Observational study to estimate the proportion of surgical site infection following excision of ulcerated skin tumours (OASIS study).

BACKGROUND: Ulceration is a recognized risk factor for surgical site infection (SSI); however, the proportion of patients developing SSI after excision of an ulcerated skin cancer is unknown. AIM: To determine the proportion of participants with SSI after surgical excision of an ulcerated skin cancer. A secondary aim was to assess feasibility outcomes to inform the design of a randomized controlled trial to investigate the benefits and harms of perioperative antibiotics following excision of ulcerated tumours. METHODS: This was a multicentre, prospective, observational study of patients undergoing excision of an ulcerated skin cancer between March 2019 and March 2020. Prior to surgical excision, surface swabs of the ulcerated tumours of participants recruited from one centre were undertaken to determine organism growth. At 4 weeks after surgery, all participants were e-mailed or posted the Wound Healing Questionnaire (WHQ) to determine whether they had developed SSI. RESULTS: In total, 148 participants were recruited 105 (70.9%) males; mean ± SD age 77.1 ± 12.3 years. Primary outcome data were available for 116 (78.4%) participants, of whom 35 (30.2%) were identified as having an SSI using the WHQ with a cutoff score of 8, and 47 (40.5%) were identified with a cutoff score of 6. Using the modified WHQ in participants with wounds left to heal by secondary intention, 33 (28.4%) and 43 (37.1%) were identified to have SSI respectively. CONCLUSION: This prospective evaluation of SSI identified with the WHQ following excision of ulcerated skin cancers demonstrated a high proportion with SSI. The WHQ was acceptable to patients; however, further evaluation is required to ensure validity in assessing skin wounds.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

A 10-year longitudinal follow-up study of a U.K. paediatric transplant population to assess for skin cancer.

BACKGROUND: Our earlier study, published in 2004,found no skin cancer in a cohort of paediatric organ transplant recipients (POTRs) 5-16 years post-transplantation. We re-evaluated the same cohort 10 years later. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and identify known risk factors associated with melanocytic naevi in a U.K. paediatric transplant population. METHODS: Ninety-eight POTRs from the original 2004 study were invited to participate in this longitudinal follow-up study. History of sun exposure, demographics and transplantation details were collected using face-to-face interviews, questionnaires and case note reviews. Skin examination was performed for regional count of malignant lesions, benign and atypical naevi. RESULTS: Of the 98 patients involved in the initial study, 45 POTRs (eight kidney, 37 liver), with a median follow-up of 19 years (range 15-26 years), agreed to participate. Neither skin cancer nor premalignant lesions were detected in these patients. When compared with the 2004 cohort, 41 patients in our current cohort had increased numbers of benign naevi (P < 0·001) with 11 patients having ≥ 50 benign naevi. Seventy-one per cent of benign naevi in our 2014 cohort occurred on sun-exposed sites (13% head/neck, 35% arms and 23% legs). Patients who regularly used sunscreen had more benign naevi on their arms (P = 0·008). CONCLUSIONS: Although skin cancer was not observed in our cohort, we identified a significant increase in the number of benign naevi, particularly in those reporting frequent sunburn and sunscreen use.

Generating new evidence, improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network's STOP GAP and BLISTER trials.

Clinical trials may benefit clinical practice in three ways: firstly, clinicians may change their practice according to the new trial evidence; secondly, clinical processes can improve when working on a trial; and thirdly, research capacity is increased. We held a meeting to present and discuss the results of two large multicentre randomized controlled trials delivered through the U.K. Dermatology Clinical Trials Network. Investigators gave reflections on how the trials had changed their clinical practice. The STOP GAP trial showed that prednisolone and ciclosporin are equally effective as first-line systemic treatment for pyoderma gangrenosum. The final decision of which treatment to use should be based on the different adverse event profiles of the two drugs in relation to comorbidities, along with age, disease severity and patient preference. The BLISTER trial showed that starting people with pemphigoid on doxycycline produces acceptable short-term effectiveness and a superior safety profile to oral corticosteroids. Recruiting to these trials has led to the development of new specialist clinics with improved documentation. It has increased the profile of participating departments and embedded research in the department's activities. Helping to design and run these trials has also allowed trial staff to develop new skills in research design, which has been beneficial for career development. These and other benefits of recruiting to the trials are summarized here. We hope that these reflections will inspire wider involvement in clinical research.

[Google Scholar and the h-index in biomedicine: the popularization of bibliometric assessment]. / Google Scholar e índice h en biomedicina: la popularización de la evaluación bibliométrica.

The aim of this study is to review the features, benefits and limitations of the new scientific evaluation products derived from Google Scholar, such as Google Scholar Metrics and Google Scholar Citations, as well as the h-index, which is the standard bibliometric indicator adopted by these services. The study also outlines the potential of this new database as a source for studies in Biomedicine, and compares the h-index obtained by the most relevant journals and researchers in the field of intensive care medicine, based on data extracted from the Web of Science, Scopus and Google Scholar. Results show that although the average h-index values in Google Scholar are almost 30% higher than those obtained in Web of Science, and about 15% higher than those collected by Scopus, there are no substantial changes in the rankings generated from one data source or the other. Despite some technical problems, it is concluded that Google Scholar is a valid tool for researchers in Health Sciences, both for purposes of information retrieval and for the computation of bibliometric indicators.

Decline of dermatological publications in the UK: truth or myth?

BACKGROUND: For some time, there has been a suspicion that the number of articles published by UK-based authors in dermatology has declined. This probably reflects a reduction in the publication output of dermatology departments generally. METHODS: We identified articles with British authorship in the British Journal of Dermatology between 1970 and the present date, and compared the journal with the three most commonly cited dermatological journals: Archives of Dermatology, Journal of Investigative Dermatology and Journal of the American Academy of Dermatology. Later, we expanded this search to include a further 33 dermatological journals. RESULTS: Despite an increase in the total number of published papers by the British Journal of Dermatology, there was a decline in the number of British-authored papers, from 97 (57%) in 1970 to 80 (22%) in 2005. The trend was also seen in the Journal of the American Academy of Dermatology, with 16 papers (5%) in 1989 and 7 (2%) in 2005. In Journal of Investigative Dermatology, British papers increased from 10 papers in 1975 to 17 in 2005, with a percentage decrease from 7% to 4%. Overall, despite an increase in the total number of publications in dermatological journals from 2745 in 1985-5034 in 2005, British publications increased from 271 in 1989 to only 289 in 2005, which represents a percentage decrease from 10% to 6%. CONCLUSIONS: Despite a three-fold increase in dermatology consultants and registrars in UK, a three-fold increase in dermatological journals and a four-fold increase in dermatological papers published, the overall number of British papers has remained static over the years.

Expression and purification of an anti-Foot-and-mouth disease virus single chain variable antibody fragment in tobacco plants.

Low-cost recombinant antibodies could provide a new strategy to control Foot-and-mouth disease virus (FMDV) outbreaks by passive immunization of susceptible animals. In this study, a single chain variable antibody fragment (scFv) recognizing FMDV coat protein VP1 was expressed in transgenic tobacco plants. To enhance the accumulation of scFv protein, the codon-usage of a murine hybridoma-derived scFv gene was adjusted to mimic highly expressed tobacco genes and fused to an elastin-like polypeptide (ELP) tag. This scFv-ELP fusion accumulated up to 0.8% of total soluble leaf protein in transgenic tobacco. To recover scFv-ELP protein from the leaf extract, a simple and scalable purification strategy was established. Purified scFv-ELP fusion was cleaved to separate the scFv portion. Finally, it was shown that the purified scFv proteins retained their capacity to bind the FMDV in the absence or presence of ELP fusion.

Treatment of disseminated superficial actinic porokeratosis with topical diclofenac gel: a case series.

Disseminated superficial actinic porokeratosis (DSAP) is the most common of the of five clinical variants of porokeratosis. These are disorders of keratinization and the distinctive pathological feature is the cornoid lamella at the margin. DSAP usually manifests in the third or fourth decades of life with a female preponderance and with multiple lesions over sun-exposed areas. A diverse range of treatments is employed though evidence of efficacy remains largely anecdotal. We report a series of eight patients with DSAP treated with 3% diclofenac gel (Solaraze gel).

Current Status and Future Prospects to Achieve Foot-and-Mouth Disease Eradication in South America.

South America has a favourable position with respect to foot-and-mouth disease (FMD) compared with other FMD-affected regions due to the elimination of endemic clinical presentation of the disease. South America has reached the final stage of control and aims to eradicate the disease in the region under the provisions of the Hemispheric Program for the Eradication of FMD 2011-2020 (PHEFA). This programme aims at bringing eradication to completion, thereby eliminating the pool of foot-and-mouth disease genotypes active in South America. This plan includes a regional political agreement that provides strategies and technical guidelines for the eradication of foot-and-mouth disease from South America. It incorporates knowledge and experience regarding the disease's history and its connection with the different production systems, animal movement and trade. The Pan American Foot and Mouth Disease Center has led the control and eradication programmes, providing the framework for designing national and subregional programmes that have led to significant progress in controlling the disease in South America. The current situation is the result of several factors, including the proper implementation of a national control programmes, good veterinary infrastructure in most countries and public-private participation in the process of eradicating the disease. Notwithstanding the favourable health status, there are significant challenges for the goal of eradication. At this stage, South American countries should enhance their surveillance strategies particularly through the use of target or risk-based surveys that contribute to increase the degree of sensitivity in the search for viral circulation in the context of absence of clinical occurrence of FMD.

Molecular cloning and restriction enzyme mapping of avian adenovirus type 8 DNA.

Avian adenovirus (AAV) type 8 was cultured in an avian hepatoma cell line designated CH-SAH and the viral DNA extracted and purified. Restriction enzyme analysis of viral DNA using the endonucleases ApaI, EcoRI, HindIII, KpnI, NotI, SpeI, StuI and XbaI was carried out, and fragments representing the entire genome were cloned. According to the restriction enzyme fragments, the size of the AAV type 8 genome was calculated to be 44.7 kb. Subcloning of viral DNA fragments and hybridization studies using selected viral DNA fragments facilitated the construction of the physical map of AAV type 8 DNA.

Isolation and identification of bluetongue virus.

Bluetongue virus (BTV) is an arthropod-borne orbivirus that infects sheep, wild ruminants and occasionally cattle. Detection and specific identification of BTV is a multistep process. The first step involves the isolation of the virus from the animal's blood or other tissues, followed by inoculation of embryonating chicken eggs (ECE). After the virus has been amplified in ECE, it is passaged into BHK-21 cell culture for subsequent replication and identification. The virus is then amplified further and identified in microtiter plates by the immunoperoxidase assay using a group specific monoclonal antibody. Finally, the viral isolate is typed by a virus neutralization test.

Development and evaluation of an IgM-capture ELISA for detection of recent infection with bluetongue viruses in cattle.

An IgM-capture enzyme-linked immunosorbent assay (ELISA) was developed for the detection of recent infection of bluetongue virus (BTV) in cattle. The test is based on the use of biotinylated capture anti-bovine IgM antibodies bound to a streptavidin-coated ELISA plate. The captured IgM antibodies were detected by application of BTV VP7 antigen and a VP7 antigen-specific monoclonal antibody. The IgM-capture ELISA was compared with the competitive ELISA by testing serum samples from groups of calves infected experimentally with five USA and 19 South Africa serotypes of BTV. The IgM-capture ELISA was able to detect bovine anti-VP7 antibodies from all animals infected with the 24 BTV serotypes at 10 days post-infection, whereas the competitive ELISA was not. When the detectable IgM diminished after 40 days post-infection by the IgM-capture ELISA, the IgG anti-VP7 antibodies remained high. The IgM-capture ELISA is sensitive and can be applied for the detection of recent infection of BTV in cattle.

Assessment of the pathogenicity of an emu-origin influenza A H5 virus in ostriches (Struthio camelus).

Ostriches were inoculated with a laboratory-derived highly pathogenic avian influenza (HPAI) virus of emu origin, A/emu/TX/39924/93 (H5N2) clone c1B. The aim of this study was to evaluate the pathogenicity of this isolate for ostriches and assess the ability of routine virological and serological tests to detect infection. Avian influenza virus (AIV) was isolated from cloacal and tracheal swabs from 2 to 12 days post-infection. AIV was also isolated from brain, thymus, eyelid, spleen, ovary/testis, liver, air sac, proventriculum, duodenum, caecal tonsil, heart, pancreas, kidney, nasal gland and lung. Virus isolation was also possible from swabs of the luminal surfaces of the cloaca, jejunum, lower ileum, bursa of Fabricius, trachea and bone marrow. Birds seroconverted as early as 7 days post-infection. This study suggests that HPAI virus of emu origin replicates extensively in infected ostriches without causing significant clinical disease or mortality.

Chemiluminescent detection of caprine arthritis encephalitis virus with a PCR-generated single stranded nonradiolabelled probe.

A 814-bp digoxigenin-labelled single stranded DNA probe was produced and utilized in slot-blot hybridization for detection of caprine arthritis encephalitis virus (CAEV) in goat synovial membrane (GSM) cell culture infected with CAEV. The sensitivity of a PCR-generated probe was compared with a random primer labelled probe. The probe with digoxigenin-dUTP incorporated in the PCR reaction mixture was more sensitive for RNA detection than the random primer probe and it was much simpler to use. The probe was applied for detection of CAEV by blot blot hybridization in peripheral blood mononuclear cells (PBMC) and macrophage cultures obtained from naturally infected goats. This technique was not sufficiently sensitive to detect the viral nucleic acid directly from PBMC or cultured macrophages. When macrophages were cultured in vitro and then cocultured with susceptible GSM cells, samples gave a positive signal in the slot-blot hybridization technique. The use of slot-blot RNA hybridization permits more convenient and rapid confirmation of CAEV isolation in susceptible cells than the conventional identification by syncytia formation.

Development and evaluation of a novel antigen capture assay for the detection of classical swine fever virus antigens.

An antigen-capture enzyme immunoassay (EIA) was developed to detect classical swine fever virus (CSFV) antigen directly from 10% w/v tissue suspension. The assay, based on the sandwich principle, uses a biotinylated monoclonal antibody bound to streptavidin-coated microplates as the capture system and a swine anti-CSFV antibody and rabbit anti-swine HRPO-conjugate as the detector system. The antigen-capture EIA was compared with conventional virus isolation and polymerase chain reaction (PCR) for detection of CSFV in tissues. The ability of the antigen-capture EIA to discriminate classical swine fever (CSF) from bovine viral diarrhea and African swine fever viruses was also tested. The assay was shown to detect 21 different strains of CSFV and was unreactive with tissues from uninfected animals. Signal to noise (S/N) ratios were calculated from the EIA absorbance values. Readings from samples positive by virus isolation (n = 47) averaged a S/N ratio of 5.34. In contrast, samples negative by virus isolation (n = 96) demonstrated a mean S/N ratio of 0.16. At S/N cut-off value of 1.0, all samples that yield virus isolation and PCR negative result were negative in the antigen-capture EIA. Compared with virus propagation in tissue culture using PK15 cells (followed by indirect peroxidase assay detection) and PCR, the EIA had a specificity of 98.7% and a sensitivity of 91.4%. The EIA is simple, can be performed in 4 h and lends itself to automation for screening of tissues sample from pigs suspected of CSFV infection.

Application of competitive enzyme-linked immunosorbent assay for the serologic diagnosis of classical swine fever virus infection.

A competitive enzyme-linked immunosorbent assay (C-ELISA), based on a truncated E2 recombinant protein of the Alfort/187 strain of classical swine fever virus (CSFV) and a specific monoclonal antibody M1669, was evaluated using 2,000 sera from clinically healthy pigs in Canada (a CSFV-free country) and sera from experimentally infected pigs. The relative specificity and sensitivity of the C-ELISA were 100% and 86%, respectively, at a cutoff of 25% inhibition using negative and positive pig sera, as defined by the neutralizing peroxidase-linked assay (NPLA). A kappa value of 0.91 was obtained, indicating an excellent level of agreement between the NPLA and the C-ELISA. When sera from 120 infected pigs were used in the test at > or = 21 days postinfection, the sensitivity of the C-ELISA and the kappa value increased to 97% and 0.98, respectively. This C-ELISA will be useful when a large number of samples must be tested, as could occur during a disease outbreak or for surveillance or prevalence studies.

Differentiation of infectious laryngotracheitis virus strains by polymerase chain reaction.

Oligonucleotide primers derived from infectious laryngotracheitis virus (ILTV) DNA clones of vaccine and virulent strains were used to develop a polymerase chain reaction (PCR) for the identification and differentiation of ILTV strains. The PCR followed by restriction endonuclease analysis was used to group four strains of ILTV. A 458-bp sequence that for the LT-IVAX ILTV strain contains a unique BamHI site was amplified by PCR and digested with BamHI restriction endonuclease. From the sizes of the resultant DNA fragments the virulent strain was distinguished from the three low virulence strains.