Plastic physicians: The surgical salamanders of the COVID-19 pandemic.

At the time of writing, coronavirus disease-2019 (COVID-19) has affected 6.42 million people globally and over 380,000 deaths, with the United Kingdom now having the highest death rate in Europe. The plastic surgery department at Leeds Teaching Hospitals put necessary steps in place to maintain an excellent urgent elective and acute service whilst also managing COVID-positive medical patients in the ward. We describe the structures and pathways implemented together with complex decision-making, which has allowed us to respond early and effectively. We hope these lessons will prove a useful tool as we look to open conversations around the recovery of normal activity.

Current role of sentinel lymph node biopsy in the management of cutaneous melanoma: A UK consensus statement.

Sentinel node biopsy (SNB) has been at the forefront of the surgical staging of melanoma patients for the past 15 years. The high accuracy of this prognostic staging procedure is now recognised in all international guidelines for melanoma. However during this period there have been a number of important changes in the management of melanoma, many occurring within the past five years. The outcomes of five recent randomised Phase 3 trials have established the role of adjuvant targeted therapy and immunotherapy in resected Stage 3 and Stage 4 disease and have potentially changed the role of SNB. Two landmark international prospective studies have examined the benefit of performing a completion lymph node dissection (CLND) following the detection of microscopicallyinvolved sentinel nodes. Finally, the marked increase in the incidence of melanoma and the role of SNB in potentially guiding therapy has resulted in a significant increase in the pathological workload of the dermatopathology services. To address these issues a multi-disciplinary consensus meeting involving many melanoma experts from the UK was convened in May 2018. Three main areas were considered: oncology, surgery and pathology. This report is a summary of the conclusions reached, which were agreed by the clinicians attending the meeting and then externally peer reviewed. The recommendations summarised in this Consensus Statement.

Combined clearance of pelvic and superficial nodes for clinical groin melanoma.

30-44% of patients with clinical groin node melanoma have involved pelvic nodes. Clinical guidelines selectively target pelvic lymph node dissection (PLND) to those meeting radiological and clinico-pathological criteria, but we lack satisfactory diagnostic tools to preoperatively identify patients with pelvic node disease. We evaluate routine PLND for all patients undergoing superficial node dissection (SLND), performed as a combined single-stage ilioinguinal lymph node dissection (ILND). Retrospective analysis of 67 ILNDs in consecutive patients presenting with palpable, cytologically melanocytic groin nodes. We examine predictors of pelvic node status and determine efficacy of 2010 UK guidelines in patient selection for PLND. 28 patients (42%) had histologically positive pelvic nodes; half had just one involved node (53.6%). 43% of pelvic metastases were radiologically occult. Significant predictors of pelvic melanoma were stage N3 groin nodes (p = 0.049), one third of groin nodes involved (p = 0.0009), positive Cloquet's node (p = 0.005), previous in transit disease (p = 0.001), and staging CT (p = 0.007). UK guidelines, primarily reliant upon staging CT, were effective selection criteria (p = 0.04), identifying 57% of pelvic metastases. CT and in-transit disease status in combination was the strongest predictor of pelvic disease (p = 0.006, RR 4.5, PPV 0.75, NPV 0.83). A combined CT and in-transit disease status provides a potentially clinically useful preoperative selection tool for ILND. With a high prevalence of occult pelvic node involvement, potential to avoid the morbidity of untreated pelvic nodes, and 5 year survival figures of 24-35% following surgery, we advocate ILND in all patients with clinically evident melanoma in a single groin node.

Measles virus causes immunogenic cell death in human melanoma.

Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host antitumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response.

Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens.

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.

Melanoma sentinel node biopsy and prediction models for relapse and overall survival.

BACKGROUND: To optimise predictive models for sentinal node biopsy (SNB) positivity, relapse and survival, using clinico-pathological characteristics and osteopontin gene expression in primary melanomas. METHODS: A comparison of the clinico-pathological characteristics of SNB positive and negative cases was carried out in 561 melanoma patients. In 199 patients, gene expression in formalin-fixed primary tumours was studied using Illumina's DASL assay. A cross validation approach was used to test prognostic predictive models and receiver operating characteristic curves were produced. RESULTS: Independent predictors of SNB positivity were Breslow thickness, mitotic count and tumour site. Osteopontin expression best predicted SNB positivity (P=2.4 × 10⁻7), remaining significant in multivariable analysis. Osteopontin expression, combined with thickness, mitotic count and site, gave the best area under the curve (AUC) to predict SNB positivity (72.6%). Independent predictors of relapse-free survival were SNB status, thickness, site, ulceration and vessel invasion, whereas only SNB status and thickness predicted overall survival. Using clinico-pathological features (thickness, mitotic count, ulceration, vessel invasion, site, age and sex) gave a better AUC to predict relapse (71.0%) and survival (70.0%) than SNB status alone (57.0, 55.0%). In patients with gene expression data, the SNB status combined with the clinico-pathological features produced the best prediction of relapse (72.7%) and survival (69.0%), which was not increased further with osteopontin expression (72.7, 68.0%). CONCLUSION: Use of these models should be tested in other data sets in order to improve predictive and prognostic data for patients.

Revised UK guidelines for the management of cutaneous melanoma 2010.

These guidelines for the management of cutaneous melanoma present an evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiology, diagnosis, investigation, and follow-up.

Distally based double paddle fasciocutaneous island flap following lower limb trauma.

We report a modification of the distally based islanded fasciocutaneous flap that is suited to cover two separate defects following lower limb trauma.

Australia's university courses: are they meeting the educational expectations of the National Environmental Health Strategy?

Australia has developed a national strategy to encourage an intersectoral approach to environmental health and the creation of an environment that promotes good health and prevents problems. This strategy has implications for the education and training of the workforce. Therefore, the authors conducted a survey of courses in environmental health and other courses highly relevant to the environment offered by Australian universities in 2000. The purpose was to determine the extent to which those courses meet the educational expectations of the National Environmental Health Strategy. Results of the survey showed that Australia's universities are not meeting all the educational expectations of the national strategy. These findings might prompt other countries that agree with the thrust of the strategy to review their own educational offerings.

Critical review of epidemiological studies of the association between smoking and non-Hodgkin's lymphoma.

Smoking has been suggested to increase the risk of non-Hodgkin's lymphoma (NHL) but the results of epidemiological studies have been inconsistent. The aim of this work was to assess whether the findings of individual studies might have arisen by chance, bias or confounding and whether any associations found between smoking and NHL represent cause-and-effect. Reports of the association between smoking and NHL were identified from Medline. Confidence intervals on relative risks and odds ratios, use of multiple comparisons, and information on source, direction, actual existence and size of potential biases and confounding and features of any associations were abstracted. Four out of five cohort studies found no association between current smoking and NHL but three may have been biased against doing so. One found an association with follicular lymphoma but without a convincing exposure-risk gradient. The fifth found a strong association and an exposure-response gradient with ever smoking but excluded living cases from the end-point. Only one study found an association with past smoking which lacked features of causality. Eight out of 14 case-control studies found no association between current and/or past smoking and NHL but five may have been biased against doing so. Of six positive studies, three involved multiple comparisons, the association of one became non-significant after eliminating bias, four did not explore features of causality and one found an association only in heavy smokers, particularly under 45 years old. There are no grounds to reject the null hypothesis but associations should continue to be sought particularly in subgroups of smokers and with NHL subtypes.

Helicobacter pylori infection and fasting plasma glucose concentration.

BACKGROUND: Helicobacter pylori infection raises basal and meal stimulated serum gastrin concentrations and lowers iron stores, which may in turn reduce fasting plasma glucose concentrations in the population. AIM: To determine whether H pylori infection leads to lower fasting plasma glucose concentrations in the population. METHODS: One hundred and seventy three women and 165 men, randomly selected from the electoral rolls of an Australian city, participated in a cardiovascular risk factor survey. Plasma glucose concentrations and H pylori IgG antibody titres were measured. Non-fasting subjects and pregnant women were excluded, as were known diabetics, whose plasma glucose concentrations would be affected by diet and/or medications. Fasting plasma glucose concentrations were logarithmically transformed and the relation with H pylori infection, adjusting for age and other confounding factors, was determined for men and women separately by analyses of variance. RESULTS: Helicobacter pylori infection was significantly associated with fasting plasma glucose concentration among women. Infected women had a lower mean fasting plasma glucose concentration (5.2 mmol/litre; range, 3.9-8.2) than did non-infected women (5.4 mmol/litre; range, 3.9-11.1). CONCLUSIONS: Helicobacter pylori infection may lead to lower fasting plasma glucose concentrations among women and should be considered when interpreting concentrations bordering on diabetes.

Determinants of basal plasma gastrin levels in the general population.

BACKGROUND: There is considerable variation in basal plasma gastrin levels in healthy subjects. Although high plasma gastrin levels may be causally associated with duodenal ulcer and colorectal cancer, there has been little research to identify the factors that determine basal gastrin levels in the general population. METHODS: Helicobacter pylori IgG antibodies and fasting basal gastrin concentrations were measured in 134 males and 137 females who had participated in a cardiovascular disease risk factor prevalence survey and for whom frozen plasma was available. Stepwise multiple linear regression analysis was used to identify the determinants of basal plasma gastrin concentration. RESULTS: The determinants of basal plasma gastrin concentration were H. pylori infection (B=0.12+/-0.03; P=0.0001), age in deciles (B=0.02+/-0.01; P=0.03), hazardous drinking (B=0.10+/-0.05; P= 0.07) and gender (B=0.05+/-0.03; P=0.06), but not education, neighborhood socioeconomic index, smoking, body mass index, vigorous exercise or medication known to affect basal plasma gastrin concentration. Ten percent (+/-3) of seropositive subjects had a high basal plasma gastrin concentration > 90 pg/mL compared with only 2% (+/-1) of seronegative subjects. CONCLUSIONS: Helicobacter pylori infection is one of the few modifiable determinants of basal plasma gastrin levels in the general population.

Comparison of rural and non-rural students undertaking a voluntary rural placement in the early years of a medical course.

OBJECTIVE: The experiences of rural and non-rural students undertaking a voluntary rural placement in the early years of a medical course were compared. METHOD: Eighty percent (28) of the rural and 70% (114) of the non-rural students completed a post-placement questionnaire. RESULT: The two groups did not differ on their overall rating of the placement, whether they felt welcome, adequacy of the time with doctors or their rating of the accommodation provided. However, 46% (13) of the rural students reported the placement had changed their feelings towards rural practice to the maximum/almost maximum extent compared with only 24% (27) of the non-rural students.

The establishment of an industry-based education program in public health.

Commonwealth reforms have led to staff of the Department of Health and Aged Care needing a greater knowledge of public health, to more effectively evaluate evidence and to quickly acquire competence in new emerging areas. The department's requirements of a training program could not be met by existing university-based public health courses. A consortium of five universities and the department worked together to develop an industry-based course that would meet the Commonwealth's needs. The course was constituted within university regulations; had an incremental and articulated structure with exit points at certificate, diploma and Masters levels; was relevant to the work of staff; offered subjects which complemented the staff's existing skills, training and career aspirations; drew upon expertise across the universities; and was flexible in its delivery. The Commonwealth's and universities' experience has been sufficiently positive to conclude that a corporate public health postgraduate program has a place alongside university-based programs.

Preventing fractures in large rural centres: sociodemographic sub-groups at risk of osteoporosis from their lifestyle.

Middle-aged people living in non-metropolitan Victoria have higher hospitalisation rates from osteoporotic fractures than those in metropolitan areas. This may reflect a higher prevalence of lifestyle risk factors for osteoporosis. One-fifth of Victoria's non-metropolitan population live in 'large rural centres'. The aim of the present study was to identify the sociodemographic sub-groups in a 'large rural centre' at risk of osteoporosis because of their lifestyle. Adults on Ballarat's electoral rolls were invited to complete a questionnaire and have their height and weight measured. A total of 335 eligible people participated in the present study (67% response). The sub-groups at risk of osteoporosis were identified using logistic regression analyses. Among women, being single/separated/divorced/widowed was associated with being underweight and having low dietary calcium. A lack of exercise was associated with not completing high school and smoking with being aged 25-44 years. Among men, low dietary calcium was associated with not completing high school and smoking was associated with being employed in a non-professional/non-managerial occupation. These sub-groups must be considered when planning preventative strategies for people in 'large rural centres'.