Citations

Purpose To determine the feasibility of shear wave elastography (SWE) with B‐mode ultrasound in predicting the stiffness of the rotator cuff muscle before arthroscopic rotator cuff repair to evaluate the difficulty of the surgical procedure, as well as to compare SWE with the Goutallier stage on magnetic resonance imaging (MRI). Methods Thirty‐eight patients with a full‐thickness supraspinatus tear requiring arthroscopic rotator cuff repair participated. The Goutallier stage of fatty infiltration on MRI was measured before surgery, as was the SWE modulus of the anterior superficial, anterior deep, posterior superficial, and posterior deep (PD) regions of the supraspinatus muscle. To measure the stiffness of the supraspinatus musculotendinous unit during surgery, the supraspinatus tendon was axially stretched until the anatomic insertion site was reached, and force per deformation was recorded. The correlation between stiffness of the supraspinatus and SWE value in each region of the supraspinatus muscle or Goutallier stage was determined. In addition, patients were divided into 2 groups: (1) In the complete footprint coverage group, greater than 50% of the footprint was covered during the stiffness measurement, and (2) in the incomplete footprint coverage group, less than 50% of the footprint was covered during the stiffness measurement. Differences in SWE value and Goutallier stage were measured between the 2 groups. Results The best correlation of stiffness with the SWE modulus of the PD muscle of the supraspinatus was R = 0.69, and the correlation of stiffness with the Goutallier stage on MRI was R = 0.48. The SWE value of the PD region was greater in the incomplete footprint coverage group than in the complete footprint coverage group, although the Goutallier stage was not significantly different. Conclusions The highest correlation with stiffness of the supraspinatus musculotendinous unit was with the SWE modulus of the PD muscle, as compared with SWE evaluation of the other regions or the Goutallier stage on MRI. Ultrasound SWE can predict the stiffness of the supraspinatus musculotendinous unit best. Clinical Relevance Rotator cuff retraction adds difficulty to arthroscopic rotator cuff repair. Ultrasound SWE may be used for presurgical planning.

Background The purpose of this study is to assess the incidence of acromial stress fractures in a population of reverse shoulder arthroplasties (RSA) and determine potential risk factors for fracture. Patients and Methods Between August 2004 and December 2013, 1082 primary RSA were performed at a single institution. Twelve (1.11%) patients were diagnosed with a postoperative acromial stress fracture. This group was case-matched to a control group of 48 shoulders. Clinical and radiographic risk factors for fracture were assessed. Results Compared to controls, fractures were less satisfied with their outcome despite equivalent American Shoulder and Elbow Surgeons scores, pain scores, and range of motion. Osteoporosis was significantly associated with acromial fractures ( P = .027). A smaller lateral offset of the greater tuberosity, greater arm lengthening, and a thinner acromion were more common in the fracture group ( P = .026, P = .004, and P = .008, respectively). Conclusions In summary, postoperative acromial stress fractures appear to be incidental lesions with little influence on the outcome after RSA. The combination of a thin acromion and superior migration of the humeral head increase the risk of acromial fracture. Lateralized designs that do not excessively verticalize the deltoid line of pull on the acromion may decrease the risk of postoperative acromial fractures.

AbstractIntroductionWe conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J‐ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America.MethodsA total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography‐ or cerebrospinal fluid amyloid β(1–42)‐positive LMCI and mild AD between J‐ADNI and ADNI.ResultsAmyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J‐ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid‐positive LMCI in J‐ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J‐ADNI (n = 73) compared with ADNI (n = 230).DiscussionThese results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries.

Background: Flexor tendon injury is common, and tendon reconstruction is indicated clinically if the primary repair fails or cannot be performed immediately after tendon injury. The purpose of the current study was to compare clinically standard extrasynovial autologous graft (EAG) tendon and intrasynovial allogeneic graft (IAG) that had both undergone biolubricant surface modification in a canine in vivo model. Methods: Twenty-four flexor digitorum profundus (FDP) tendons from the second and fifth digits of 12 dogs were used for this study. In the first phase, a model of failed FDP tendon repair was created. After 6 weeks, the ruptured FDP tendons with a scarred digit were reconstructed with the use of either EAG or IAG tendons treated with carbodiimide-derivatized hyaluronic acid and lubricin. At 12 weeks after tendon reconstruction, the digits were harvested for functional, biomechanical, and histologic evaluations. Results: The tendon failure model was a clinically relevant and reproducible model for tendon reconstruction. The IAG group demonstrated improved digit function with decreased adhesion formation, lower digit work of flexion, and improved graft gliding ability compared with the EAG group. However, the IAG group had decreased healing at the distal tendon-bone junction. Our histologic findings verified the biomechanical evaluations and, further, showed that cellular repopulation of allograft at 12 weeks after reconstruction is still challenging. Conclusions: FDP tendon reconstruction using IAG with surface modification has some beneficial effects for reducing adhesions but demonstrated inferior healing at the distal tendon-bone junction compared with EAG. These mixed results indicate that vitalization and turnover acceleration are crucial to reducing failure of reconstruction with allograft. Clinical Relevance: Flexor tendon reconstruction is a common surgical procedure. However, postoperative adhesion formation may lead to unsatisfactory clinical outcomes. In this study, we developed a potential flexor tendon allograft using chemical and tissue-engineering approaches. This technology could improve function following tendon reconstruction.

Abstract Purpose: ZIP4 is overexpressed in human pancreatic cancer and promotes tumor growth. However, little is known about the role of ZIP4 in advanced stages of this dismal neoplasm. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by ZIP4-modulating pancreatic tumor metastasis. Experimental Design: The expression of ZIP4, ZO-1, claudin-1, and ZEB1 in human pancreatic cancer tissues, genetically engineered mouse model, xenograft tumor model, and pancreatic cancer cell lines were examined, and the correlations between ZIP4 and those markers were also analyzed. Functional analysis of ZO-1, claudin-1, and ZEB1 was investigated in pancreatic cancer cell lines and orthotopic xenografts. Results: Genetic inactivation of ZIP4 inhibited migration and invasion in pancreatic cancer and increased the expression of ZO-1 and claudin-1. Conversely, overexpression of ZIP4 promoted migration and invasion and increased the expression of ZEB1 and downregulation of the aforementioned epithelial genes. ZIP4 downregulation of ZO-1 and claudin-1 requires the transcriptional repressor ZEB1. Further analysis demonstrated that ZIP4-mediated repression of ZO-1 and claudin-1 leads to upregulation of their targets FAK and Paxillin. Silencing of ZIP4 caused reduced phosphorylation of FAK and Paxillin, which was rescued by simultaneous blocking of ZO-1 or claudin-1. Clinically, we demonstrated that ZIP4 positively correlates with the levels of ZEB1 and inversely associates with the expression of ZO-1 and claudin-1. Conclusions: These findings suggest a novel pathway activated by ZIP4-controlling pancreatic cancer invasiveness and metastasis, which could serve as a new therapeutic target for this devastating disease. Clin Cancer Res; 24(13); 3186–96. ©2018 AACR.

Background Ossabaw pigs are unique miniature swine with genetic predisposition to develop metabolic syndrome and coronary atherosclerosis after extended periods receiving atherogenic diets. We have hypothesized that transgenic Ossabaw swine expressing chimp PCSK9 (proprotein convertase subtilisin‐like/kexin type 9) containing the D374Y gain of function would develop familial hypercholesterolemia and coronary artery plaques more rapidly than Landrace swine with the same transgene. Methods and Results Ossabaw and Landrace PCSK9 gain‐of‐function founders were generated by Sleeping Beauty transposition and cloning. Histopathologic findings in the Ossabaw founder animal showed more advanced plaques and higher stenosis than in the Landrace founder, underscoring the Ossabaw genetic predisposition to atherosclerosis. We chose to further characterize the Ossabaw PCSK9 gain‐of‐function animals receiving standard or atherogenic diets in a 6‐month longitudinal study using computed tomography, magnetic resonance (MR) imaging, intravascular ultrasound, and optical coherence tomography, followed by pathological analysis of atherosclerosis focused on the coronary arteries. The Ossabaw model was consistently hypercholesterolemic, with or without dietary challenge, and by 6 months had consistent and diffuse fibrofatty or fibroatheromatous plaques with necrosis, overlying fibrous caps, and calcification in up to 10% of coronary plaques. Conclusions The Ossabaw PCSK9 gain‐of‐function model provides consistent and robust disease development in a time frame that is practical for use in preclinical therapeutic evaluation to drive innovation. Although no animal model perfectly mimics the human condition, this genetic large‐animal model is a novel tool for testing therapeutic interventions in the context of developing and advanced coronary artery disease.

Abstract Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab-KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM-MSC compared to untreated MSC and compared to other organs. KIM-MSC-injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab-KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell-based treatment of ischemic kidney injury.