age=46.3+/−13.7 years) with 60 image volumes. Twelve subjects (23 image volumes) were determined to have muscle denervation based on diffusely elevated T(2) signal intensity. FIELD STRENGTH/SEQUENCE: 3T, 2D, two-point Dixon FSE. ASSESSMENT: Qualitative assessment included overall image quality, nerve conspicuity, fat suppression, pulsation and ringing artifacts by 3 radiologists separately on a three-point scale (1=poor, 2=average, 3=excellent). Quantitative measurements for FF and signal intensity relative to normal muscle were made for nerve, abnormal muscle and subcutaneous fat. STATISTICAL TESTS: Linear and ordinal regression models were used for quantitative and qualitative comparisons, respectively; 95% confidence intervals (CIs) and p-values for pairwise comparisons were adjusted using the Holm-Bonferroni method. Inter-rater agreement was assessed using Gwet’s agreement coefficient (AC(2)). RESULTS: Simulations showed PCA-denoising reduced FF error from 2.0% to 1.0%, and from 7.6% to 3.1% at noise levels of 10% and 30%, respectively. In human subjects, PCA-denoising did not change signal levels and FF quantitatively. WW decreased fat signal significantly (−83.6%, p

The evaluation of the natural history prevalence of adverse local tissue reactions (ALTRs) using MRI has focused only on metal-on-metal (MoM) bearing surfaces without comparison to nonMoM bearing surfaces.To determine (1) the longitudinal changes and differences in blood metal ion levels in patients with hip resurfacing arthroplasty (HRA), ceramic-on-ceramic (CoC) THA, and metal-on-polyethylene (MoP) THA compared with those undergoing ceramic-on-polyethylene (CoP) THA; (2) how the longitudinal change of synovial reaction classification in patients with HRA, CoC THA, and MoP THA compares with those undergoing CoP THA, and whether there is an association between the presence of an ALTR or metallosis on MRI with corresponding patient-reported outcomes, or the presence of capsular dehiscence; and (3) differences in blood metal ion levels between patients undergoing HRA with an ALTR or metallosis on MRI and those with HRA without these conditions.Between March 2014 and February 2019, 22,723 patients underwent primary HRA and THA at one center. Patients received an HRA based on their desired athletic level after surgery and the presence of normal acetabular and proximal femoral bone morphology without osteopenia or osteoporosis. Two percent (342 of 22,723) of patients were contacted to participate, and 71% (243 of 342 hips in 206 patients) were enrolled for analysis at baseline. The patients underwent arthroplasty for degenerative joint disease, and 25 patients withdrew over the course of the study. We included patients who were more than 1 year postarthroplasty. All participants had an MRI examination and blood serum ion testing and completed a Hip Disability and Osteoarthritis Outcome Score survey annually for four years (baseline, year 1, year 2, year 3). Morphologic and susceptibility-reduced MR images were evaluated by a single radiologist not involved in the care of patients for the presence and classification of synovitis (Gwet AC1: 0.65 to 0.97), synovial thickness, and volume (coefficient of repeatability: 1.8 cm3). Linear mixed-effects models were used to compare the mean synovial thickness, synovial volume, and Hip Disability and Osteoarthritis Outcome Score subscales between bearing surfaces at each timepoint and within each bearing surface over time. Marginal Cox proportional hazards models were used to compare the time to and the risk of developing ALTR only, metallosis only, and ALTR or metallosis between bearing surfaces. All models were adjusted for age, sex, BMI, and length of implantation based on known confounders for hip arthroplasty. Adjustment for multiple comparisons was performed using the Dunnett-Hsu method.Patients with unilateral HRA had higher cobalt and chromium serum ion levels (baseline: 1.8 ± 0.8 ppb, year 1: 2.0 ± 1.5 ppb, year 2: 2.1 ± 1.2 ppb, year 3: 1.6 ± 0.7 ppb) than those with unilateral CoP bearings (baseline: 0.0 ± 0.1 ppb, year 1: 0.1 ± 0.3 ppb, year 2: 0.0 ± 0.2 ppb, year 3: 0.0 ± 0.0 ppb) at all timepoints (p0.001 for each time point). More patients who received an HRA developed ALTR or metallosis on MRI than did patients with CoP bearings (hazard ratio 4.8 [95% confidence interval 1.2 to 18.4]; p = 0.02). There was no association between the longitudinal change of synovial reaction to ALTR or metallosis on MRI with patient-reported outcomes. In addition, there was no association between the presence of dehiscence at baseline and the subsequent development of ALTR or metallosis, as seen on MRI. There were elevated cobalt (4.7 ± 3.5 ppb) and chromium (4.7 ± 2.6 ppb) serum levels in patients with unilateral HRA who had an ALTR or metallosis present on MRI at year 1 compared with patients without an ALTR or metallosis on MRI (cobalt: 1.8 ± 1.0 ppb, mean difference 4.7 ppb [95% CI 3.3 to 6.0]; p0.001; chromium: 2.3 ± 0.5 ppb, mean difference 3.6 ppb [95% CI 2.2 to 5.0]; p0.001) as well as for chromium at year 3 (3.9 ± 2.4 ppb versus 2.2 ± 1.1 ppb, mean difference 1.3 ppb [95% CI 0.3 to 2.4]; p = 0.01).We found a higher proportion of ALTR or metallosis on MRI in patients with HRA compared with patients with CoP, even when patient self-assessed symptomatology of those with an ALTR or metallosis on MRI was not different than the absence of these features. MRI detected ALTRs in high-function patients, emphasizing that an annual clinical assessment dependent on survey or blood ion testing alone may not detect soft tissue complications. The results of this study are in line with prior consensus recommendations of using MRI as part of a routine follow-up protocol for this patient population.Level III, therapeutic study.

Osteoarthritis (OA) is one of the most common causes of disability throughout the world. Current therapeutic strategies are aimed at preventing the development and delaying the progression of OA, as well as repairing or replacing worn articular surfaces, because the regeneration of lost hyaline articular cartilage is not currently a clinically feasible option. Imaging is useful in formulating treatment strategies in patients at risk for OA, allowing assessment of risk factors, the degree of preexisting tissue damage, and posttreatment monitoring. Magnetic resonance imaging (MRI), in particular, provides in-depth evaluation of these patients, with optimal clinical sequencing allowing sensitive assessment of chondral signal and morphology, and the addition of advanced MRI techniques facilitating comprehensive evaluation of joint health, with increased sensitivity for changes in articular cartilage and surrounding joint tissues.

Biologic failures of hip arthroplasty have emerged as an increasing threat to the longevity of the prosthesis. While wear of modern-day bearings has been greatly reduced with the advent of cross-linked polyethylene, local reaction to metal particles either from the bearing itself or to any of the modular tapers appears to be on the rise. Monitoring of these reactions by the use of plain radiographs or serum markers appears to be insufficient to gauge the gravity of the response. Over the past decade, the use of magnetic resonance imaging (MRI) techniques has emerged as the superior noninvasive instrument to assess the extent of soft tissue reaction around hip implants. The use of MRI around implants was initially challenging due to the presence of relatively high ferrous metals especially cobalt which causes local distortion of the magnetic fields. Novel changes in pulse sequencing have greatly improved the sensitivity and specificity of MRI so that at this time, MR is the most predictive diagnostic tool in evaluating the extent of tissue destruction. We feel strongly that modern MRI techniques are the most important tool in the workup of the patient suspected of having an adverse tissue reaction after hip arthroplasty.

Background Femoral exposure for direct anterior approach (DAA) total hip arthroplasty (THA) invariably requires posterior soft tissue releases. Released posterior structures cannot be repaired. The purpose of this study is to describe the frequency and anatomic consequences of DAA THA posterior soft tissue releases and to compare the appearance of the anterior capsule between a group of patients who had capsulotomy and repair versus capsulectomy. Methods Thirty-two DAA THA patients underwent metal artifact reduction sequence magnetic resonance imaging at discharge and 1-year follow-up. Seventeen had underwent capsulotomy and repair and 15 capsulectomy. A radiologist blinded to intraoperative data scored each metal artifact reduction sequence magnetic resonance imaging. Anterior capsular integrity, status of the piriformis and conjoint tendons, and muscle atrophy were graded. Descriptive statistics were performed to analyze results. Results Immediately postoperatively, 75% of piriformis tendons were intact and 38% of conjoined tendons were intact. At 1 year, 97% had an intact piriformis and conjoined tendon, although many were in continuity through scar with the capsule. The posterior capsule directly contacted bone in all patients. At 1 year, none of the patients who underwent capsulotomy with repair had persistent anterior capsule defects, while 27% in the capsulectomy group had persistent defects. Conclusion Posterior capsule and conjoined tendon releases were commonly performed during DAA THA, yet continuity with bone was frequently achieved at 1 year. In this study, capsulotomy with repair resulted in no anterior capsular defects when compared with capsulectomy. These results may support improved THA stability observed after DAA with capsular repair despite posterior soft tissue releases. Level of Evidence Level III, prospective cohort study.

Many advancements have been made in musculoskeletal magnetic resonance imaging (MRI). Initial emphasis placed on diagnostic improvements demonstrated that MR imaging can be used as a means of noninvasive, accurate assessment of joint health. Advances have improved spatial resolution, tissue contrast and imaging speed. In this review we provide background on MR signal generation and decay and the utility of morphological MRI assessments, including descriptions of the MRI appearance of various internal knee derangements such chondral abnormalities, extensor mechanism disorders and various ligament and tendon pathological conditions. Because MR imaging can also be used to noninvasively evaluate the biochemical status of tissues, we also discuss the following quantitative parametric mapping techniques: T2 mapping, T2∗ mapping, T1ρ and delayed gadolinium enhanced MRI of cartilage (dGEMRIC). These quantitative MRI (qMRI) techniques can provide a more sensitive means by which to detect tissue pathological conditions before the manifestation of structural breakdown or gross morphological defects become conspicuous on high-resolution morphological images. As such, qMRI techniques can be used to generate risk assessments for patients with predispositions towards certain musculoskeletal pathological conditions, as well as provide quantitative metrics by which to monitor the progression of disease and evaluate intervention efficacy. Finally, additional advanced MR imaging techniques including zero echo time (ZTE) MRI for the evaluation of cortical bone, and metal artefact reduction techniques (multiacquisition variable-resonance image combination (MAVRIC), SEMAC) are also discussed.

The Fourier transform is defined not only for 1D signals but for functions of arbitrary dimension. Thus, 2D images are nothing special from a mathematical point of view.

Histograms are used to depict image statistics in an easily interpreted visual format. With a histogram, it is easy to determine certain types of problems in an image, for example, it is simple to conclude if an image is properly exposed by visual inspection of its histogram. In fact, histograms are so useful that modern digital cameras often provide a real-time histogram overlay on the viewfinder (Fig. 3.1) to help prevent taking poorly exposed pictures. It is important to catch errors like this at the image capture stage because poor exposure results in a permanent loss of information, which it is not possible to recover later using image-processing techniques. In addition to their usefulness during image capture, histograms are also used later to improve the visual appearance of an image and as a “forensic” tool for determining what type of processing has previously been applied to an image. The final part of this chapter shows how to calculate simple image statistics from the original image, its histogram, or the so-called integral image.

In any application that requires precise, reproducible, and deviceindependent presentation of colors, the use of calibrated color systems is an absolute necessity. For example, color calibration is routinely used throughout the digital print work flow but also in digital film production, professional photography, image databases, etc. One may have experienced how difficult it is, for example, to render a good photograph on a color laser printer, and even the color reproduction on monitors largely depends on the particular manufacturer and computer system.

In eukaryotic cells, reversible attachment of ubiquitin and ubiquitin-like modifiers (Ubls) to specific target proteins is conducted by multicomponent systems whose collective actions control protein fate and cell behaviour in precise but complex ways. In trypanosomatids, attachment of ubiquitin and Ubls to target proteins regulates the cell cycle, endocytosis, protein sorting and degradation, autophagy and various aspects of infection and stress responses. The extent of these systems in trypanosomatids has been surveyed in recent reports, while in Leishmania mexicana, essential roles have been defined for many ubiquitin-system genes in deletion mutagenesis and life-cycle phenotyping campaigns. The first steps to elucidate the pathways of ubiquitin transfer among the ubiquitination components and to define the acceptor substrates and the downstream deubiquitinases are now being taken.

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

BACKGROUND Quantitative diffusion MRI is a promising technique for evaluating peripheral nerve integrity but low signal-to-noise ratio (SNR) can impede measurement accuracy. PURPOSE To evaluate principal component analysis (PCA) and generalized spherical deconvolution (genSD) denoising techniques to improve within-subject reproducibility and peripheral nerve conspicuity. STUDY TYPE Prospective. SUBJECTS Seven healthy volunteers and three peripheral neuropathy patients. FIELD STRENGTH/SEQUENCE 3T/multiband single-shot echo planar diffusion sequence using multishell 55-direction scheme. ASSESSMENT Images were processed using four methods: "original" (no denoising), "average" (10 repetitions), "PCA-only," and "PCA + genSD." Tibial and common peroneal nerve segmentations and masks were generated from volunteer diffusion data. Quantitative (SNR and contrast-to-noise ratio [CNR]) values were calculated. Three radiologists qualitatively evaluated nerve conspicuity for each method. The two denoising methods were also performed in three patients with peripheral neuropathies. STATISTICAL TESTS For healthy volunteers, calculations included SNR and CNRFA (computed using FA values). Coefficient of variation (CV%) of CNRFA quantified within-subject reproducibility. Groups were compared with two-sample t-tests (significance P < 0.05; two-tailed, Bonferroni-corrected). Odds ratios (ORs) quantified the relative rates of each of three radiologists confidently identifying a nerve, per slice, for the four methods. RESULTS "PCA + genSD" yielded the highest SNR (meanoverall = 14.83 ± 1.99) and tibial and common peroneal nerve CNRFA (meantibial = 3.45, meanperoneal = 2.34) compared to "original" (P SNR < 0.001; P CNR = 0.011) and "PCA-only" (P SNR < 0.001, P CNR < 0.001). "PCA + genSD" had higher within-subject reproducibility (low CV%) for tibial (6.04 ± 1.98) and common peroneal nerves (8.27 ± 2.75) compared to "original" and "PCA-only." The mean FA was higher for "original" than "average" (P < 0.001), but did not differ significantly between "average" and "PCA + genSD" (P = 0.14). "PCA + genSD" had higher tibial and common peroneal nerve conspicuity than "PCA-only" (ORtibial = 2.50, P < 0.001; ORperoneal = 1.86, P < 0.001) and "original" (ORtibial = 2.73, P < 0.001; ORperoneal = 2.43, P < 0.001). DATA CONCLUSION PCA + genSD denoising method improved SNR, CNRFA , and within-subject reproducibility (CV%) without biasing FA and nerve conspicuity. This technique holds promise for facilitating more reliable, unbiased diffusion measurements of peripheral nerves. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1128-1137.

We tagged 12 Carcharhinus limbatus with acoustic transmitters and monitored their presence at five piers along the north-east coast of South Carolina, USA in 2016 and four piers in 2017 using acoustic receivers. Data were analysed with pier association indices (PAI), mixed models and fast Fourier transformation analyses to identify potential factors related to residence time and presence at piers and any cyclical patterns in visits to piers. While the majority of monitored C. limbatus were infrequently detected at piers, three (25.0%) were highly associated with piers (PAI ≥ 0.50). Of the C. limbatus that were detected after initial capture, three (25.0%) recorded detection events only at the pier where they were tagged and two individuals (16.7%) recorded at least one detection event at all monitored piers. The best-fit model explaining C. limbatus residence time at piers included terms for pier location and diel cycle (wi = 0.88), whereas the best fit model explaining presence-absence of C. limbatus at piers included terms for tidal height, diel cycle, barometric pressure and angler count (wi = 0.98). Carcharhinus limbatus did not appear to display cyclical patterns in their visits to piers. Along the north-east coast of South Carolina, association of C. limbatus with piers is a phenomenon for a proportion of mature individuals, but continued research is necessary to understand if this behaviour is driven by attraction to and feeding on angler discards or increased foraging opportunities resulting from the attraction of potential prey to the physical structure provided by piers.

Background Both reduced glomerular filtration rate and increased urine albumin excretion, markers of chronic kidney disease (CKD), are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). However, CKD is not recognized as an ASCVD risk equivalent by most lipid guidelines. Statin medications, especially when combined with ezetimibe, significantly reduce ASCVD risk in patients with nondialysis-dependent CKD. Unless physicians recognize the heightened ASCVD risk in this population, statins may not be prescribed in the absence of clinical cardiovascular disease or diabetes, a recognized ASCVD risk equivalent. We examined statin use in adults with nondialysis-dependent CKD and examined whether the use differed in the presence of clinical ASCVD and diabetes. Methods This study ascertained statin use from pharmacy dispensing records during fiscal years 2012 and 2013 from the US Department of Veterans Affairs Healthcare System. The study included 581 344 veterans aged ≥50 years with nondialysis-dependent CKD Stages 3–5 with no history of kidney transplantation or dialysis. The 10-year predicted ASCVD risk was calculated with the pooled risk equation. Results Of veterans with CKD, 62.1% used statins in 2012 and 55.4% used statins continuously over 2 years (2012–13). Statin use in 2012 was 76.2 and 75.5% among veterans with CKD and ASCVD or diabetes, respectively, but in the absence of ASCVD, diabetes or a diagnosis of hyperlipidemia, statin use was 21.8% (P Conclusions Statin use is low in veterans with nondialysis-dependent CKD in the absence of ASCVD or diabetes despite high-predicted ASCVD risk. Future studies should examine other populations.

Background:Poor osseous integration after fresh osteochondral allograft transplantation (OCA) may be associated with graft subsidence and subchondral bone collapse after implantation. The augmentation of OCA with bone marrow aspirate concentrate (BMAC) has been hypothesized to improve osseous incorporation of the implanted allograft.Purpose:To evaluate the effect of autogenous BMAC treatment on osseous integration at the graft-host bony interface after OCA.Study Design:Cohort study; Level of evidence, 3.Methods:A retrospective review of patients treated with OCA+BMAC or OCA alone for full-thickness chondral defects of the distal femur from March 2015 to December 2016 was conducted. Seventeen knees treated with OCA+BMAC and 16 knees treated with OCA alone underwent magnetic resonance imaging (MRI) in the early postoperative phase (mean, 6 months). Eighteen knees treated with OCA+BMAC and 16 knees treated with OCA alone underwent MRI in the late postoperative phase (mean, 12 months). Bone, cartilage, and ancillary features on MRI were graded using the Osteochondral Allograft MRI Scoring System (OCAMRISS) by a musculoskeletal radiologist blinded to the patient’s history and treatment.Results:There were no significant differences in the demographics or lesion characteristics between treatment groups in either postoperative phase. In the early postoperative phase, the mean OCAMRISS bone score was 3.0 ± 0.7 and 3.3 ± 0.7 for the OCA+BMAC group and OCA alone group, respectively ( P = .76); 71% (OCA+BMAC) and 81% (OCA alone) of MRI scans demonstrated discernible clefts at the graft-host junction ( P = .69), and 41% (OCA+BMAC) and 25% (OCA alone) of MRI scans demonstrated cystic changes at the graft and graft-host junction ( P = .46). In the late postoperative phase, the mean OCAMRISS bone score was 2.7 ± 0.8 and 2.9 ± 0.8 for the OCA+BMAC group and OCA alone group, respectively ( P = .97); 44% (OCA+BMAC) and 63% (OCA alone) of MRI scans demonstrated discernible clefts at the graft-host junction ( P = .33), and 50% (OCA+BMAC) and 31% (OCA alone) of MRI scans demonstrated the presence of cystic changes at the graft and graft-host junction ( P = .32). The mean OCAMRISS cartilage, ancillary, and total scores were not significantly different between groups in either postoperative phase.Conclusion:OCA augmented with BMAC was not associated with improved osseous integration; decreased cystic changes; or other bone, cartilage, and ancillary feature changes compared with OCA alone.

Early attempts at systematic assessment of patient outcomes focused on easily measurable, objective observations of clinical failure: surgical site infection, implant failure, revision surgery, or even death. These outcomes are still reported today as they remain objectively observable evidence of failure of surgical treatment. But how do we measure success? This is a particularly important question for cartilage repair where the evaluation of novel approaches, such as the implantation of stem cells, scaffolds, or other biologics against existing treatments, remains a significant hurdle for clinical development. The innovation of therapies for cartilage repair remains an active area of research because current treatments such as microfracture, tissue grafting, and chondrocyte transplantation do not lead to the formation of tissue with the normal, complex architecture of native articular cartilage within a treated lesion. Yet we have to understand whether and how tissue quality correlates with clinical treatment success, which considers such factors as return to full, pain-free activity and forestalling the progression to degenerative arthritis in the affected joint. Here, we review the most relevant outcome assessment tools for successful cartilage repair.

Background: Sacroiliac (SI) joint subchondral resorption on high-resolution magnetic resonance imaging (MRI) may be an early sign of the development of sacroiliitis. At our institution, high-resolution intermediate-weighted (proton density) MRI sequences are used in the workup of suspected spondyloarthritis (SpA). Questions/Purpose: We sought to test the hypothesis that SI joint subchondral resorption might be a useful MRI feature in the diagnosis of sacroiliitis. Methods: We retrospectively reviewed the records of patients with suspected SpA from a single rheumatologist’s practice from January 1, 2010, to December 31, 2017. Patients had an MRI of the SI joints, using our institution’s specialized protocol, and underwent standard physical examination and laboratory evaluation. The sensitivity and specificity of SI joint subchondral resorption in the identification of sacroiliitis were estimated using the clinical diagnosis as the reference standard and from a Bayesian latent class model with conditional dependence. Results: SI joint subchondral resorption on SI joint MRI was highly correlated with a positive diagnosis in patients worked up for axial SpA. It demonstrated superior sensitivity when compared with other MRI features used in the MRI diagnosis of sacroiliitis, such as bone marrow edema pattern, erosion, and ankylosis. Interobserver reliability was high for subchondral resorption. Conclusion: This retrospective study found that subchondral resorption on MRI evaluation of the SI joints appeared to be a sensitive indicator of SpA, potentially of early disease. This imaging feature warrants evaluation in other cohorts of patients suspected of having axial SpA to validate diagnostic performance in diverse populations.

Background: Hip arthroplasty is increasingly prevalent, and early detection of complications can improve outcomes. Quantitative magnetic resonance imaging (qMRI) methods using multi-acquisition variable-resonance image combination (MAVRIC) may allow for the assessment of soft tissues in close proximity to hip arthroplasty devices. Question/Purposes: We sought to determine the clinical feasibility of MAVRIC-based T2 mapping as a qMRI approach for assessing synovial reactions in patients with a hip arthroplasty device. We hypothesized that there would be differences in T2 metrics by synovial type, clinical impression, and clinical findings related to synovitis. Methods: We conducted a cross-sectional study of 141 subjects with 171 hip arthroplasties with greater than 1 year post-implantation. We enrolled subjects who had had a primary total hip arthroplasty or hip resurfacing arthroplasty between May 2019 and March 2020, excluding those with a revision hip arthroplasty and those with standard safety contraindications for receiving an MRI. Institutional standard 2D fast spin echo (FSE), short-tau inversion recovery (STIR), and susceptibility-reduced MAVRIC morphological MR images were acquired for each hip and followed by a dual-echo acquisition MAVRIC T2 mapping sequence. Results: While 131 subjects (81%) were classified as having a “normal” synovial reaction, significantly longer T2 values were found for fluid synovial reactions compared with mixed reactions. In addition, subjects with synovial dehiscence and decompression present had T2 prolongation. Larger synovial volumes were found in subjects with low-signal intensity deposits. Conclusions: MAVRIC-based T2 mapping is clinically feasible and there are significant quantitative differences based on type of synovial reaction. Patients undergoing hip arthroscopy revision surgery will warrant comparison of T2 values with direct histologic assessment of a tissue sample obtained intraoperatively. The approach used in this study may be used for a quantitative evaluation and monitoring of soft tissues around metal implants.

Background: Fresh osteochondral allograft transplant (OCA) has good outcomes in the knee. However, donor tissue for patellar OCA is limited. Outcomes after nonorthotopic OCA of the patella using more readily available femoral condylar allograft (FCA) tissue have not been previously reported. Purpose: To assess short-term magnetic resonance imaging (MRI) and minimum 2-year clinical outcomes of nonorthotopic patellar OCA using an FCA donor. Study Design: Case series; Level of evidence, 4. Methods: A prospective institutional cartilage registry was reviewed to identify patients treated with patellar OCA using an FCA donor between August 2009 and June 2016. OCA plugs were obtained from the FCA at its trochlear-condylar junction and implanted into the recipient patellar lesion. Early postoperative MRI scans were graded by a blinded musculoskeletal radiologist using the Osteochondral Allograft MRI Scoring System (OCAMRISS). International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), Knee Outcomes Survey–Activities of Daily Living (KOS-ADL), and pain visual analog scale (VAS) scores were collected preoperatively and at minimum 2 years postoperatively, and outcomes were compared using the paired t test. Results: A total of 25 patients were included for clinical outcome analysis and 20 patients for MRI analysis. MRI scans obtained at a mean of 11.4 months (range, 6-22 months) postoperatively showed a mean total OCAMRISS score of 9.0 (range, 7-11); mean bone, cartilage, and ancillary subscores were 2.6, 3.7, and 2.6, respectively. At the latest follow-up (mean, 46.5 months; range, 24-85 months), postoperative improvements were noted in IKDC (from 45.0 to 66.2; P = .0002), KOS-ADL (from 64.3 to 80.4; P = .0012), and VAS (from 5.1 to 3.4; P = .001) scores, with IKDC and KOS-ADL scores above the corresponding previously reported minimal clinically important difference. Conclusion: In this study, patellar OCA using nonorthotopic FCA led to significant short-term improvements in pain and patient-reported outcomes. The majority of nonorthotopic patellar grafts demonstrated full osseous incorporation and good restoration of the articular surface on MRI at short-term follow-up.

Post-translational modifications such as ubiquitination are important for orchestrating the cellular transformations that occur as the Leishmania parasite differentiates between its main morphological forms, the promastigote and amastigote. 2 E1 ubiquitin-activating (E1), 13 E2 ubiquitin-conjugating (E2), 79 E3 ubiquitin ligase (E3) and 20 deubiquitinating cysteine peptidase (DUB) genes can be identified in the Leishmania mexicana genome but, currently, little is known about the role of E1, E2 and E3 enzymes in this parasite. Bar-seq analysis of 23 E1, E2 and HECT/RBR E3 null mutants generated in promastigotes using CRISPR-Cas9 revealed numerous loss-of-fitness phenotypes in promastigote to amastigote differentiation and mammalian infection. The E2s UBC1/CDC34, UBC2 and UEV1 and the HECT E3 ligase HECT2 are required for the successful transformation from promastigote to amastigote and UBA1b, UBC9, UBC14, HECT7 and HECT11 are required for normal proliferation during mouse infection. Of all ubiquitination enzyme null mutants examined in the screen, Δubc2 and Δuev1 exhibited the most extreme loss-of-fitness during differentiation. Null mutants could not be generated for the E1 UBA1a or the E2s UBC3, UBC7, UBC12 and UBC13, suggesting these genes are essential in promastigotes. X-ray crystal structure analysis of UBC2 and UEV1, orthologues of human UBE2N and UBE2V1/UBE2V2 respectively, reveal a heterodimer with a highly conserved structure and interface. Furthermore, recombinant L. mexicana UBA1a can load ubiquitin onto UBC2, allowing UBC2-UEV1 to form K63-linked di-ubiquitin chains in vitro. Notably, UBC2 can cooperate in vitro with human E3s RNF8 and BIRC2 to form non-K63-linked polyubiquitin chains, showing that UBC2 can facilitate ubiquitination independent of UEV1, but association of UBC2 with UEV1 inhibits this ability. Our study demonstrates the dual essentiality of UBC2 and UEV1 in the differentiation and intracellular survival of L. mexicana and shows that the interaction between these two proteins is crucial for regulation of their ubiquitination activity and function., Author summary The post-translational modification of proteins is key for allowing Leishmania parasites to transition between the different life cycle stages that exist in its insect vector and mammalian host. In particular, components of the ubiquitin system are important for the transformation of Leishmania from its insect (promastigote) to mammalian (amastigote) stage and normal infection in mice. However, little is known about the role of the enzymes that generate ubiquitin modifications in Leishmania. Here we characterise 28 enzymes of the ubiquitination pathway and show that many are required for life cycle progression or mouse infection by this parasite. Two proteins, UBC2 and UEV1, were selected for further study based on their importance in the promastigote to amastigote transition. We demonstrate that UBC2 and UEV1 form a heterodimer capable of carrying out ubiquitination and that the structural basis for this activity is conserved between Leishmania, Saccharomyces cerevisiae and humans. We also show that the interaction of UBC2 with UEV1 alters the nature of the ubiquitination activity performed by UBC2. Overall, we demonstrate the important role that ubiquitination enzymes play in the life cycle and infection process of Leishmania and explore the biochemistry underlying UBC2 and UEV1 function.

Post-translational modifications such as ubiquitination are important for orchestrating the cellular transformations that occur as theLeishmaniaparasite differentiates between its main morphological forms, the promastigote and amastigote. 2 E1 ubiquitin-activating (E1), 13 E2 ubiquitin-conjugating (E2), 79 E3 ubiquitin ligase (E3) and 20 deubiquitinating cysteine peptidase (DUB) genes can be identified in theLeishmania mexicanagenome but, currently, little is known about the role of E1, E2 and E3 enzymes in this parasite. Bar-seq analysis of 23 E1, E2 and E3 null mutants generated in promastigotes using CRISPR-Cas9 revealed numerous loss-of-fitness phenotypes in promastigote to amastigote differentiation and mammalian infection. The E2s UBC1/CDC34, UBC2 and UEV1 and the HECT E3 ligase HECT2 are required for the successful transformation from promastigote to amastigote and UBA1b, UBC9, UBC14, HECT7 and HECT11 are required for normal proliferation during mouse infection. Null mutants could not be generated for the E1 UBA1a or the E2s UBC3, UBC7, UBC12 and UBC13, suggesting these genes are essential in promastigotes. X-ray crystal structure analysis of UBC2 and UEV1, orthologues of human UBE2N and UBE2V1/UBE2V2 respectively, reveal a heterodimer with a highly conserved interface, highlighting the importance of stable UBC2-UEV1 interaction in the function of this complex across diverse eukaryotes. Furthermore, recombinantL. mexicanaE1 UBA1a can load ubiquitin onto UBC2, allowing UBC2-UEV1 to form K63-linked di-ubiquitin chainsin vitro. Notably, UBC2 can also cooperatein vitrowith human E3s RNF8 and BIRC2 to form non-K63-linked polyubiquitin chains, showing that UBC2 can facilitate ubiquitination independent of UEV1, but association of UBC2 with UEV1 inhibits this ability. Our study demonstrates the dual essentiality of UBC2 and UEV1 in the differentiation and intracellular survival ofL. mexicanaand shows that the interaction between these two proteins is crucial for regulation of their ubiquitination activity and function.Author summaryThe post-translational modification of proteins is key for allowingLeishmaniaparasites to transition between the different life cycle stages that exist in its insect vector and mammalian host. In particular, components of the ubiquitin system are important for the transformation ofLeishmaniafrom its insect (promastigote) to mammalian (amastigote) stage and normal infection in mice. However, little is known about the role of the enzymes that generate ubiquitin modifications inLeishmania. Here we characterise 28 enzymes of the ubiquitination pathway and show that many are required for life cycle progression or mouse infection by this parasite. Two proteins, UBC2 and UEV1, were selected for further study based on their importance in the promastigote to amastigote transition. We demonstrate that UBC2 and UEV1 form a heterodimer capable of carrying out ubiquitination and that the structural basis for this activity is conserved betweenLeishmania, Saccharomyces cerevisiaeand humans. We also show that the interaction of UBC2 with UEV1 alters the nature of the ubiquitination activity performed by UBC2. Overall, we demonstrate the important role that ubiquitination enzymes play in the life cycle and infection process ofLeishmaniaand explore the biochemistry underlying UBC2 and UEV1 function.