Detection of mutations in SF3B1, EIF1AX and GNAQ in primary orbital melanoma by candidate gene analysis

BACKGROUND: Ocular melanoma is a rare but often deadly malignancy that arises in the uvea (commonest primary site), conjunctiva or the orbit. Primary orbital melanoma (POM) is exceedingly rare, with approximately 60 cases reported to date. Despite recent advances in our understanding of the genetics of primary uveal and conjunctival melanomas, this information is lacking for POM. METHODS: DNA was extracted from 12 POM tissues, with matched germline DNA (where available). MLPA was conducted to detect chromosomal alterations and Sanger sequencing used to identify point mutations in candidate melanoma driver genes (BRAF, NRAS, KRAS, GNA11, GNAQ), and other genes implicated in melanoma prognosis (EIF1AX, SF3B1). Immunohistochemistry was performed to analyse BAP1 nuclear expression. RESULTS: MLPA detected copy number alterations in chromosomes 1p, 3, 6 and 8. Sequencing of melanoma driver genes revealed GNAQ (p.Q209L) mutations in two samples; although it is possible that these samples represent extraocular spread of an occult uveal melanoma. A recurrent mutation in SF3B1 (p.R625H) was observed in indolent, but not aggressive, tumours; a mutation in EIF1AX (p.N4S) was detected in one patient with non-aggressive disease. CONCLUSIONS: EIF1AX and SF3B1 mutations appear have a role in determining the clinical course of POM and detection of these changes could have clinical significance. Further in depth analysis of this rare group using differing 'omic technologies will provide novel insights into tumour pathogenesis

Fitness consultations in routine care of patients with type 2 diabetes in general practice: an 18-month non-randomised intervention study

<p>Abstract</p> <p>Background</p> <p>Increasing physical activity is a cornerstone in the treatment of type 2 diabetes and in general practice it is a challenge to achieve long-term adherence to this life style change. The aim of this study was to investigate in a non-randomised design whether the introduction of motivational interviewing combined with fitness tests in the type 2 diabetes care programme was followed by a change in cardio-respiratory fitness expressed by VO_2max, muscle strength of upper and lower extremities, haemoglobin A_1c(HbA_1c) and HDL-cholesterol.</p> <p>Methods</p> <p>Uncontrolled 18-month intervention study with follow-up and effect assessment every 3 months in a primary care unit in Denmark with six general practitioners (GPs). Of 354 eligible patients with type 2 diabetes, 127 (35.9%) were included. Maximum work capacity was tested on a cycle ergometer and converted to VO_2max. Muscle strength was measured with an arm curl test and a chair stand test. The results were used in a subsequent motivational interview conducted by one of the GPs. Patients were encouraged to engage in lifestyle exercise and simple home-based self-managed exercise programmes. Data were analysed with mixed models.</p> <p>Results</p> <p>At end of study, 102 (80.3%) participants remained in the intervention. Over 18 months, VO_2maxincreased 2.5% (p = 0.032) while increases of 33.2% (p < 0.001) and 34.1% (p < 0.001) were registered for the arm curl test and chair stand test, respectively. HDL-cholesterol increased 8.6% (p < 0.001), but HbA_1cremained unchanged (p = 0.57) on a low level (6.8%). Patients without cardiovascular disease or pain from function limitation increased their VO_2maxby 5.2% (p < 0.0001) and 7.9% (p = 0.0008), respectively.</p> <p>Conclusions</p> <p>In this 18-month study, participants who had repeated fitness consultations, including physical testing and motivational interviewing to improve physical activity, improved VO_2max, muscle strength, and lipid profile. Our results indicate that physical testing combined with motivational interviewing is feasible in a primary health care setting. Here, a fitness consultation tailored to the individual patient, his/her comorbidities and conditions in the local area can be incorporated into the diabetes programme to improve patients' muscle strength and cardio-respiratory fitness.</p

How long do nosocomial pathogens persist on inanimate surfaces? A systematic review

BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed

Presentation, treatment and prognosis for secondary melanoma within the orbit

Background: Ocular melanoma is a rare but often deadly malignancy that arises in the uvea, conjunctiva, or orbit. Uveal melanoma is the most common type, with conjunctival melanoma being the second most frequently observed. Melanoma accounts for 5–10% of metastatic or secondary orbital malignancies, but only a minute proportion of primary orbital neoplasia. The aim of this study was to characterize the clinical presentation, treatment, and prognosis in patients presenting with melanoma metastatic to, or secondary within, the orbit. Methods: A retrospective cohort study of patients presenting to a tertiary referral orbital unit from 1982 to 2016 was performed. Eighty-nine patients with biopsy-proven diagnosis of melanoma within the orbit were included in the study. The clinical notes, radiological imaging, histology, surgical notes, and outcome data for the patients were reviewed. The main outcome measures of interest were the interval between primary malignant melanoma and orbital presentation, survival after orbital presentation, and clinical parameters (such as gender, age at presentation, and treatment approach). Results: The commonest primary source of tumor was choroidal melanoma, with conjunctival and cutaneous melanomas being relatively common; eyelid and naso-sinus tumors occurred in a few cases. The mean age at presentation with orbital disease was 65 years (31–97 years). The interval between primary malignancy and orbital disease (either local spread/recurrence or true metastatic disease) showed wide variability, with almost one-third of patients having orbital disease at the time of primary diagnosis, but others presenting many years later; indeed, the longest orbital disease-free interval was over 34 years. Twenty-three patients were considered to have had late orbital metastases—that is, at more than 36 months after primary tumor. The median survival following presentation with orbital involvement was 24 months. Patients with tumors of cutaneous origin had worst survival, whereas those with conjunctival tumors had the best prognosis. Conclusion: A high index of suspicion for orbital recurrence should be maintained in any patient with prior history of melanoma, however distant the primary tumor is in site or time. Furthermore, giving a prognosis for orbital melanoma remains problematic due to highly variable survival, and further investigation will be necessary to understand the likely genetic basis of this phenomenon