An open-label randomized study was undertaken to compare a 2-dose regimen (Months 0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months after the full vaccination course there was a 100% seroprotection rate (anti-HBs > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate with the licensed vaccine. The corresponding geometric mean titres were significantly higher for the novel vaccine compared to the standard vaccine: 15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml, respectively. There was a higher prevalence of local symptoms with the adjuvant vaccine (90% of doses) than with the standard vaccine (48% of doses). However, these symptoms (pain, swelling and redness) were predominantly of mild-to-moderate intensity and resolved rapidly without treatment. A 2-dose regimen of the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard regimen in healthy young adults. It is anticipated that the simplified vaccination schedule may improve compliance and reduce costs.
Colorectal cancers (CRCs) diagnosed relatively soon after a colonoscopy are referred to as interval CRCs. It is not clear whether interval CRCs arise from prevalent lesions missed at colonoscopy or represent specific aggressive biology leading to poor survival.
Using Danish population-based medical registries (2000-2009), we investigated patients with "interval" CRC diagnosed within 1-5 years of a colonoscopy, and compared them with cases with colonoscopy =10 years before diagnosis and to "sporadic" CRCs with no colonoscopy before diagnosis. Multivariate logistic regression was used to explore the association between clinical, demographic, and comorbidity characteristics and interval CRC. We assessed survival using Kaplan-Meier methods and mortality rate ratios (MRRs) using Cox regression, adjusting for covariates including the Charlson Comorbidity Index (CCI 0, 1-2, 3+).
The comparison of the 982 interval CRCs to the 358 patients with CRC =10 years after colonoscopy revealed nearly similar characteristics and mortality. In the comparison with the 35,704 sporadic CRCs, interval cases were slightly older (74 vs. 71 years), more likely to be female (54 vs. 48%), have comorbidities (CCI3+: 28 vs. 15%), have proximal tumors (38 vs. 22%), and tumors with mucinous histology (9.1 vs. 7.0%), but stage was similar (metastatic 23 vs. 24%). In logistic regression analysis, female sex, localized stage at diagnosis, proximal tumor location, and high comorbidity burden were factors independently associated with interval CRC. The 1-year survival was 68% (95% confidence interval (CI): 65%, 71%) in interval and 71% (95% CI: 70%, 71%) in sporadic cases, with an adjusted MRR of 0.92 (95% CI 0.82, 1.0). After 5 years, survival was 41% (95% CI: 37%, 44%) in interval and 43% (95% CI: 42%, 43%) in sporadic cases, and the adjusted 2-5 year MRR was 1.0 (95% CI 0.88, 1.2).
Clinical characteristics and survival among interval CRCs did not suggest aggressive biology, but rather that the majority represented missed lesions.
Comment In: Am J Gastroenterol. 2013 Aug;108(8):1341-323912407
Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy.
We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation.
Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within
Cites: Am J Gastroenterol. 2012 Sep;107(9):1315-29; quiz 1314, 133022710576
Cites: Am J Clin Pathol. 2014 Apr;141(4):559-7224619758
Rhododendron ferrugineum L. is a widespread dwarf shrub species growing in high-elevation, alpine environments of the Western European Alps. For this reason, analysis of its growth rings offers unique opportunities to push current dendrochronological networks into extreme environments and way beyond the treeline. Given that different species of the same genus have been successfully used in tree-ring investigations, notably in the Himalayas where Rhododendron spp. has proven to be a reliable climate proxy, this study aims at (i) evaluating the dendroclimatological potential of R. ferrugineum and at (ii) determining the major limiting climate factor driving its growth. To this end, 154 cross-sections from 36 R. ferrugineum individuals have been sampled above local treelines and at elevations from 1800 to 2100masl on northwest-facing slopes of the Taillefer massif (French Alps). We illustrate a 195-year-long standard chronology based on growth-ring records from 24 R. ferrugineum individuals, and document that the series is well-replicated for almost one century (1920-2015) with an Expressed Population Signal (EPS) >0.85. Analyses using partial and moving 3-months correlation functions further highlight that growth of R. ferrugineum is governed by temperatures during the growing season (May-July), with increasingly higher air temperatures favoring wider rings, a phenomenon which is well known from dwarf shrubs growing in circum-arctic tundra ecosystems. Similarly, the negative effect of January-February precipitation on radial growth of R. ferrugineum, already observed in the Alps on juniper shrubs, is interpreted as a result of shortened growing seasons following snowy winters. We conclude that the strong and unequivocal signals recorded in the fairly long R. ferrugineum chronologies can indeed be used for climate-growth studies as well as for the reconstruction of climatic fluctuations in Alpine regions beyond the upper limits of present-day forests.