Citations

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Background: The Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor ( IL6R ) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R -Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection. Methods: Using data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R -Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death. Results: After adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13–0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was −0.06 mm per year (−0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival ( P <0.05). Conclusions: Our proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.

Abstract Background Trends in the distribution of ribotypes for C. difficile associated diarrheal isolates obtained over time in the United States are lacking. As part of surveillance program for C. difficile susceptibility, we analyzed stool isolates for ribotype distribution from a phase 2 trial of surotomycin (2010–2011) (North America sites) as well as a national surveillance study from 2011–2014. Isolates for the surveillance study were referred from 6 geographically distinct medical centers. Methods C. difficile isolates or C. difficile toxin + stools from patients with C. difficile associated diarrhea (CDAD) were submitted for testing to Tufts Medical Center. Following isolation and confirmation as C. difficile, a random sample of isolates were ribotyped by PCR capillary gel electrophoresis. Results 673 isolates over the 5 years of the analysis have been ribotyped to date. There were 49 unique ribotype designations, and 16 ribotypes had more than 10 isolates. The ribotype distribution by year is shown in the table. Conclusion There has been a change in the frequency of ribotypes over time in the US. Of the most common ribotypes seen, 027 has decreased by over 50% while there has been an increase of 014-020, 002, and 106. 014-020 is now the most common ribotype seen in the US. These data suggest that there is a changing epidemiology of C. difficile in the US and continuous monitoring of the ribotype distributions and clinical implications is warranted. Disclosures D. R. Snydman, Merck: Consultant and Grant Investigator, Consulting fee and Research grant; Shire: Consultant, Consulting fee; Summit PLC: Consultant and Grant Investigator, Consulting fee and Research grant; BioK+: Consultant, Consulting fee; Actelion: Grant Investigator, Research grant; S. G. Jenkins, Cormedix: Consultant, Consulting fee; Bayer: Consultant, Consulting fee; Merck: Grant Investigator and Scientific Advisor, Research grant; E. J. C. Goldstein, Merck: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee and Grant recipient; Cubist: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee; Actelion: Grant Investigator, Grant recipient; Summit PLC: Grant Investigator and Scientific Advisor, Grant recipient; R. Patel, Curetis: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee and Research grant; Pocared: Grant Investigator, Research grant; nanoMR: Grant Investigator, Research grant; BioFire: Grant Investigator, Research grant; Check-Points: Grant Investigator, Research grant; 3M: Grant Investigator, Research grant; Cubist: Grant Investigator, Research grant; Merck: Grant Investigator, Research grant; S. Johnson, Bio-K+: Consultant, Consulting fee; D. N. Gerding, Merck, Shire, Cubist, Rebiotix, sanofi pasteur, Summit, DaVoltera, Actelion: Consultant, Consulting fee; CDC, US Dept of Veterans Affairs Research Service: Grant Investigator, Research grant

ABSTRACT In 2011 a surveillance study for the susceptibility to fidaxomicin and epidemiology of Clostridium difficile isolates in the United States was undertaken in seven geographically dispersed medical centers. This report encompasses baseline surveillance in 2011 and 2012 on 925 isolates. A convenience sample of C. difficile isolates or toxin positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution (CLSI M11-A8). Clinical and Laboratory Standards Institute (CLSI), Food and Drug Administration, or European Union of Clinical Antimicrobial Susceptibility Testing (EUCAST) breakpoints were applied where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of 322 strains, stratified by institution, underwent restriction endonuclease analysis (REA). The fidaxomicin MIC 90 was 0.5 μg/ml for all isolates regardless of REA type or toxin gene profile, and all isolates were inhibited at ≤1.0 μg/ml. By REA typing, BI strains represented 25.5% of the isolates. The toxin gene profile of tcdA , tcdB , and cdtA/B positive with a tcdC 18-bp deletion correlated with BI REA group. Moxifloxacin and clindamycin resistance was increased among either BI or binary toxin-positive isolates. Metronidazole and vancomycin showed reduced susceptibility (EUCAST criteria) in these isolates. Geographic variations in susceptibility, REA group and binary toxin gene presence were observed. Fidaxomicin activity against C. difficile isolated in a national surveillance study did not change more than 1 year after licensure. This analysis provides baseline results for future comparisons.