Citations

Abstract Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112 ± 4 ng/106 cells, and ECP, 163 ± 2 ng/106 cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.

Background: Reverse total shoulder arthroplasty (RTSA) performed in the setting of massive proximal humeral bone loss often requires special reconstructive techniques. Restoration of the proximal part of the humerus with an allograft provides a number of theoretical benefits, including implant support, restoration of humeral length, deltoid tensioning, and an opportunity to repair the posterior aspect of the cuff to improve strength in external rotation and repair of the subscapularis to improve stability. However, reverse allograft-prosthesis composites (APCs) are costly, are technically demanding to use, and can be compromised by progressive allograft resorption. Methods: Between 2005 and 2012, the lead author used an APC reconstruction in 8 primary and 18 revision RTSAs (26 patients; mean age, 62 years; mean body mass index, 27.9 kg/m 2 ). The indications for the primary RTSAs included severe proximal humeral bone loss after trauma (n = 5) and tumor resection (n = 3). The indications in the revision setting were failed hemiarthroplasty (n = 11), anatomic total shoulder arthroplasty (n = 4), and reverse arthroplasty (n = 3). The most common reason for revision was instability (n = 10). A compression plate was used for graft-to-host fixation in all shoulders. Shoulders were assessed for pain, motion, American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test (SST) score, Neer score, revision or reoperation, radiographic evidence of graft union or resorption, and implant fixation. The mean duration of follow-up was 4 years (range, 2 to 10 years). Results: RTSA using an APC construct resulted in substantial improvements in pain scores (p < 0.0001), elevation (p < 0.0001), and external rotation (p = 0.004). With the numbers available, there were no significant differences in clinical outcomes between primary and revision cases. No patients required revision surgery for nonunion at the host-allograft junction. The mean time to union was 7 months, with 1 patient requiring bone-grafting for delayed union. Other complications included dislocation, deep infection, graft fracture, and periprosthetic fracture distal to the previous APC construct in 1 patient each. The 2 and 5-year revision-free survival rate was 96%. Conclusions: Reconstruction of proximal humeral bone loss with an APC at the time of primary or revision RTSA is safe and effective, with acceptable functional outcomes and complication rates. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Nonvascularized bone grafting (NVBG) and vascularized bone grafts (VBGs) have been used to treat scaphoid nonunions. A comparison of a single institution’ s experience using structural iliac crest bone graft (ICBG), 1,2-intercompartmental supraretinacular artery (1,2-ICSRA), and medial femoral condyle (MFC) grafts to treat scaphoid nonunions was undertaken. Methods: Thirty-one patients underwent ICBG, 33 patients underwent 1,2-ICSRA, and 45 patients underwent MFC grafting. Mean time to follow-up was 16 months (range, 2-153). Twenty-three percent used tobacco products. Mean age was 24 years (range, 11-66), with 86% male patients. Outcomes included union rate, time to healing, range of motion, complications, and reoperations. Results: Union rates and mean time to union were 71% and 19 weeks for the ICBG group, 79% and 26 weeks for the 1,2-ICSRA group, and 89% and 16 weeks for the MFC group, respectively. Failure of union was associated with tobacco use but not with age, gender, time from injury to surgery, or type of fixation. There was no significant difference between the groups regarding range of motion or strength. Conclusions: These findings demonstrate the need for careful patient selection. In patients with the most complicated scaphoid nonunions (avascular necrosis, carpal collapse, and previous surgeries), the MFC group had the highest union rate and fastest time to union. Patients with risk factors for failure should be counseled on the outcomes and possible need for salvage fusion surgery.

Abstract Hepatic steatosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet little is known about the molecular pathology associated with this factor. In this study, we performed a forward genetic screen using Sleeping Beauty (SB) transposon insertional mutagenesis in mice treated to induce hepatic steatosis and compared the results to human HCC data. In humans, we determined that steatosis increased the proportion of female HCC patients, a pattern also reflected in mice. Our genetic screen identified 203 candidate steatosis-associated HCC genes, many of which are altered in human HCC and are members of established HCC-driving signaling pathways. The protein kinase A/cyclic AMP signaling pathway was altered frequently in mouse and human steatosis-associated HCC. We found that activated PKA expression drove steatosis-specific liver tumorigenesis in a mouse model. Another candidate HCC driver, the N-acetyltransferase NAT10, which we found to be overexpressed in human steatosis–associated HCC and associated with decreased survival in human HCC, also drove liver tumorigenesis in a steatotic mouse model. This study identifies genes and pathways promoting HCC that may represent novel targets for prevention and treatment in the context of hepatic steatosis, an area of rapidly growing clinical significance. Cancer Res; 77(23); 6576–88. ©2017 AACR.

The purpose was to determine if smartphone photography is a reliable tool in measuring wrist movement. Smartphones were used to take digital photos of both wrists in 32 normal participants (64 wrists) at extremes of wrist motion. The smartphone measurements were compared with clinical goniometry measurements. There was a very high correlation between the clinical goniometry and smartphone measurements, as the concordance coefficients were high for radial deviation, ulnar deviation, wrist extension and wrist flexion. The Pearson coefficients also demonstrated the high precision of the smartphone measurements. The Bland–Altman plots demonstrated 29–31 of 32 smartphone measurements were within the 95% confidence interval of the clinical measurements for all positions of the wrists. There was high reliability between the photography taken by the volunteer and researcher, as well as high inter-observer reliability. Smartphone digital photography is a reliable and accurate tool for measuring wrist range of motion. Level of evidence: II

VA Cooperative Studies Program #571 (DIVA) was designed to evaluate the efficacy of drug‐eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure when compared with bare‐metal stents (BMS) in participants undergoing stenting of de novo SVG lesions. Participants undergoing clinically indicated stenting of de novo SVG lesions were randomized in a 1:1 ratio to DES or BMS. Randomization was stratified by presence/absence of diabetes mellitus and the number of target SVG lesions (1 vs ≥2) within each participating site. At sites that did not routinely administer 12‐months of dual antiplatelet therapy after SVG stenting participants without acute coronary syndromes received 1 month of open‐label clopidogrel, followed by 11 months of clopidogrel for those assigned to DES and 11 months of placebo for those assigned to BMS. The primary endpoint was the 12‐month incidence of target‐vessel failure (defined as the composite of cardiac death, target‐vessel myocardial infarction, or target‐vessel revascularization). Secondary endpoints included the incidence of other clinical endpoints and the incremental cost‐effectiveness of DES relative to BMS. Due to lower‐than‐anticipated target‐vessel failure rates, target enrollment was increased from 519 to 762. The study had randomized 599 participants when recruitment ended in December 2015. The DIVA trial will provide clarity on the appropriate stent type for de novo SVG lesions.