Citations

Development of late-onset respiratory diseases is associated with elevated 8-isoprostane, a marker of oxidative stress, in the airways. However, sex differences exist in development of these diseases. Using an exhaustive exercise bout as a physiological stressor may elucidate whether there is a sex difference with aging in pre- to postexercise airway 8-isoprostane generation. The purpose of this study was to determine whether older women exhibit a greater airway 8-isoprostane response to exhaustive exercise compared with older men and younger controls. Thirty-six individuals completed the study (12 postmenopausal older women (OW) and 12 age-matched older men (OM), 65 ± 4 years of age; and 12 younger controls (YC), 21 ± 2 years of age). Baseline measurements included exhaled breath condensate (EBC) for assessment of airway 8-isoprostane and standard pulmonary function tests (PFTs) to assess forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow at 25%–75% of FVC. Subjects then performed a peak oxygen uptake test to exhaustion on a cycle ergometer. Immediately postexercise, PFTs and EBC were performed. The generation of airway 8-isoprostane from pre- to postexercise was greater in OW compared with OM and YC (p < 0.01), increasing ∼74% ± 77% in OW, while decreasing in OM (∼12% ± 50%) and YC (∼20.9% ± 30%). The OW exhibited a greater airway 8-isoprostane response to exhaustive exercise compared with OM and YC, which may suggest that sex differences in oxidative stress generation following exhaustive exercise may provide a mechanistic rationale for sex differences in late-onset respiratory diseases.

ABSTRACT There is a clinical need to identify new molecular targets for the treatment of osteoporosis, particularly those that simultaneously inhibit bone resorption while stimulating bone formation. We have previously shown in overexpression studies that retinoic acid receptor-related orphan receptor β (Rorβ) suppresses in vitro osteoblast differentiation. In addition, the expression of Rorβ is markedly increased in bone marrow–derived mesenchymal stromal cells with aging in both mice and humans. Here we establish a critical role for Rorβ in regulating bone metabolism using a combination of in vitro and in vivo studies. We used Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing to demonstrate that loss of Rorβ in osteoblasts enhances Wnt signaling, specifically through increased recruitment of β-catenin to T-cell factor/lymphoid enhancer factor (Tcf/Lef) DNA binding sites in the promoters of the Wnt target genes Tcf7 and Opg. This resulted in increased osteogenic gene expression and suppressed osteoclast formation through increased osteoprotegerin (OPG) secretion in Rorβ-deficient cells. Consistent with our in vitro data, genetic deletion of Rorβ in both female and male mice resulted in preserved bone mass and microarchitecture with advancing age due to increased bone formation with a concomitant decrease in resorption. The improved skeletal phenotype in the Rorβ–/– mice was also associated with increased bone protein levels of TCF7 and OPG. These data demonstrate that loss of Rorβ has beneficial skeletal effects by increasing bone formation and decreasing bone resorption, at least in part through β-catenin–dependent activation of the Wnt pathway. Thus, inhibition of Rorβ represents a novel approach to potentially prevent or reverse osteoporosis. © 2017 American Society for Bone and Mineral Research.

PurposeTo implement a reduced field of view (rFOV) technique for cardiac MR elastography (MRE) and to demonstrate the improvement in image quality of both magnitude images and post‐processed MRE stiffness maps compared to the conventional full field of view (full‐FOV) acquisition.MethodsWith Institutional Review Board approval, 17 healthy volunteers underwent both full‐FOV and rFOV cardiac MRE scans using 140‐Hz vibrations. Two cardiac radiologists blindly compared the magnitude images and stiffness maps and graded the images based on several image quality attributes using a 5‐point ordinal scale. Fisher's combined probability test was performed to assess the overall evaluation. The octahedral shear strain‐based signal‐to‐noise ratio (OSS‐SNR) and median stiffness over the left ventricular myocardium were also compared.ResultsOne volunteer was excluded because of an inconsistent imaging resolution during the exam. In the remaining 16 volunteers (9 males, 7 females), the rFOV scans outperformed the full‐FOV scans in terms of subjective image quality and ghosting artifacts in the magnitude images and stiffness maps, as well as the overall preference. The quantitative measurements showed that rFOV had significantly higher OSS‐SNR (median: 1.4 [95% confidence interval (CI): 1.2–1.5] vs. 2.1 [95% CI: 1.8–2.4]), P < 0.05) compared to full‐FOV. Although no significant change was found in the median myocardial stiffness between the 2 scans, we observed a decrease in the stiffness variation within the myocardium from 2.1 kPa (95% CI: [1.9, 2.3]) to 1.9 kPa (95% CI: [1.7, 2.0]) for full‐FOV and rFOV, respectively (P < 0.05) in a subgroup of 7 subjects with ghosting present in the myocardium.ConclusionThis pilot volunteer study demonstrated that rFOV cardiac MRE has the capability to reduce ghosting and to improve image quality in both MRE magnitude images and stiffness maps. Magn Reson Med 80:231–238, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

PurposeTo investigate the feasibility of using artificial neural networks to estimate stiffness from MR elastography (MRE) data.MethodsArtificial neural networks were fit using model‐based training patterns to estimate stiffness from images of displacement using a patch size of ∼1 cm in each dimension. These neural network inversions (NNIs) were then evaluated in a set of simulation experiments designed to investigate the effects of wave interference and noise on NNI accuracy. NNI was also tested in vivo, comparing NNI results against currently used methods.ResultsIn 4 simulation experiments, NNI performed as well or better than direct inversion (DI) for predicting the known stiffness of the data. Summary NNI results were also shown to be significantly correlated with DI results in the liver (R2 = 0.974) and in the brain (R2 = 0.915), and also correlated with established biological effects including fibrosis stage in the liver and age in the brain. Finally, repeatability error was lower in the brain using NNI compared to DI, and voxel‐wise modeling using NNI stiffness maps detected larger effects than using DI maps with similar levels of smoothing.ConclusionArtificial neural networks represent a new approach to inversion of MRE data. Summary results from NNI and DI are highly correlated and both are capable of detecting biologically relevant signals. Preliminary evidence suggests that NNI stiffness estimates may be more resistant to noise than an algebraic DI approach. Taken together, these results merit future investigation into NNIs to improve the estimation of stiffness in small regions. Magn Reson Med 80:351–360, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Objectives: Low serum albumin levels (hypoalbuminemia) have classically been used to identify malnutrition. The effect of increasing severity of malnutrition on postoperative outcomes in patients undergoing hip fracture surgery has not been well delineated on a large scale. Design: Retrospective. Setting: Multicenter. Patient/Participants: A total of 12,373 patients undergoing hip fracture surgery from 2006 to 2013 National Surgery Quality Improvement Project data were identified. Intervention: Patient demographic, comorbidity, and preoperative laboratory data and complication, reoperation, and readmission data were collected. Main Outcome Measurements: Multivariate logistic regression was used to determine the effect of increasing severity of malnutrition on rates of 30-day postoperative complications, readmissions, and reoperations. Results: A total of 12,373 hip fractures met inclusion criteria. A total of 6506 (52.6%) patients had normal albumin levels (albumin ≥3.5 g/dL), 3205 (25.9%) patients were mildly malnourished (albumin 3.1–3.49 g/dL), 2265 (18.3%) were moderately malnourished (albumin 2.4–3.1 g/dL), and 397 (3.2%) patients were severely malnourished (albumin <2.4 g/dL). Mean age was similar between the 4 cohorts (P < 0.001). Severe malnutrition was associated with a 2-fold increase in the odds of postoperative complications and mortality when compared with mild malnutrition (P < 0.001). Increasing severity of malnutrition was associated with significantly longer lengths of stay and higher odds of experiencing a related readmission (P < 0.001). Conclusions: Increasing severity of hypoalbuminemia is independently associated with poorer outcomes in the 30 days after hip fracture surgery. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Purpose To perform a systematic review to determine if there is (1) an association between decreased hip internal rotation and anterior cruciate ligament (ACL) tear rates; (2) an association between radiographic femoroacetabular impingement (FAI) and ACL tear rates; and (3) biomechanical evidence demonstrating increased strain in the ACL of patients with decreased hip internal rotation. Methods A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Studies investigating relationships between hip motion, hip radiographs, and ACL tear were sought. Studies with Levels of evidence I‐IV were eligible for inclusion. Study methodology/evidence were evaluated using Methodological Index for Non‐Randomized Studies (MINORS), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results Eleven studies were analyzed (2 cadaveric in vitro models, 8 clinical studies measuring hip internal rotation (2 concurrently assessing radiographic FAI), and 1 clinical study assessing radiographic FAI alone). Mean MINORS, STROBE, and GRADE for the studies was 82.4%, 20.9 out of 22, and “low,” respectively. A total of 959 subjects (84.8% male; mean age 23.6 ± 3.8 years) were analyzed. Overall, 378 subjects sustained 427 ACL tears (399 primary ACL ruptures, 28 reruptures). Six of 8 clinical studies identified a significant association between limited rotation (internal rotation [IR; loss greater than 10°‐20°], external rotation [ER], or combined IR + ER [loss greater than 20°]) and ACL tears. Two studies found an association between ACL ruptures and radiographic cam/pincer impingement. Two cadaveric models found a significant association between ACL strain and limited hip internal rotation. Conclusions This systematic review identified a significant association between ACL tear and both limited hip rotation and radiographic FAI. Level of Evidence Level IV, systematic review of Levels II‐IV studies.

Study Design: Retrospective cohort study. Objectives: Epidemiologic studies suggest that the prevalence of moderate to severe obstructive sleep apnea (OSA) is increasing. OSA has been linked to increased rates of postoperative complications following surgery. Large studies, however, regarding surgical outcomes in this patient population, particularly in the spine literature, are limited. Consequently, the purpose of this study was to assess the prevalence of and postoperative risks conferred by OSA in the elective spine population. Methods: Using data from the National Inpatient Sample from 2008 to 2012, an estimated 56 372 (5.1%) patients with OSA undergoing elective cervical and thoracolumbar spine surgery were selected and compared to 1 052 837 patients without OSA undergoing the same procedures. Our primary outcome measures included postoperative complication rates, inpatient mortality, length of stay, and total hospital charges. Results: Patients with OSA were, on average 2.6 years older than those without OSA ( P < .001) and had a higher comorbidity burden. The prevalence of OSA increased between 2008 and 2012 from 3.5% to 6.8%; P < .001. OSA was associated with a 3-fold increase in major complications ( P < .001) and was confirmed as an independent risk factor for major complications based on multivariate analysis (odds ratio [OR] = 2.82; 95% CI = 2.59-2.79; P < .001). Rates of deep venous thrombosis were doubled in patients with OSA. OSA was determined to be an independent predictor of pulmonary complications (OR = 2.69; 95% CI = 2.59-2.79; P < .001). OSA did not increase the risk of postoperative mortality. Conclusions: Patients with OSA often have multiple concomitant comorbidities and consequently are at increased risk of experiencing a more difficult postoperative course following elective spine surgery. Specifically, increased risks of pulmonary complications and deep venous thrombosis should be anticipated.

Abstract Patellar tendon ruptures are rare but potentially devastating injuries. Acute repair after patellar tendon rupture affords the best opportunity for tension‐free restoration of the extensor mechanism. Biological augmentation of primary repair is believed to decrease strain across the repair site and reduce the risk of rerupture. We present a technique for primary patellar tendon repair with bidirectional fixation using transosseous tunnels, suture anchor fixation, and ipsilateral hamstring autograft augmentation in a distal patellar pole socket. Technique Video video See video under supplementary data.

Total artificial hearts (TAH) can be used as a bridge to transplant or, occasionally, as destination therapy for patients with severe biventricular dysfunction. Not infrequently TAHs are placed in patients with severe low flow states, in which the lungs of these patients are unable to adjust rapidly to the “normal” right ventricular output of a TAH. These patients may develop variable degrees of pulmonary edema secondary to stress failure of the pulmonary capillaries requiring increased respiratory support, which can occasionally be fatal. In this “how to do it” article, we describe the technique for a pulmonary arteriovenous extracorporeal membrane oxygenation with TAH to avoid sudden pulmonary overflow and gradually expose the lungs to increasing flow.