Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Successful management of an aortoesophageal fistula caused by a fish bone – case report and review of literature

We report a case of aortoesophageal fistula (AEF) caused by a fish bone that had a successful outcome. Aortoesophageal fistula is a rare complication of foreign body ingestion from which few patients survive. Over one hundred cases of AEF secondary to foreign body ingestion have been documented but only seven, including our case, have survived over 12 months. Treatment involved stabilising the patient with a Sengstaken-Blakemore tube and insertion of a thoracic aortic endovascular stent-graft. Unfortunately the stent became infected and definitive open surgical repair involved removing the stent, replacing the aorta with a homograft and coverage with a left trapezius flap while under deep hypothermic arrest

Dietary patterns at 6, 15 and 24 months of age are associated with IQ at 8 years of age

Diet supplies the nutrients needed for the development of neural tissues that occurs over the first 2 years of life. Our aim was to examine associations between dietary patterns at 6, 15 and 24 months and intelligence quotient (IQ) scores at 8 years. Participants were enrolled in an observational birth cohort (ALSPAC study, n = 7,097). Dietary data was collected by questionnaire and patterns were extracted at each time using principal component analysis. IQ was measured using the Wechsler Intelligence Scale for Children at 8 years. Associations between dietary patterns and IQ were examined in regression analyses adjusted for potential confounding and by propensity score matching, with data imputation for missing values. At all ages, higher scores on a Discretionary pattern (characterized by biscuits, chocolate, sweets, soda, crisps) were associated with 1–2 point lower IQ. A Breastfeeding pattern at 6 months and Home-made contemporary patterns at 15 and 24 months (herbs, legumes, cheese, raw fruit and vegetables) were associated with 1-to-2 point higher IQ. A Home-made traditional pattern (meat, cooked vegetables, desserts) at 6 months was positively associated with higher IQ scores, but there was no association with similar patterns at 15 or 24 months. Negative associations were found with patterns characterized by Ready-prepared baby foods at 6 and 15 months and positive associations with a Ready-to-eat foods pattern at 24 months. Propensity score analyses were consistent with regression analyses. This study suggests that dietary patterns from 6 to 24 months may have a small but persistent effect on IQ at 8 years.Lisa G. Smithers, Rebecca K. Golley, Murthy N. Mittinty, Laima Brazionis, Kate Northstone, Pauline Emmett, John W. Lync

Refining esophageal cancer staging after neoadjuvant therapy: importance of treatment response

Objective: Accurate staging is vital for esophageal cancer management. The utility of the American Joint Committee on Cancer (AJCC) staging system 6th edition for esophageal cancer has been questioned for resected patients who receive neoadjuvant chemoradiotherapy (CRT). This study was undertaken to assess the AJCC staging system for patients with esophageal cancer that have received neoadjuvant CRT and to identify clinicopathological variables that predict survival

The identification of 100 ecological questions of high policy relevance in the UK

1. Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2. During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3. The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4. The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5. Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. © 2006 The Authors