Human papillomavirus 16 and p16 positive nasal cutaneous squamous cell carcinoma in immunocompetent men in their twenties.

BACKGROUND: Cutaneous squamous cell carcinoma is usually associated with long-term ultraviolet light exposure. Human papillomavirus 16 is a high-risk mucosal human papillomavirus type, usually associated with anogenital and oropharyngeal cancer. This paper describes the first two cases of human papillomavirus 16 and p16 related nasal cutaneous squamous cell carcinoma. METHOD: Prospective case series from December 2015. RESULTS: Two young, male, fair-skinned patients had large (greater than 20 mm), rapidly growing, ulcerated lesions of the nasal tip. The tumours were excised, with at least a 6 mm margin, and the patients' noses were subsequently reconstructed. Neither patient had cervical lymphadenopathy or underwent adjuvant radiotherapy. Both patients were registered at the same general practice. The tumours were human papillomavirus 16 and p16 positive; the latter indicated that the virus was driving the disease process. Except for superficial burns, neither patient had other risk factors. CONCLUSION: Changes in sexual practices have led to an increase in human papillomavirus positive oropharyngeal carcinoma and there may be an associated increase in human papillomavirus type 16 positive nasal cutaneous squamous cell carcinoma.

Short-term changes observed in multiparametric liver MRI following therapy with direct-acting antivirals in chronic hepatitis C virus patients.

METHODS: We applied multiparametric MRI to assess changes in liver composition, perfusion and blood flow in 17 patients before direct-acting antiviral (DAA) therapy and after treatment completion (within 12 weeks of last DAA tablet swallowed). RESULTS: We observed changes in hepatic composition indicated by a reduction in both liver longitudinal relaxation time (T1, 35 ± 4 ms), transverse relaxation time (T2, 2.5 ± 0.8 ms; T2* 3.0 ± 0.7 ms), and liver perfusion (28.1 ± 19.7 ml/100 g/min) which we suggest are linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. No changes were observed in liver or spleen blood flow, splenic perfusion, or superior mesenteric artery blood flow. CONCLUSION: For the first time, our study has shown that treatment of HCV with DAAs in patients with cirrhosis leads to an acute reduction in liver T1, T2 and T2* and an increase in liver perfusion measured using MR parameters. The ability of MRI to characterise changes in the angio-architecture of patients with cirrhosis after intervention in the short term will enhance our understanding of the natural history of regression of liver disease and potentially influence clinical decision algorithms. KEY POINTS: • DAAs have revolutionised the treatment of hepatitis C and achieve sustained virological response in over 95% of patients, even with liver cirrhosis. • Currently available non-invasive measures of liver fibrosis are not accurate after HCV treatment with DAAs, this prospective single-centre study has shown that MRI can sensitively measure changes within the liver, which could reflect the reduction in inflammation with viral clearance. • The ability of MRI to characterise changes in structural and haemodynamic MRI measures in the liver after intervention will enhance our understanding of the progression/regression of liver disease and could potentially influence clinical decision algorithms.

Current and Future Magnetic Resonance Technologies for Assessing Liver Disease in Clinical and Experimental Medicine.

BACKGROUND: In the past decades, a number of non-invasive methods have emerged for detecting and estimating liver fibrosis; these include both serum-based panels and imaging-based technology. Some of these methods are now being incorporated in clinical practice. However, the limitations of the current techniques include lack of organ specificity, sampling errors and limited ability to reflect the efficacy of interventions. Key Messages: Novel magnetic resonance (MR)-based techniques provide an opportunity to bring about further changes in the investigations and management of patients with liver diseases. Multimodal quantitative MR techniques enable the estimation of fat, iron accumulation, degree of liver injury/inflammation and fibrosis within the whole liver without the need for administering contrast agents. Architectural changes within the liver can be evaluated concurrently with portal haemodynamic changes allowing non-invasive assessment of portal hypertension and effects of interventions. A combination ultra-high field (7T) provides greater sensitivity with a potential to distinguish inflammation from fibrosis on imaging and determine specific types of fats (saturated vs. unsaturated) present within the liver using MR spectroscopy. 13C MR spectroscopy can estimate glutathione flux and rate of beta oxidation in-vivo providing novel tools for experimental studies that evaluate the efficacy of interventions as well as underlying mechanisms. CONCLUSIONS: Translational research should focus on converting the potentials of these innovative methodologies into clinical applications for the benefit of patients.

Burning mouth syndrome: patch test results from a large case series.

BACKGROUND: Burning mouth syndrome (BMS) is a burning or sore mouth in the absence of changes in the oral mucosa. It is often difficult to diagnose and treat. Numerous theories of the etiology have been suggested, including contact allergy. OBJECTIVE: To determine the clinical utility of patch testing in patients with BMS. METHODS: We retrospectively reviewed the charts of patients diagnosed with BMS who had patch testing performed between January 1, 2008, and July 31, 2012. RESULTS: Of 142 consecutive patients with BMS, 132 consented to patch testing; 89 (67%) had allergic patch test reactions. Of the patients with positive results, 66 (74%) had results that were deemed to have possible relevance. The most common allergens detected were nickel sulfate 2.5%, dodecyl gallate 0.3%, octyl gallate 0.3%, fragrance mix 8%, benzoyl peroxide 1%, and cinnamic alcohol 1%. CONCLUSIONS: Our findings suggest that contact allergy may be an etiologic factor in some patients with BMS. Patch testing is a useful investigation for BMS patients.

Displacement of mandibular fractures: is there a correlation with sensory loss and recovery?

Fractures of the mandible are common. However, the correlation between the severity of the fracture and the recovery of any associated inferior dental (ID) nerve injury is still poorly understood. We aimed to examine the relationship between the amount of fracture displacement and how it relates to the recovery of sensation to the lower lip. One hundred and fifty patients requiring treatment of a mandibular fracture (where the fracture passed across the ID canal) were assessed. One hundred were initially assessed in a retrospective double-blinded study. A further 50 patients were then followed up prospectively. Both the maximal displacement of the fracture and the displacement specifically at the ID canal were measured. Sensory recovery, or persistence of numbness, was also recorded for each patient. Although there appeared to be a correlation between increasing displacement at the ID canal and a poorer recovery, there was not a clear relationship between the two, and there were many exceptions. Persistent numbness (>1 year) still occurred in fractures with relatively minimal displacement (≤3mm). Possible reasons for persistent numbness are discussed.

Teaching dermatology to internal medicine residents: needs assessment survey and possible directions.

BACKGROUND: Internal medicine trainees receive limited teaching and training in dermatology and may feel inadequately prepared to assess and manage patients with dermatologic complaints. No study to date has assessed the needs of internal medicine trainees in Canada with regard to dermatology teaching. OBJECTIVE: To determine internal medicine residents' comfort in assessing and managing dermatologic issues and their educational needs in dermatology. METHODS: An electronic survey was conducted of first-, second-, and third-year internal medicine residents at the University of Toronto. RESULTS: Fifty-four of 186 internal medicine trainees responded to our survey (response rate  =  29%). Each respondent did not answer every question. Residents were generally uncomfortable or very uncomfortable assessing and managing dermatologic issues in the emergency department (40 of 47, 85%), ward or intensive care unit (39 of 47, 83%), and ambulatory clinic (40 of 47, 85%). Residents thought that various clinical and didactic dermatology exposures would be useful to their training as internists. Case-based teaching and ambulatory clinical rotations were felt to be particularly valuable. Additionally, 38 of 46 (83%) respondents wanted to learn how to perform punch biopsies. CONCLUSIONS: An effort should be made to increase the availability of relevant dermatology teaching and clinical exposures for internal medicine residents.

The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study.

AIMS/HYPOTHESIS: Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association. METHODS: A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created. RESULTS: A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history. CONCLUSIONS/INTERPRETATION: Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.

Final follow-up of the Multicentre Aneurysm Screening Study (MASS) randomized trial of abdominal aortic aneurysm screening.

BACKGROUND: The long-term effects of abdominal aortic aneurysm (AAA) screening were investigated in extended follow-up from the UK Multicentre Aneurysm Screening Study (MASS) randomized trial. METHODS: A population-based sample of men aged 65-74 years were randomized individually to invitation to ultrasound screening (invited group) or to a control group not offered screening. Patients with an AAA (3·0 cm or larger) detected at screening underwent surveillance and were offered surgery after predefined criteria had been met. Cause-specific mortality data were analysed using Cox regression. RESULTS: Some 67 770 men were enrolled in the study. Over 13 years, there were 224 AAA-related deaths in the invited group and 381 in the control group, a 42 (95 per cent confidence interval 31 to 51) per cent reduction. There was no evidence of effect on other causes of death, but there was an overall reduction in all-cause mortality of 3 (1 to 5) per cent. The degree of benefit seen in earlier years of follow-up was slightly diminished by the occurrence of AAA ruptures in those with an aorta originally screened normal. About half of these ruptures had a baseline aortic diameter in the range 2·5-2·9 cm. It was estimated that 216 men need to be invited to screening to save one death over the next 13 years. CONCLUSION: Screening resulted in a reduction in all-cause mortality, and the benefit in AAA-related mortality continued to accumulate throughout follow-up. REGISTRATION NUMBER: ISRCTN37381646 (http://www.controlled-trials.com).

DNA yield and quality of saliva samples and suitability for large-scale epidemiological studies in children.

OBJECTIVE: To evaluate two saliva collection methods for DNA yield and quality as applied to a large, integrated, multicentre, European project involving the collection of biological material from children. DESIGN: Cross-sectional multicentre comparative study in young children. METHODS: Saliva samples were collected from 14,019 children aged 2-9 years from eight European countries participating in the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study. This involved either the collection of 2 ml of saliva from children who were able to spit, or using a sponge to collect whole saliva and buccal mucosal cells from the inside of the mouth of younger children unable to spit. Samples were assembled centrally in each participating centre and subsequently despatched for DNA extraction and biobanking to the University of Glasgow. A subgroup of 4678 samples (∼33% of sampled individuals) were chosen for DNA extraction before genotyping. RESULTS: The whole-saliva collection method resulted in a higher DNA yield than the sponge collection method (mean±s.d.; saliva: 20.95±2.35 µg, sponge: 9.13±2.25 µg; P<0.001). DNA quality as measured by A (260)/A (280) was similar for the two collection methods. A minimum genotype calling success rate of 95% showed that both methods provide good-quality DNA for genotyping using TaqMan allelic discrimination assays. CONCLUSIONS: Our results showed higher DNA yield from the whole-saliva collection method compared with the assisted sponge collection. However, both collection methods provided DNA of sufficient quantity and quality for large-scale genetic epidemiological studies.

Ophthalmic injuries in British Armed Forces in Iraq and Afghanistan.

AIM: British military ophthalmologists have not been deployed in support of operations since 2003. Eye injuries in British forces receive definitive treatment on return to the United Kingdom. We report the injury patterns, management strategies, and outcomes for eye injuries in British Armed Forces in Iraq and Afghanistan. METHODS: Retrospective consecutive case series of eye injuries in British Armed Forces in Iraq or Afghanistan from July 2004 to May 2008. Outcomes assessed by final best-corrected visual acuity (VA; few patients lost to follow-up), rates of endophthalmitis, and proliferative vitreoretinopathy (PVR). RESULTS: There were 630 cases of major trauma, 63 sustained eye injuries (10%), and 48 sustained significant eye injuries. There were 21 open-globe injuries: 9 ruptures and perforating injuries, of which 7 were enucleated/eviscerated; 11 intraocular foreign body (IOFB) injuries, of which 1 was eviscerated. Primary repair was combined with posterior segment reconstruction in 9/11 cases with IOFB. Mean time to primary repair was 1.9 days (range 0-5). Intravitreal antibiotics were given at primary repair in five cases. All cases received early broad-spectrum systemic antibiotics. Median final VA was logMAR 0.25 excluding evisceration/enucleations. There were two cases of PVR and none of endophthalmitis. CONCLUSIONS: The number of eye injuries as a proportion of all casualties is lower than recently reported. The injuries are more severe than in civilian practise. The outcomes were comparable with previous reports, this demonstrates that, in certain cases, primary repair can be safely delayed beyond 24 h in the patient's best interests, in order to optimise the conditions for treatment.

Contact lens-related microbial keratitis in deployed British military personnel.

AIMS: To quantify the effect of contact lens-related microbial keratitis (CLMK) in the British Defence personnel particularly those in active service in the Arabian Gulf and Afghanistan between June 2001 and January 2007. METHODS: A retrospective review of all British military personnel who developed contact lens-related keratitis during deployment. RESULTS: A total of 27 cases (27, eyes, 23, male; median age 26 (range 19-41) years) were identified, of whom 19 cases were evacuated from Iraq alone. Twenty cases were associated with soft contact lens wear. Seven cases were culture positive, of which five grew Pseudomonas aeruginosa. The overall incidence of CLMK in contact lens wearer in the British military in Iraq was 35 per 10,000. There was an increased incidence during the summer months. Seventeen eyes (63%) lost more than one line of visual acuity with a resultant permanent medical downgrading in duty capability in nine cases. CONCLUSIONS: CLMK has a poorer outcome in a deployed military environment when compared to the civilian setting. Increased awareness of the health risks of contact lens wear together with standardised treatment regimens based on improved pathogen detection using molecular diagnostics have improved outcomes.

Screening men for abdominal aortic aneurysm: 10 year mortality and cost effectiveness results from the randomised Multicentre Aneurysm Screening Study.

OBJECTIVES: To assess whether the mortality benefit from screening men aged 65-74 for abdominal aortic aneurysm decreases over time, and to estimate the long term cost effectiveness of screening. DESIGN: Randomised trial with 10 years of follow-up. SETTING: Four centres in the UK. Screening and surveillance was delivered mainly in primary care settings, with follow-up and surgery offered in hospitals. PARTICIPANTS: Population based sample of 67 770 men aged 65-74. INTERVENTIONS: Participants were individually allocated to invitation to ultrasound screening (invited group) or to a control group not offered screening. Patients with an abdominal aortic aneurysm detected at screening underwent surveillance and were offered surgery if they met predefined criteria. MAIN OUTCOME MEASURES: Mortality and costs related to abdominal aortic aneurysm, and cost per life year gained. RESULTS: Over 10 years 155 deaths related to abdominal aortic aneurysm (absolute risk 0.46%) occurred in the invited group and 296 (0.87%) in the control group (relative risk reduction 48%, 95% confidence interval 37% to 57%). The degree of benefit seen in earlier years of follow-up was maintained in later years. Based on the 10 year trial data, the incremental cost per man invited to screening was pound100 (95% confidence interval pound82 to pound118), leading to an incremental cost effectiveness ratio of pound7600 ( pound5100 to pound13,000) per life year gained. However, the incidence of ruptured abdominal aortic aneurysms in those originally screened as normal increased noticeably after eight years. CONCLUSIONS: The mortality benefit of screening men aged 65-74 for abdominal aortic aneurysm is maintained up to 10 years and cost effectiveness becomes more favourable over time. To maximise the benefit from a screening programme, emphasis should be placed on achieving a high initial rate of attendance and good adherence to clinical follow-up, preventing delays in undertaking surgery, and maintaining a low operative mortality after elective surgery. On the basis of current evidence, rescreening of those originally screened as normal is not justified. Trial registration Current Controlled Trials ISRCTN37381646.

High-resolution optical coherence tomography demonstration of membranes spanning optic disc pits and colobomas.

OBJECTIVES: To demonstrate the features of optic disc pits and colobomas revealed by high-resolution optical coherence tomography (OCT) and their association with the development of maculopathy. METHODS: Subjects with disc pits or colobomas and no other ocular history underwent full ophthalmic examinations including logMAR visual acuity and contrast sensitivity. Fundus photographs and high-resolution OCT images were obtained. RESULTS: Seven patients were identified with optic disc pits or colobomas aged 25 to 63 years. Five patients had a unilateral optic disc pit, one had a unilateral disc coloboma, and another had bilateral disc colobomas. Apart from one eye with a grossly anomalous disc, vision was logMAR 0.4 or better in all eyes. In three of five eyes without maculopathy, a complete membrane could be identified traversing the optic disc cup that was absent or deficient in the three eyes with maculopathy. One patient with optic disc pit and marked schisis-like separation of the retinal layers throughout the macula was asymptomatic with logMAR visual acuity of 0.0 and normal achromatic contrast sensitivity. CONCLUSIONS: In this small series of patients with optic disc pits or colobomas, it was possible to identify a membrane spanning the optic disc cup, and it is speculated that this may protect against the development of maculopathy. Schisis-like separation of retinal layers can be associated with normal visual function.

The place of screening in the management of abdominal aortic aneurysm.

UNLABELLED: The present method of management of Abdominal Aortic Aneurysms (AAA) is ineffective in preventing AAA rupture. 5000 people still die of AAA in the UK each year. Improvements in surgery can only reduce the mortality in the minority who reach hospital following chance detection, and then only by a few percent. Screening, with detection in the community and planned treatment can reduce the mortality of the disease by 58%. Screening programmes for AAA have recently been approved for men aged 65 years, in both the UK and the USA. The proposed UK National Screening Programme is outlined briefly. CONCLUSION: If the aim of treatment is to reduce the mortality of the disease as a whole, resources would be better spent on screening programmes for AAA, rather than developing increasingly sophisticated operative techniques that could only reduce the overall death from AAA by a few percent.