Citations

AbstractObjectivesTo summarize the published data of combined transcatheter aortic and mitral valve intervention (CTAMVI).BackgroundCTAMVI, a combination of either transcatheter aortic valve replacement (TAVR) or transcatheter aortic valve‐in‐valve (TAViV) and transcatheter mitral valve replacement (TMVR), transcatheter mitral valve‐in‐valve/valve‐in‐ring (TMViV/ViR), or percutaneous mitral valve repair (PMVR) is an attractive alternative in high‐surgical risk patients with combined aortic and mitral valve disease. However, its procedural details and clinical outcomes have not been well described.MethodsWe performed a systematic review of all the published articles from PUBMED and EMBASE.ResultsA total of 37 studies with 60 patients were included. The indication for CTAMVI was high or inoperable surgical risk and symptomatic severe aortic stenosis (92%) or severe aortic regurgitation (8%) combined with moderate to severe/severe mitral stenosis (30%) or moderate/severe mitral regurgitation (65%) or both (5%). In majority of the cases, aortic valve intervention was performed prior to the mitral valve. Mortality rate were 25% for TAVR + TMVR (range 42 days to 10 months), 17% for TAVR + TMViV/ViR (range 13 days to 6 months), 0% for TAViV + TMViV/ViR (range 6–365 days), and 15% for TAVR/ViV + PMVR (range 17 days to 419 days). Significant (more than moderate) paravalvular regurgitation post‐procedure was rare.ConclusionsCTAMVI appears to confer reasonable clinical outcome. Further large study is warranted to clarify the optimal strategy, procedural details and clinical outcomes in the future.

AbstractBackgroundEvidence suggests that medical service offerings vary by hospital teaching status. However, little is known about how these translate to patient outcomes. We therefore sought to evaluate this gap in knowledge in patients undergoing Transcatheter aortic valve replacement (TAVR) in the United States.MethodsThis study was conducted using the National Inpatient Sample (NIS) in the United States from 2011 to 2014. Teaching status was classified, as teaching vs. nonteaching and endpoints were clinical outcomes, length of stay and cost. Procedure‐related complications were identified via ICD‐9 coding and analysis was performed via mixed effect model.ResultsAn estimated 33,790 TAVR procedures were performed in the U.S between 2011 and 2014, out of which 89.3% were in teaching hospitals. Mean (SD) age was 81.4 (8.5) and 47% were females. There was no significant difference between teaching versus nonteaching hospitals in regards to the primary outcome of in‐hospital mortality and secondary outcomes of several cardiovascular and other end points except for a high rates of acute kidney injury (AKI) (OR: 1.34 [95% CI, 1.04–1.72]) and lower rate for use of mechanical circulatory support devices in teaching vs. nonteaching centers. The mean length of stay was significantly higher in teaching hospitals (7.7 days) vs. nonteaching hospitals (6.8 days) (P = 0.002) and so was the median cost of hospitalization (USD 50,814 vs. USD 48, 787, P = 0.02) for teaching vs. nonteaching centers.ConclusionMost TAVR related short‐term outcomes including all cause in‐hospital mortality are about the same in teaching and nonteaching hospitals. However, AKI, length of hospital stay and TAVR related cost were significantly higher in teaching than nonteaching hospitals. There was more use of mechanical circulatory support in nonteaching than teaching hospitals.

BACKGROUND13‐Cis retinoic acid (13‐CRA) is a synthetic vitamin A derivative. High‐dose 13‐CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long‐term results from a phase 3 randomized trial that compared treatment with low‐dose 13‐CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS).METHODSIn total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low‐dose 13‐CRA (weight‐based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing‐risk approach and the log‐rank test were used to compare the time to SPT and OS, respectively, between groups.RESULTS13‐CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13‐CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13‐CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow‐up of 16 years. The main 13‐CRA related toxicities were dry skin and cheilitis.CONCLUSIONSTreatment with low‐dose 13‐CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653‐4662. © 2017 American Cancer Society.

Objective To determine the prevalence and outcomes of intracranial aneurysm (IA) in patients with bicuspid aortic valve (BAV). Methods Retrospective review of patients with BAV who underwent brain MR angiography at the Mayo Clinic from 1994 to 2013. Results There were 678 patients included in this study—mean age 57±13 years, men 480 (71%), mean follow-up 10±3 years (5913 patient-years). Coarctation of aorta (COA) was present in 154 (23%) patients. There were 59 IAs identified in 52 of 678 patients (7.7%). IA was present in 20/154 patients (12.9%) with COA and 32/524 patients (5.7%) without COA (p<0.001). For the patients without COA, female gender and right–left cusp fusion were risks factors for IA in women after adjustment for all potential variables (HR 1.76, CI 1.31 to 2.68, p=0.03). There was no significant trend in the risk for IA across age tertiles: age ≤40 years versus 41–60 years (HR 1.19, p=0.34), and age 41–60 years versus 61–80 years (HR 1.06, p=0.56). Among the 52 patients with IA, enlargement occurred in three patients (6%), rupture in two patients (4%) and four patients (8%) underwent coil embolisation. For the 626 patients without IA at baseline, no patient developed IA over 7±2 years of imaging follow-up. Conclusions BAV is associated with a higher prevalence of IA compared to the general population, and this risk is higher in patients with COA, right–left cusp fusion and female gender.

Abstract Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells. A lower antiviral resistance in Tfh was consistent with a higher susceptibility to retroviral infections. Mechanistically, we found that BCL6, a master regulator of Tfh cell development, binds to ISG loci and inhibits the expression of MX2 and IFITM3 in Tfh cells. We demonstrate further that inhibition of the BCL6 BR-C, ttk, and bab (BTB) domain function increases the expression of ISGs and suppresses HIV infection and replication in Tfh cells. Our data reveal a regulatory role of BCL6 in inhibiting antiviral resistance factors in Tfh cells, thereby promoting the susceptibility Tfh cells to viral infections. Our results indicate that the modulation of BCL6 function in Tfh cells could be a potential strategy to enhance Tfh cell resistance to retroviral infections and potentially decrease cellular reservoirs of HIV infection.

Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions, such as primary sclerosing cholangitis (PSC), are risk factors. Noninvasive differential diagnosis between intrahepatic CCA and hepatocellular carcinoma (HCC) is sometimes difficult. Accurate noninvasive biomarkers for PSC, CCA, and HCC are not available. In the search for novel biomarkers, serum extracellular vesicles (EV) were isolated from CCA (n = 43), PSC (n = 30), or HCC (n = 29) patients and healthy individuals (control, n = 32); and their protein content was characterized. By using nanoparticle tracking analysis, serum EV concentration was found to be higher in HCC than in all the other groups. Round morphology (by transmission electron microscopy), size (∼180 nm diameter by nanoparticle tracking analysis), and markers (clusters of differentiation 9, 63, and 81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed multiple differentially expressed proteins among groups. Several of these proteins showed high diagnostic values with maximum area under the receiver operating characteristic curve of 0.878 for CCA versus control, 0.905 for CCA stage I‐II versus control, 0.789 for PSC versus control, 0.806 for noncirhottic PSC versus control, 0.796 for CCA versus PSC, 0.956 for CCA stage I‐II versus PSC, 0.904 for HCC versus control, and 0.894 for intrahepatic CCA versus HCC. Proteomic analysis of EV derived from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by normal human cholangiocytes. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release to serum of EV containing some similar human oncogenic proteins. Conclusion : Proteomic signatures found in serum EV of CCA, PSC, and HCC patients show potential usefulness as diagnostic tools. (H epatology 2017;66:1125‐1143).