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Annual vaccination with influenza vaccines is recommended for protection against influenza in the United States. Past clinical studies and meta-analysis, however, have reported conflicting results on the benefits of annual vaccination. B-cell responses elicited following repeat influenza vaccinations over multiple seasons have not been examined in detail. We analyzed the B-cell and antibody (Ab) responses in volunteers vaccinated yearly, from 2010 or 2011 through 2014, with seasonal trivalent inactivated influenza vaccines. Statistical analyses were designed to help correct for possible bias due to reduced sample size in the later years of the study. We show that, after the second annual vaccination, the frequency of vaccine-specific plasmablasts and the binding reactivity of plasmablast-derived polyclonal Abs are reduced and do not increase in subsequent years. Similar trends are observed with the serum hemagglutination inhibition Ab response after each annual vaccination, as well as the binding reactivity of plasmablast-derived polyclonal Abs to the hemagglutinin of influenza A virus vaccine components, even with changes in the seasonal vaccine components during the study. Our findings indicate a diminished B-cell response to annual vaccination with seasonal trivalent influenza vaccine. These results emphasize the need for developing improved strategies to enhance the immunogenicity and efficacy of annual influenza vaccination. [ABSTRACT FROM AUTHOR]

Objective: To identify the frequency of leg amyotrophic diplegia (LAD) at a US academic center, describe the pattern of weakness, and provide comparative data from 8 additional major US academic institutions., Background: LAD is a leg onset variant of progressive muscular atrophy (PMA). LAD weakness is confined to the legs for at least 2 years, and there are no upper motor neuron signs., Design/methods: We present a retrospective chart review of 24 patients with the LAD presentation from the University of Kansas Medical Center ( n = 8 cases) and from 8 US academic institutions (n = 16 cases)., Results: Of the 318 subjects identified in the University of Kansas Medical Center Neuromuscular Research Database, 82% (260 subjects) had amyotrophic lateral sclerosis (ALS), 1.9% (6) had familial ALS, 6.6% (21) had primary lateral sclerosis, and 9.2% (29) had lower motor neuron (LMN) disease. Of these 29 cases, 16 had PMA, 5 had brachial amyotrophic diplegia, while 8 had LAD. The mean LAD age of onset was 58 years with a male/female ratio of 3/1. Onset was asymmetric in 7/8. We identified a pelviperoneal pattern of weakness (sparing of knee extension and/or ankle plantar flexion) in 4 cases and distal predominant weakness in 3 cases. All patients had electrodiagnostic findings consistent with motor neuron disease confined to the lower extremities. We present LAD disease duration and survival data from 8 major academic neuromuscular centers. At last follow-up, weakness progressed to involve the arms in 6/24 LAD cases and of these 6 cases, 2 patients died from progression to typical ALS. From onset of symptoms, mean survival in LAD is 87 months, with 92% of cases being alive., Conclusions/relevance: The natural history of LAD differs from typical forms of ALS and PMA. LAD is a slowly progressive disorder that accounts for a fourth of LMN disease cases. An asymmetric pelviperoneal pattern of weakness should heighten the suspicion for LAD.

Interferon (IFN)-alpha-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-alpha therapy and incubated the cells with or without IFN-alpha for 6 hours, followed by microarray assay to identify IFN-induced gene transcription. The microarray datasets were analyzed statistically according to the patients' race and virological responses to subsequent IFN-alpha treatment. The global induction of IFN-stimulated genes (ISGs) was significantly greater in sustained virological responders compared with nonresponders and in white patients compared with black patients. In addition, a significantly greater global induction of ISGs was observed in sustained virological responders compared with nonresponders within the group of white patients. The level of IFN-induced signal transducer and activator of transcription (STAT) 1 activation, a key component of the Janus kinase (JAK)-STAT signaling pathway, correlated with the global induction of ISGs and was significantly higher in white patients than in black patients. In conclusion, both treatment outcome and race are associated with different transcriptional responses to IFN-alpha. Because this difference is evident in the global induction of ISGs rather than a selective effect on a subset of such genes, key factors affecting the outcome of IFN-alpha therapy are likely to act at the JAK-STAT pathway that controls transcription of downstream ISGs.