Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.     

12-year survival analysis of 322 Hintegra total ankle arthroplasties from an independent center

Background and purpose — Total ankle arthroplasties (TAAs) have larger revision rates than hip and knee implants. We examined the survival rates of our primary TAAs, and what different factors, including the cause of arthritis, affect the success and/or revision rate.Patients and methods — From 2004 to 2016, 322 primary Hintegra TAAs were implanted: the 2nd generation implant from 2004 until mid-2007 and the 3rd generation from late 2007 to 2016. A Cox proportional hazards model evaluated sex, age, primary diagnosis, and implant generation, pre- and postoperative angles and implant position as risk factors for revision.Results — 60 implants (19%) were revised, the majority (n = 34) due to loosening. The 5-year survival rate (95% CI) was 75% (69–82) and the 10-year survival rate was 68% (60–77). There was a reduced risk of revision, per degree of increased postoperative medial distal tibial angle at 0.84 (0.72–0.98) and preoperative talus angle at 0.95 (0.90–1.00), indicating that varus ankles may have a larger revision rate. Generation of implant, sex, primary diagnosis, and most pre- and postoperative radiological angles did not statistically affect revision risk.Interpretation — Our revision rates are slightly above registry rates and well above those of the developer. Most were revised due to loosening; no difference was demonstrated with the 2 generations of implant used. Learning curve and a low threshold for revision could explain the high revision rate.

Arthritis in the ankle often develops earlier than in the hip or knee, and 70% have a traumatic etiology (Saltzman et al. 2005, Brown et al. 2006). Total ankle arthroplasty (TAA) can be indicated for severe arthritis in the ankle joint, but the anatomical preconditions, like a small surface area and high stress from compression and torque (Bouguecha et al. 2011, Kakkar and Siddique 2011), makes it less durable than hip and knee prosthetics. The Hintegra TAA, a 3-component mobile bearing, uncemented implant (Hintermann et al. 2004) is widely used and results from the development center demonstrate survival rates of 94% and 84% after 5 and 10 years’ follow-up (Barg et al. 2013). This is considerably more than the survival rates from national registries. Labek et al. (2011) demonstrated that development centers report only half of the revision rate that can be found in the few existing national registers. In a systematic review of primary Agility total ankle arthroplasty (DePuy Synthes Orthopedics, Warsaw, IN, USA), the author (Roukis 2012) found that the incidence of complications increased from 7% to 12%, in studies where the inventor was excluded. Similar results were found by Prissel and Roukis (2013), who found an increased incidence of complications from 6% to 13% in studies where the inventor or faculty consultants were excluded. These studies indicated the risk of selection (inventor) and publication (conflict of interest) bias.Planning and surgical technique, including significant experience, are mandatory for a successful outcome. The better result from development centers may reflect, besides the above-mentioned bias, that there is a long learning curve and that the indication for revision surgery varies.We examined the survival rates of primary Hintegra TAAs performed at Hvidovre Hospital, with revision rate as outcome. We report primary diagnosis for primary TAA and examine whether sex, generation of the implant, preoperative angles and implant position affect the revision rate.     

Network Meta-Analysis of Randomized Controlled Trials: Efficacy and Safety of UDCA-Based Therapies in Primary Biliary Cirrhosis

Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.