A multicenter randomized controlled study to evaluate whether neuromuscular electrical stimulation improves the absolute walking distance in patients with intermittent claudication compared with best available treatment.

OBJECTIVE: To assess the clinical efficacy of a neuromuscular electrical stimulation (NMES) device to improve the absolute walking distance in patients with intermittent claudication as an adjunct to the local standard care available at the study sites compared with local standard care alone. METHODS: This open, multicenter, randomized controlled trial included eight participating centers in England. Sites are equally distributed between those that provide supervised exercise therapy programs and those that do not. Patients with intermittent claudication meeting the eligibility criteria and providing consent will be randomized, depending on the center type, to either NMES and locally available standard care or standard care alone. The primary end point is change in absolute walking distance at 3 months (the end of the intervention period) by treadmill testing. Secondary outcomes include quality of life, compliance with the interventions, economic evaluation of the NMES device, and lower limb hemodynamic measures to further the understanding of underlying mechanisms. Recruitment commenced in March 2018 and will continue for a total of 15 months. The Neuromuscular Electrical Stimulation Improves the Absolute Walking Distance in Patients with Intermittent Claudication trial is funded by the UK Efficacy and Mechanism Evaluation Programme, Medical Research Council, and National Institute for Health Research partnership.

Subclavian Artery Pseudoaneurysm in an Unusual Case of Digital Gangrene.

A young male patient presented at a tertiary care hospital with cold and bluish left upper limb accompanied with digital gangrene arousing suspicion of peripheral vascular disease. History did not reveal any high-risk behavior. Clinical examination and subsequent investigations lead to the diagnosis of acute infective endocarditis of native aortic valve along with peripheral embolism caused by methicillin-resistant Staphylococcus aureus. Fogarty's balloon embolectomy was done following which patient developed pseudoaneurysm of the left subclavian artery. These iatrogenic sequelae were managed with the resection of the pseudoaneurysm and prolonged antibiotic therapy as per the culture and sensitivity report.

Unilateral conjunctivitis of unique etiology: A case report from Eastern India.

A middle-aged female patient from West Bengal presented with complaints of redness, foreign body sensation, and watering for 2 days in the left eye. Slit lamp examination of the left eye revealed several minute white foreign bodies moving over the bulbar conjunctiva. Removal of the foreign bodies under local anesthesia, followed by microscopic examination, suggested the presence of first instar larvae of Oestrus ovis; the sheep nasal bot fly. Diagnosis of unilateral external ophthalmomyiasis was made. Such cases though very infrequently have been reported in the past from Southern and Central Part of India. To the best of our knowledge, this is the second report from Eastern India. A high index of suspicion is necessary both on the part of the clinician and the microbiologist for correct diagnosis.

Cutaneous histoplasmosis in a HIV seronegative patient.

A patient presented with multiple nodulo-ulcerative lesions over neck and chest. Lymphadenopathy and systemic involvement were absent. Patient was seronegative for HIV. There was no history of local injury and no history of travel. Histopathological findings were consistent with histoplasmosis. Diagnosis of primary cutaneous histoplasmosis was made. We highlight this case owing to its rare and atypical presentation, in an attempt to promote clinical and micro-pathological awareness regarding such occurrences.

Patterns of DNA methylation in individual colonic crypts reveal aging and cancer-related field defects in the morphologically normal mucosa.

Methylation of CpG islands (CGIs) in the promoter regions of tumour suppressor genes is common in colorectal cancer and occurs also in an age-dependent manner in the morphologically normal colorectal mucosa. In this study, we quantified the level of methylation of six genes associated with the Wnt signalling pathway (adenomatous polyposis coli, DKK1, WIF1, SFRP1, SFRP2 and SFRP5) together with long-interspersed nuclear element-1 as a surrogate for global methylation. DNA methylation was analysed in 260 individual colorectal crypts obtained from eight female patients with no evidence of colorectal disease and five with colorectal cancer. Significant variation in methylation levels for each of the six genes existed between crypts from the same biopsy. The variation in both global and gene-specific CGI methylation between crypts from the same individual was significantly less than that between individuals. Bisulphite sequencing provided insight into the mechanism of aberrant methylation showing that CGI methylation occurs in an 'all-or-none' manner by the directional spreading of methylation from further upstream. Univariate statistical analyses revealed that there were significant differences in crypt-specific methylation associated with both aging and disease status. A multivariate statistical modelling approach was able to distinguish both subject age and health status based on crypt-specific methylation profiles. Our results indicate that the differential methylation of genes associated with the Wnt signalling pathway affecting individual morphologically normal crypts may contribute to the age-dependent generation of the colonic field defect and, in combination with mutations, to the stepwise development of colorectal neoplasia.

Observer agreement in the angiographic assessment of arteriovenous malformations of the brain.

PURPOSE: We aimed to determine intraobserver and interobserver agreement in the characterization of brain arteriovenous malformation (AVM) angioarchitecture on intra-arterial digital subtraction angiograms. METHODS: Five experienced interventional neuroradiologists independently reviewed 40 anonymized angiograms obtained at the time of first-ever AVM diagnosis. The allocation of the films to observers was balanced for AVM size and complexity. Every observer was compared with himself and all the others by distributing the films in 2 batches 3 months apart. The observers used standard forms to collect both quantitative and categorized qualitative angiographic data. To measure agreement we used the kappa statistic (kappa) for nominal data, weighted kappa for ordinal and discrete interval data, and Bland & Altman analysis for continuous data. RESULTS: Intraobserver agreement was generally moderate to substantial, with 95% confidence intervals ranging from fair to almost perfect. However, for every characteristic, interobserver agreement was less than intraobserver agreement. Interobserver agreement was generally slight to moderate, with 95% confidence intervals ranging from less than chance to almost perfect. CONCLUSION: This study demonstrates the need for robust and generalizeable definitions of AVM angioarchitecture and methods of nidus size measurement-with proof of good intraobserver and interobserver agreement-for future efforts to understand the prognosis and best treatment of AVMs.