Research Spotlight

Posted March 15th 2016

Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine.

Manjusha Gaglani M.D.

Manjusha Gaglani, M.D.

Chung, J. R., B. Flannery, M. G. Thompson, M. Gaglani, M. L. Jackson, A. S. Monto, M. P. Nowalk, H. K. Talbot, J. J. Treanor, E. A. Belongia, K. Murthy, L. A. Jackson, J. G. Petrie, R. K. Zimmerman, M. R. Griffin, H. Q. McLean and A. M. Fry (2016). “Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine.” Pediatrics 137(2): 1-10.

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BACKGROUND: Few observational studies have evaluated the relative effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines against medically attended laboratory-confirmed influenza. METHODS: We analyzed US Influenza Vaccine Effectiveness Network data from participants aged 2 to 17 years during 4 seasons (2010-2011 through 2013-2014) to compare relative effectiveness of LAIV and IIV against influenza-associated illness. Vaccine receipt was confirmed via provider/electronic medical records or immunization registry. We calculated the ratio (odds) of influenza-positive to influenza-negative participants among those age-appropriately vaccinated with either LAIV or IIV for the corresponding season. We examined relative effectiveness of LAIV and IIV by using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression. RESULTS: Of 6819 participants aged 2 to 17 years, 2703 were age-appropriately vaccinated with LAIV (n = 637) or IIV (n = 2066). Odds of influenza were similar for LAIV and IIV recipients during 3 seasons (2010-2011 through 2012-2013). In 2013-2014, odds of influenza were significantly higher among LAIV recipients compared with IIV recipients 2 to 8 years old (OR 5.36; 95% CI, 2.37 to 12.13). Participants vaccinated with LAIV or IIV had similar odds of illness associated with influenza A/H3N2 or B. LAIV recipients had greater odds of illness due to influenza A/H1N1pdm09 in 2010-2011 and 2013-2014. CONCLUSIONS: We observed lower effectiveness of LAIV compared with IIV against influenza A/H1N1pdm09 but not A(H3N2) or B among children and adolescents, suggesting poor performance related to the LAIV A/H1N1pdm09 viral construct.

Posted March 15th 2016

Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure.

Sharon DeMorrow Ph.D.

Sharon DeMorrow, Ph.D.

McMillin, M., G. Frampton, M. Quinn, S. Ashfaq, M. de Los Santos, 3rd, S. Grant and S. DeMorrow (2016). “Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure.” Am J Pathol 186(2): 312-323.

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Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1(-/-)) mice were fed a control, cholestyramine-containing, or bile acid-containing diet before azoxymethane (AOM)-induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1(-/-) mice reduced bile acid levels and delayed AOM-induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure.

Posted March 15th 2016

Computer-Assisted Surgical Simulation for Concomitant Temporomandibular Joint Custom-Fitted Total Joint Reconstruction and Orthognathic Surgery.

Larry M. Wolford D.M.D.

Larry M. Wolford, D.M.D.

Wolford, L. M. (2016). “Computer-Assisted Surgical Simulation for Concomitant Temporomandibular Joint Custom-Fitted Total Joint Reconstruction and Orthognathic Surgery.” Atlas Oral Maxillofac Surg Clin North Am 24(1): 55-66.

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Patients with temporomandibular joint (TMJ) conditions and coexisting dentofacial deformities can have these conditions corrected with concomitant TMJ and orthognathic surgery (CTOS) in 1 surgical stage or separated into 2 surgical stages. The 2-stage approach requires the patient to undergo 2 separate operations (surgery to correct the TMJ condition and a second operation to perform the orthognathic surgery) and 2 general anesthetics, significantly lengthening the overall treatment time. Performing CTOS in a single operation significantly decreases treatment time and provides better outcomes but requires careful treatment planning and surgical proficiency in the 2 surgical areas. Some TMJ conditions require total joint prostheses for best results. The application of computer technology for TMJ and orthognathic surgical planning and implementation has significantly improved the accuracy and predictability of treatment outcomes. This article presents the treatment planning and surgical protocol for the application of computer-assisted surgical simulation (CASS) for CTOS cases requiring TMJ reconstruction with patient-fitted total joint prostheses and orthognathic surgery. The CASS protocol decreases the preoperative workup time and increases the accuracy of model preparation and subsequent surgery.

Posted March 15th 2016

Death receptor 6 is a novel plasmacytoid dendritic cell-specific receptor and modulates type I interferon production.

Yong-Jun Liu M.D.

Yong-Jun Liu, M.D.

Li, J., Q. Du, R. Hu, Y. Wang, X. Yin, H. Yu, P. Du, J. Plumas, L. Chaperot, Y. J. Liu and L. Zhang (2016). “Death receptor 6 is a novel plasmacytoid dendritic cell-specific receptor and modulates type I interferon production.” Protein Cell. Feb 24. [Epub ahead of print]

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Plasmacytoid dendritic cells (pDCs) are the professional type I interferon-producing cells of the immune system, which rapidly produce massive amounts of type I interferons (IFN-I) in response to viruses or other nucleic acids ligands through selectively expressed toll-like receptor (TLR)-7 and TLR9. The activation of pDCs not only inhibits virus replication, but also regulates the function of other immune cells and links the innate and adaptive immunity. The local accumulation of pDCs has been reported in both suppressive and overactive immune status (Swiecki and Colonna, 2010), which highlights the importance of characterizing the molecular mechanisms underlying the functional specialization of pDCs in IFN-I production. Death receptor 6 (DR6) is a member of death receptor family, which belongs to the tumor necrosis factor receptor superfamily (TNFRSF). It is reported that DR6 plays vital roles in axon pruning, neuron death, and negatively regulates oligodendrocyte survival, maturation and myelination in neural system. DR6-/- mice exhibit enhanced CD4+ T cell proliferation, Th2 cytokines production and B cell expansion, survival, and humoral responses, which imply that DR6 plays important roles in murine immune responses (Liu et al., 2001; Schmidt et al., 2003). However, the expression profiles and functions of DR6 in human immune system remain largely unknown. We found that DR6 was highly expressed in human pDCs comparing with other blood cells by microarray analysis. Additionally, we found that among the 6 death receptors, including TNFR1, CD95, DR3, DR4, DR5 and DR6, pDCs exclusively expressed DR6 but not others. To confirm the expression of DR6 in pDCs, we performed quantitative real time-PCR analysis on several cell types from peripheral blood. (Excerpt from text.)

Posted March 15th 2016

Atrial Fibrillation Is Associated With Increased Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the Placement of Aortic Transcatheter Valve (PARTNER) Trial.

Michael J. Mack M.D.

Michael J. Mack, M.D.

Biviano, A. B., T. Nazif, J. Dizon, H. Garan, J. Fleitman, D. Hassan, S. Kapadia, V. Babaliaros, K. Xu, R. Parvataneni, J. Rodes-Cabau, W. Y. Szeto, W. F. Fearon, D. Dvir, T. Dewey, M. Williams, M. J. Mack, J. G. Webb, D. C. Miller, C. R. Smith, M. B. Leon and S. Kodali (2016). “Atrial Fibrillation Is Associated With Increased Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the Placement of Aortic Transcatheter Valve (PARTNER) Trial.” Circ Cardiovasc Interv 9(1): e002766.

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BACKGROUND: This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement. METHODS AND RESULTS: Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04). CONCLUSIONS: After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement. CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT00530894.