Relieving veterinarians' workloads and stress: leveraging Australia's veterinary technologists and nurses.

Like the rest of the world, Australia is in the throes of a dire shortage of veterinarians, while the demand for veterinary professional services grows. This combination has a very real impact on veterinarians' workload and stress, with significant mental health impacts. Times have changed in our profession and it is time for a change in our practice. We need to look at a different way of managing veterinary workloads and demands and, in particular, better utilise our paraprofessional staff. It is the solution right under our noses embracing our veterinary technologists and nurses.

Exploring the impact of athletic identity on gender role conflict and athlete injury fear avoidance in male English professional academy football players.

Men's academy football can encourage a commitment to the athletic role and masculine norms. When injured, the ability to fulfil an athletic masculine identity is threatened and athletes may experience injury fear-avoidance behaviours as part of a negative injury appraisal. The aim of the study was to explore whether higher athletic identity (AI) was associated with higher gender role conflict and injury-related fear-avoidance. Seventy-two male English academy footballers completed an Athletic Identity Measurement Scale (AIMS), Gender Role Conflict Scale (GRCS), and Athlete Fear Avoidance Questionnaire (AFAQ) based on self-reported historical injuries. Correlational analyses were conducted for all variables, and a one-way ANOVA was used to compare high, moderate, and low AI. AIMS was significantly positively correlated with two GRCS subscales: success, power, and competition (SPC) and restricted affectionate behaviour between men (RAM). AIMS exclusivity also positively correlated with SPC and AIMS negative affectivity positively correlated with GRCS total and RAM. Additionally, the current study showed that high and moderate levels of AI had significantly higher levels of total GRCS than those with low AI. No significant results were found for AIMS, GRCS, and AFAQ. Results suggest that players with higher and more exclusive AI may be susceptible to masculine role conflicts, specifically, SPC and RAM, especially when there is a risk to their athletic role. The current study informs sport and health professionals of the need to monitor AI and masculine conformity in academy-level footballers to minimise gender-role conflict and potential maladaptive rehabilitation responses when their identities are threatened.

GM-CSF Promotes Immune Response and Survival in a Mouse Model of COVID-19.

COVID-19 results in increased expression of inflammatory cytokines, but inflammation-targeting clinical trials have yielded poor to mixed results. Our studies of other disorders with an inflammatory component, including Alzheimer's disease, chemobrain, Down syndrome, normal aging, and West Nile Virus infection, showed that treatment with the 'pro-inflammatory' cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in humans or mouse models alleviated clinical, behavioral, and pathological features. We proposed that human recombinant GM-CSF (sargramostim) be repurposed to promote both the innate and adaptive immune responses in COVID-19 to reduce viral load and mortality1. Here, we report the results of a placebo-controlled study of GM-CSF in human ACE2 transgenic mice inoculated intranasally with SARS-CoV2 virus, a model of COVID-19. Infection resulted in high viral titers in lungs and brains and over 85% mortality. GM-CSF treatment beginning one day after infection increased anti-viral antibody titers, lowered mean lung viral titers proportionately (p=0.0020) and increased the odds of long-term survival by up to 5.8-fold (p=0.0358), compared to placebo. These findings suggest that, as an activator of both the innate and adaptive immune systems, GM-CSF/sargramostim may be an effective COVID-19 therapy with the potential to protect from re-infection more effectively than treatment with antiviral drugs or monoclonal antibodies.

Long-Term Follow-up of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Children and Young Adults with Metastatic or Relapsed Ewing Sarcoma: A Single-Institution Experience.

Forty-seven patients with metastatic disease at diagnosis or recurrent Ewing sarcoma (EWS) received high-dose chemotherapy (HDC) followed by tandem (n = 20, from February 13, 1997, to October 24, 2002) or single (n = 27, from October 1, 2004, to September 5, 2018) autologous hematopoietic stem cell transplantation (ASCT). To our knowledge, this is the largest single-institution study with sustained long-term follow-up exceeding 10 years. All patients who underwent single ASCT received a novel conditioning regimen with busulfan, melphalan, and topotecan. The overall survival (OS) and disease-free survival (DFS) were 46% and 37% at 10 years and 42% and 37% at 15 years, respectively. Disease status at transplant and the time to disease relapse prior to ASCT were identified as important prognostic factors in OS, DFS, and risk of relapse. At 10 years, patients who underwent transplantation in first complete response (1CR) had an excellent outcome (OS 78%), patients in 1CR/second complete response (2CR)/first partial response (1PR) had an OS of 66%, and patients at third or more complete response, second or more partial response, or advanced disease had an OS of 26%. Ten-year OS for patients without a history of relapse, with late relapse (≥2 years from diagnosis), or with early relapse (<2 years from diagnosis) was 75%, 50%, and 18%, respectively. Selected patients in 1CR, 2CR, 1PR, and with late relapse had excellent, sustained 10- and 15-year OS and DFS.

Production of embryos and a live offspring using post mortem reproductive material from bison (Bison bison bison) originating in Yellowstone National Park, USA.

Bison from Yellowstone National Park (YNP) have an important genetic history. As one of the few wild herds of bison with no evidence of cattle DNA introgression and a large enough population to maintain genetic diversity, they are considered a conservation priority for the species. Unfortunately, there is a high prevalence of the zoonotic disease brucellosis in the herd. Part of the management strategy for controlling the disease and herd size in YNP is to remove bison from the population during the winter migration out of the park. This interagency management cull provides an opportunity to collect a large number of oocytes from a wild bison population for genetic banking and research purposes. During the winters of 2014-2018, which is the nonbreeding season for bison, oocytes were collected post mortem and used to determine the effects of donor reproductive maturity and pregnancy status on oocyte quality and in vitro fertilization (IVF) outcomes, and to demonstrate the feasibility of producing healthy offspring. Cumulus oocyte complexes (COCs) were placed into an in vitro embryo production (IVP) system, and on days 7, 7.5, and 8 of in vitro culture (Day 0 = day of in vitro fertilization) embryos were assessed for developmental stage and quality prior to vitrification. Embryos were then stored in liquid nitrogen until the breeding season when a subset were warmed, cultured for 6 h, evaluated for survival, and transferred to healthy bison recipients. There were no significant differences in the ability of recovered COCs to support blastocyst development based on female reproductive maturity or pregnancy status (juvenile 79/959 (8.2%) vs sexually mature 547/6544 (8.4%); non-pregnant 188/2302 (8.2%) vs pregnant 556/6122 (9.1%)). Following the transfer of 15 embryos to 10 recipients, one healthy female calf was born. This work demonstrates that live offspring can be generated from COCs collected from YNP bison post mortem in the non-breeding season, and that gamete recovery can be a valuable tool for conservation of valuable genetics for this species while mitigating diseases like brucellosis.

Personalising screening of sight-threatening diabetic retinopathy - qualitative evidence to inform effective implementation.

BACKGROUND: Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals. METHODS: We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semistructured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCP from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24 month) interval risk-based screening. RESULTS: Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWD, referral into screening of PWD with diabetic changes regardless of planned interval. For PWD the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCP and PWD that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWD, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system. CONCLUSIONS: Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.

Sinonasal cancer: an overview of the emerging subtypes.

BACKGROUND: Advances in immunohistochemistry have spearheaded major developments in our understanding and classification of sinonasal tumours. In the last decade, several new distinct histopathological entities of sinonasal cancer have been characterised. OBJECTIVES: This review aims to provide a clinical update of the major emerging subtypes for the ENT surgeon and an overview of the management strategies available for this heterogeneous group of pathologies. CONCLUSION: Although rare, knowledge of sinonasal neoplasm subtypes has implications for prognosis, treatment strategies and the development of novel therapeutic targets.

Self-rated health scores predict mortality among people with type 2 diabetes differently across three different country groupings: findings from the ADVANCE and ADVANCE-ON trials.

AIMS: To explore whether there is a different strength of association between self-rated health and all-cause mortality in people with type 2 diabetes across three country groupings: nine countries grouped together as 'established market economies'; Asia; and Eastern Europe. METHODS: The ADVANCE trial and its post-trial follow-up were used in this study, which included 11 140 people with type 2 diabetes from 20 countries, with a median follow-up of 9.9 years. Self-rated health was reported on a 0-100 visual analogue scale. Cox proportional hazard models were fitted to estimate the relationship between the visual analogue scale score and all-cause mortality, controlling for a range of demographic and clinical risk factors. Interaction terms were used to assess whether the association between the visual analogue scale score and mortality varied across country groupings. RESULTS: The visual analogue scale score had different strengths of association with mortality in the three country groupings. A 10-point increase in visual analogue scale score was associated with a 15% (95% CI 12-18) lower mortality hazard in the established market economies, a 25% (95% CI 21-28) lower hazard in Asia, and an 8% (95% CI 3-13) lower hazard in Eastern Europe. CONCLUSIONS: Self-rated health appears to predict 10-year all-cause mortality for people with type 2 diabetes worldwide, but this relationship varies across groups of countries.

What makes a great clinical team? Stakeholder perspectives on the attributes of effective veterinary health care teams in Australia.

Extensive research in the business and organisational literature links teamwork to enhanced productivity and employee job satisfaction. Good teamwork capability is also a highly regarded graduate attribute linked to employability. This study explored desirable teamwork attributes for veterinary technology graduates in Australia, by surveying veterinarians, veterinary technology graduates, veterinary nurses, clients and academics. Respondents highlighted the importance of seven attributes sourced from the cross-disciplinary teamwork literature-'flexibility' (in approach to work), 'agreeableness', being 'cooperative', 'socially sensitive and perceptive', 'conscientiousness', being 'accepting of others' and 'sharing professional values'. The majority in each stakeholder group viewed all attributes important for teamwork concurring with findings in other fields. Few differences were found between and within groups with veterinarians and academics rating 'conscientiousness' higher than others and female clients placing more importance on relational attributes compared to male clients. Thematic analysis of an open-ended item asking the veterinary health care groups, and veterinary academics, to define teamwork generated nine themes centred on: collaboration, goals and outcomes, sharing values, relationships, diversity, communication, task-orientation, personal attributes, and workplace culture. This study illuminates an interprofessional perspective on veterinary teamwork. Results will be useful for veterinary technology, veterinary nursing and veterinary educators when developing a curriculum for interprofessional teamwork to enhance team performance, employability and, ultimately, the quality of veterinary services.

Characterisation of chitosan molecular weight distribution by multi-detection asymmetric flow-field flow fractionation (AF4) and SEC.

A new method for the molecular weight (MW) determination of chitosans by asymmetric flow field flow fractionation (AF-FFF or AF4) coupled with multi-angle light scattering (MALS) and differential refractive index (RI) detectors is proposed. The method allows the separation of polymer from molecular aggregates typically found in chitosan solutions making possible the accurate determination of MW distribution of the polymer. The effect of different experimental conditions on the obtained results has been evaluated and compared with those obtained from SEC-MALS-RI (size exclusion chromatography-MALS-RI). The chitosans analysed were from different biological sources and of varying degree of acetylation. AF4-MALS-RI results revealed that although aggregates are minimised when using a good solvent, a fraction still remains, and it is only completely eliminated by filtration through small pore sizes (≤0.45µm). This represents a limitation for the characterisation of high MW chitosan, where filtration can lead to considerable sample loss in the filter. The method described here has the advantage of not only allowing the identification and separation of the aggregates present, but also the accurate determination of the MW distribution for a wide range of chitosans of varying type where results are well correlated with those obtained by more conventional techniques.

Quantitative and qualitative assessment of a coding system for reporting CT colonography.

AIM: To validate a coding system implemented to summarise computed tomography colonography (CTC) findings for the detection of suspected colorectal cancer (CRC) by assessing interobserver variability and also to evaluate any weaknesses through qualitative analysis. MATERIALS AND METHODS: All CTC investigations over a 6-month period (01/07/2016 to 31/12/2016) were analysed retrospectively. Each study was read initially by an advanced practitioner radiographer with a final report issued by a consultant gastrointestinal radiologist. Rates of interobserver agreement, using the kappa statistic, provided a quantitative assessment of levels of agreement. Areas of poor interobserver agreement were identified for further qualitative assessment. RESULTS: The present study included 1,321 CTC procedures and the mean age of patients was 68.4 years (range 28-96 years). Percentage agreement for colonic coding was 90% and for extra-colonic coding 47%. This corresponds to kappa scores of 0.69 (substantial agreement) and 0.22 (fair agreement), respectively. Reasons and examples of disagreement in the colonic coding are highlighted. CONCLUSIONS: High interobserver agreement was observed for C coding, suggesting it is a reproducible method of classifying intra-colonic CTC findings. Some of the difference in classifying extra-colonic findings is the perceived importance of incidental findings between readers, as well as differences in skill set; however, some themes recurred in areas of disagreement and recommendations for refining and improving the coding system are provided.

Neighbourhood influence on the fourth dose of diphtheria-tetanus-pertussis vaccination.

OBJECTIVES: Using 542,159 vaccination records from children born between April 1, 2007, and March 31, 2012, in the Michigan Care Improvement Registry and data from the American Community Survey, we determine if neighbourhood-level characteristics at the Census tract level and block level are associated with low uptake of the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP4). STUDY DESIGN: This study was a cross-sectional study. METHODS: We used exploratory factor analysis to determine important socio-economic factors at the Census block level and tract level. We then used generalised estimating equations to test the relationship between block- and tract-level socio-economic factors and DTaP4 uptake. RESULTS: DTaP4 coverage was 88.6% (95% confidence interval [CI]: 88.4%-88.7%) in Michigan. At the Census tract level, two factors surfaced as important for DTaP4 vaccination: 'affluence' (Cronbach's alpha = 0.88) and 'socio-economic disadvantage' (Cronbach's alpha = 0.89). At the Census block level, one factor was important: 'affluence' (Cronbach's alpha = 0.90). Affluence may relate to knowledge about medical exemptions and antivaccination sentiment, while socio-economic disadvantage may indicate limited access to healthcare resources. Children in high-affluence tracts had 1.08% lower vaccination coverage (95% CI: -1.62% to -0.55%) than children in low affluence tracts. Children in low socio-economic disadvantage tracts had 2.92% higher coverage than children in high socio-economic disadvantage tracts (95% CI: 2.58%-3.26%). CONCLUSIONS: This study articulates the need to further understand the contribution of neighbourhood-level characteristics, from both affluent and socioeconomically disadvantaged areas to low vaccination rates. Developing a better understanding of these social environmental factors will help determine useful community-level interventions to improve vaccination rates and reduce disease burden.

Latent variable modeling to develop a robust proxy for sensitive behaviors: application to latrine use behavior and its association with sanitation access in a middle-income country.

BACKGROUND: Globally, diarrhea is a leading cause of child morbidity and mortality. Although latrines are integral for reducing enteric pathogen transmission, several studies have shown no evidence that latrine ownership improved child health. There are a number of explanations for these results. One explanation is that latrine access does not equate to latrine use. Latrine use, however, is difficult to accurately ascertain, as defecation behavior is often stigmatized. To address this measurement issue, we measure latrine use as a latent variable, indicated by a suite of psychosocial variables. METHODS: We administered a survey of 16 defecation-related psychosocial questions to 251 individuals living in rural Ecuador. We applied latent class analysis (LCA) to these data to model the probability of latrine use as a latent variable. To account for uncertainty in predicted latent class membership, we used a pseudo-class approach to impute five different probabilities of latrine use for each respondent. Via regression modeling, we tested the association between household sanitation and each imputed latrine use variable. RESULTS: The optimal model presented strong evidence of two latent classes (entropy = 0.86): consistent users (78%) and inconsistent users (22%), predicted by 5 of our 16 psychosocial variables. There was no evidence of an association between the probability of latrine use, predicted from the LCA, and household access to basic sanitation (OR = 1.1, 95% CI = 0.6-2.1). This suggests that home access to a sanitation facility may not ensure the use of the facility for every family member at all times. CONCLUSION: Effective implementation and evaluation of sanitation programs requires accurate measurement of latrine use. Psychosocial variables, such as norms, perceptions, and attitudes may provide robust proxy-measures. Future longitudinal studies will help to strengthen the use of these surrogate measures, as many of these factors may be subject to secular trends. Additionally, subgroup analyses will elucidate how our  proxy indicators of latrine defecation vary by individual-level characteristics.

Immediate selective laryngeal reinnervation in vagal paraganglioma patients.

OBJECTIVE: This prospective case series aimed to present the outcomes of immediate selective laryngeal reinnervation. METHODS: Two middle-aged women with vagal paraganglioma undergoing an excision operation underwent immediate selective laryngeal reinnervation using the phrenic nerve and ansa cervicalis as the donor nerve. Multidimensional outcome measures were employed pre-operatively, and at 1, 6 and 12 months post-operatively. RESULTS: The voice handicap index-10 score improved from 23 (patient 1) and 18 (patient 2) at 1 month post-operation, to 5 (patient 1) and 1 (patient 2) at 12 months. The Eating Assessment Tool 10 score improved from 20 (patient 1) and 24 (patient 2) at 1 month post-operation, to 3 (patient 1) and 1 (patient 2) at 12 months. There was slight vocal fold abduction observed in patient one and no obvious abduction in patient two. CONCLUSION: Selective reinnervation is safe to perform following vagal paraganglioma excision conducted on the same side. Voice and swallowing improvements were demonstrated, but no significant vocal fold abduction was achieved.

Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro-BNP performance.

AIM: Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants. METHODS: Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development. RESULTS: Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28). CONCLUSION: The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.

Muscle Weakness and Physical Disability in Older Americans: Longitudinal Findings from the U.S. Health and Retirement Study.

IMPORTANCE: Muscle weakness is an important indicator of disability, chronic disease and mortality. While we recently proposed sex/race specific grip strength cutpoints for clinical muscle weakness in a diverse, nationally representative sample of older Americans, the extent to which these cutpoints predict physical disability remains unknown. OBJECTIVE: To examine whether sex/race specific muscle weakness cutpoints predict physical disability status in a nationally representative sample of Americans age 65+. DESIGN: We used data from the 2006-2010 Health and Retirement Study. Fully-adjusted, weighted multinomial logistic regression models were used to quantify the odds of experiencing the onset, progression or persistence of disability in activities of daily living (ADL) among weak versus non-weak individuals over a 2-year period. SETTING: General community, nationally representative sample of older Americans. PARTICIPANTS: Population-based, community dwelling sample of older American adults aged 65-years+; 57 percent were women, 91% were White and the mean age was 75 years. Main Outcome(s) and Measure(s): The primary outcome of interest was disability dynamics, defined by changes in ADL status across at 2- year period. The primary exposure was clinical muscle weakness as defined by previously identified cutpoints. Hypotheses were formulated before analyses were conducted. RESULTS: In this nationally representative sample (n= 8,725), 44% of individuals were classified as weak at baseline. At follow-up, 55% remained independent with no change in their ADL status, 11% had an onset of disability and 4% progressed in their disability status. The odds of experiencing an onset of ADL disability was 54% higher among weak individuals compared those who were not weak at baseline (OR= 1.54, 95% CI= 1.54, 1.5, p<.0001); the odds of experiencing a progression in physical disability status was 2.16 times higher among those who were weak at baseline compared to non-weak individuals (OR= 2.16, 95% CI= 2.15, 2.16, p<.0001). CONCLUSIONS: This is the first study to use grip strength weakness cut-points to identify those who may be at greatest risk for experiencing physical disability in later life. Results underscore the importance of using population-specific cutpoints for clinical weakness in order to identify individuals at greatest risk for adverse health outcomes.

Stable DHLA-PEG capped PbS quantum dots: from synthesis to near-infrared biomedical imaging.

The short shelf-life of water-soluble quantum dots (QDs) due to colloidal instability represents a major drawback to their exploitation. This work examines the colloidal stability of PbS nanoparticles capped with dihydrolipoic acid-polyethylene glycol (DHLA-PEG) ligands terminated with functional groups such as -NH2, -COOH, OMe and -N3. and their application for in vivo imaging. We prove a mechanism of colloidal instability and develop a strategy to produce for the first time stable PEG-capped PbS quantum dots with high quantum yield and optical emission in the first and the second near-infrared (NIR) windows of low absorption of biological tissues. The NIR imaging of in vivo biodistribution is demonstrated at wavelengths >1000 nm, with benefits of reduced tissue absorption and light scattering. The stability, biocompatibility and potential for further QD functionalization open up realistic prospects for non-invasive bioimaging applications.

Acceptability and feasibility of collecting psychosocial data from fathers of very low birth weight infants.

The aim of this study was to determine the feasibility and acceptability of collecting outcome data from parents of very low birth weight (VLBW) infants and to explore the psychological and social adaptation of fathers. Questionnaires were distributed to 38 parents of VLBW infants and 36 parents of term infants within a hospital Neonatal Intensive Care Unit. Field notes were also taken. Parents indicated collecting outcome data in this population was feasible and acceptable, but barriers and difficulties in data collection were identified, particularly for fathers. Furthermore, parents highlighted a lack of emotional support for fathers. In conclusion, research with parents of VLBW infants should happen with consultation, flexibility and measures designed specifically for this population.

Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.

Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly defined high-risk patients who continue to do badly. Novel therapeutic approaches are, therefore, required. A growing number of epigenetic inhibitors are now available including EZH2 inhibitors that are in early-stage clinical trials for treatment of haematological and other cancers with EZH2 mutations or in which overexpression has been correlated with poor outcomes. For the first time, we have identified and validated a robust and independent deleterious effect of high EZH2 expression on outcomes in myeloma patients. Using two chemically distinct small-molecule inhibitors, we demonstrate a reduction in myeloma cell proliferation with EZH2 inhibition, which leads to cell cycle arrest followed by apoptosis. This is mediated via upregulation of cyclin-dependent kinase inhibitors associated with removal of the inhibitory H3K27me3 mark at their gene loci. Our results suggest that EZH2 inhibition may be a potential therapeutic strategy for the treatment of myeloma and should be investigated in clinical studies.

Impact of the method and success of pharyngeal reconstruction on the outcome of treating laryngeal and hypopharyngeal cancers with pharyngolaryngectomy: A national analysis.

BACKGROUND: Surgical treatment of cancers that arise from or invade the hypopharynx presents major reconstructive challenges. Reconstructive failure exposes the airway and neck vessels to digestive contents. METHODS: We performed a national N = near-all analysis of the administrative dataset to identify pharyngolaryngectomies in England between 2002 and 2012. Information about morbidity, pharyngeal closure method and post-operative complications was derived. RESULTS: There were 1589 predominantly male (78%) patients whose mean age at surgery was 62 years. The commonest morbidities were hypertension (24%) and ischemic heart disease (11%). For 232 (15%) patients, pharyngolaryngectomy was performed during an emergency admission. The pharynx was closed primarily in 551 patients, with skin or muscle free or pedicled flaps in 755 patients and with jejunum and gastric pull-up in 123 and 160 patients, respectively. In-hospital mortality rate was 6% and was significantly higher in the gastric pull-up group (11%). Reconstructive failure had an odds ratio of 6.2 [95% confidence interval (CI) 2.4-16.1] for in-hospital death. The five-year survival was 57% and age, morbidities, emergency surgery, gastric pull-up, major acute cardiovascular events, renal failure and reconstructive failure independently worsened prognosis. Patients who underwent pharyngeal reconstruction with radial forearm or anterolateral thigh flaps had lower mortality rates than patients who had jejunum flap reconstruction (hazard ratio = 1.50 [95% CI 1.03-2.19]) or gastric pull-up (hazard ratio = 1.92 [95% CI 1.32-2.80]). CONCLUSIONS: Pharyngolaryngectomy carries a high degree of risk of morbidity and mortality. Reconstructive failure worsens short- and long-term prognosis, and the use of cutaneous free flaps appears to improve survival.