Second primary squamous cell carcinoma arising in cutaneous flap reconstructions of two head and neck cancer patients

Early complications of myocutaneous flap transfers following surgical eradication of head and neck tumors have been extensively described. However, knowledge concerning long-term complications of these techniques remains limited. We report the cases of two patients with a prior history of squamous cell carcinoma of the head and neck (HNSCC), who developed a second primary SCC on the cutaneous surface of their flaps, years after reconstruction. Interestingly, it seems that the well-known risk of a second primary SCC in patients with previous head and neck carcinoma also applies to foreign tissues implanted within the area at risk. Given the important expansion of these interventions, this type of complication may become more frequent in the future. Therefore, long-term follow-up of patients previously treated for HNSCC not only requires careful evaluation of the normal mucosa of the upper aero-digestive tract, but also of the cutaneous surface of the flap used for reconstruction

Study Protocol. ECSSIT – Elective Caesarean Section Syntocinon® Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon®) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section

<p>Abstract</p> <p>Background</p> <p>Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death.</p> <p>The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4–10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion.</p> <p>Methods and design</p> <p>A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha.</p> <p>Discussion</p> <p>It is both important and timely that we evaluate the optimal approach to the management of the third stage at elective caesarean section. Safe operative delivery is now a priority and a reality for many pregnant women. Obstetricians, obstetric anaesthetists, midwives and pregnant women need high quality evidence on which to base management approaches. The overall aim is to reduce maternal haemorrhagic morbidity and its attendant risks at elective caesarean section.</p> <p>Trial registration</p> <p>number: ISRCTN17813715</p

Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla

Immunopotentiation of Trivalent Influenza Vaccine When Given with VAX102, a Recombinant Influenza M2e Vaccine Fused to the TLR5 Ligand Flagellin

BACKGROUND: Currently controversy exists about the immunogenicity of seasonal trivalent influenza vaccine in certain populations, especially the elderly. STF2.4×M2e (VAX102) is a recombinant fusion protein that links four copies of the ectodomain of influenza virus matrix protein 2 (M2e) antigen to Salmonella typhimurium flagellin, a TLR5 ligand. The objectives of this study were to assess the feasibility of giving VAX102 and TIV in combination in an effort to achieve greater immunogenicity and to provide cross-protection. METHODOLOGY/PRINCIPAL FINDINGS: Eighty healthy subjects, 18-49 years old, were enrolled in May and June 2009 in a double-blind, randomized, controlled trial at two clinical sites. Subjects were randomized to receive either TIV + VAX102 or TIV + placebo. Both arms tolerated the vaccines. Pain at the injection site was more severe with TIV + VAX102. Two weeks after immunization the HAI responses to the H1 and H3 antigens of TIV were higher in those that received TIV + VAX102 than in TIV + placebo (309 vs 200 and 269 vs 185, respectively), although statistically non-significant. There was no difference in the HAI of the B antigen. In the TIV + VAX102 arm, the geometric mean M2e antibody concentration was 0.5 µg/ml and 73% seroconverted. CONCLUSIONS/SIGNIFICANCE: The combination of TIV + VAX102 has the potential to increase the immune response to the influenza A components of TIV and to provide M2e immunity which may protect against influenza A strains not contained in seasonal TIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT00921973

Web Queries as a Source for Syndromic Surveillance

In the field of syndromic surveillance, various sources are exploited for outbreak detection, monitoring and prediction. This paper describes a study on queries submitted to a medical web site, with influenza as a case study. The hypothesis of the work was that queries on influenza and influenza-like illness would provide a basis for the estimation of the timing of the peak and the intensity of the yearly influenza outbreaks that would be as good as the existing laboratory and sentinel surveillance. We calculated the occurrence of various queries related to influenza from search logs submitted to a Swedish medical web site for two influenza seasons. These figures were subsequently used to generate two models, one to estimate the number of laboratory verified influenza cases and one to estimate the proportion of patients with influenza-like illness reported by selected General Practitioners in Sweden. We applied an approach designed for highly correlated data, partial least squares regression. In our work, we found that certain web queries on influenza follow the same pattern as that obtained by the two other surveillance systems for influenza epidemics, and that they have equal power for the estimation of the influenza burden in society. Web queries give a unique access to ill individuals who are not (yet) seeking care. This paper shows the potential of web queries as an accurate, cheap and labour extensive source for syndromic surveillance

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy