Effect of combined GLP-1 analogue and bupropion/naltrexone on weight loss: a retrospective cohort study.

OBJECTIVE: Little is known about the effect of a multi-drug weight loss strategy in obesity treatment, particularly combining bupropion/naltrexone and glucagon-like peptide 1 (GLP-1) analogue. The purpose of this study was to evaluate if there are any additive effects of prescribing bupropion/naltrexone on top of GLP-1 analogue as weight loss therapy. METHODS: This was a retrospective cohort study of adult patients with a body mass index (BMI) ≥ 30 kg/m2 prescribed GLP-1 analogue therapy at an obesity specialist clinic in Vancouver, Canada. We compared a 6 and 12-month change in total body weight loss (TBWL) for those receiving monotherapy from the initiation of GLP-1 analogue therapy with those receiving combination therapy from the initiation of bupropion/naltrexone added-on therapy. Patients prescribed combination therapy were stratified into responder (loss of ≥ 5% TBWL) and non-responder (TBWL < 5%) subgroups based on initial response to the GLP-1 analogue alone for any amount of time. RESULTS: The mean weight loss among patients prescribed GLP-1 analogue monotherapy at 12 months was 11.42 kg, SD 9.95 (9.6% TBWL). There was no significant difference between these two treatment strategies overall (HR 0.88, 95% CI 0.68 to 1.14, p = 0.35). However, when stratified by response to initial GLP analogue therapy, the addition of bupropion/naltrexone was associated with a statistically significant reduction in weight in both the responder (4.3% TBWL (p < 0.01)) and non-responder groups (4.0% TBWL (p < 0.01)). CONCLUSIONS: GLP-1 analogues are an effective treatment for weight loss, and the addition of bupropion/naltrexone is associated with greater weight loss including in patients who are initially non-responsive to GLP-1 analogues.

Image quality in whole-body MRI using the MY-RADS protocol in a prospective multi-centre multiple myeloma study.

BACKGROUND: The Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines establish a standardised acquisition and analysis pipeline for whole-body MRI (WB-MRI) in patients with myeloma. This is the first study to assess image quality in a multi-centre prospective trial using MY-RADS. METHODS: The cohort consisted of 121 examinations acquired across ten sites with a range of prior WB-MRI experience, three scanner manufacturers and two field strengths. Image quality was evaluated qualitatively by a radiologist and quantitatively using a semi-automated pipeline to quantify common artefacts and image quality issues. The intra- and inter-rater repeatability of qualitative and quantitative scoring was also assessed. RESULTS: Qualitative radiological scoring found that the image quality was generally good, with 94% of examinations rated as good or excellent and only one examination rated as non-diagnostic. There was a significant correlation between radiological and quantitative scoring for most measures, and intra- and inter-rater repeatability were generally good. When the quality of an overall examination was low, this was often due to low quality diffusion-weighted imaging (DWI), where signal to noise ratio (SNR), anterior thoracic signal loss and brain geometric distortion were found as significant predictors of examination quality. CONCLUSIONS: It is possible to successfully deliver a multi-centre WB-MRI study using the MY-RADS protocol involving scanners with a range of manufacturers, models and field strengths. Quantitative measures of image quality were developed and shown to be significantly correlated with radiological assessment. The SNR of DW images was identified as a significant factor affecting overall examination quality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03188172 , Registered on 15 June 2017. CRITICAL RELEVANCE STATEMENT: Good overall image quality, assessed both qualitatively and quantitatively, can be achieved in a multi-centre whole-body MRI study using the MY-RADS guidelines. KEY POINTS: • A prospective multi-centre WB-MRI study using MY-RADS can be successfully delivered. • Quantitative image quality metrics were developed and correlated with radiological assessment. • SNR in DWI was identified as a significant predictor of quality, allowing for rapid quality adjustment.

Methylation of histone H3 lysine 4 is required for maintenance of beta cell function in adult mice.

AIMS/HYPOTHESIS: Beta cells control glucose homeostasis via regulated production and secretion of insulin. This function arises from a highly specialised gene expression programme that is established during development and then sustained, with limited flexibility, in terminally differentiated cells. Dysregulation of this programme is seen in type 2 diabetes but mechanisms that preserve gene expression or underlie its dysregulation in mature cells are not well resolved. This study investigated whether methylation of histone H3 lysine 4 (H3K4), a marker of gene promoters with unresolved functional importance, is necessary for the maintenance of mature beta cell function. METHODS: Beta cell function, gene expression and chromatin modifications were analysed in conditional Dpy30 knockout mice, in which H3K4 methyltransferase activity is impaired, and in a mouse model of diabetes. RESULTS: H3K4 methylation maintains expression of genes that are important for insulin biosynthesis and glucose responsiveness. Deficient methylation of H3K4 leads to a less active and more repressed epigenome profile that locally correlates with gene expression deficits but does not globally reduce gene expression. Instead, developmentally regulated genes and genes in weakly active or suppressed states particularly rely on H3K4 methylation. We further show that H3K4 trimethylation (H3K4me3) is reorganised in islets from the Leprdb/db mouse model of diabetes in favour of weakly active and disallowed genes at the expense of terminal beta cell markers with broad H3K4me3 peaks. CONCLUSIONS/INTERPRETATION: Sustained methylation of H3K4 is critical for the maintenance of beta cell function. Redistribution of H3K4me3 is linked to gene expression changes that are implicated in diabetes pathology.

Prospective comparison of magnetic resonance imaging and computed tomography in diagnosing occult scaphoid fractures.

BACKGROUND: Suspected scaphoid fracture (SF) after a fall on an outstretched hand is a common presentation in the emergency department. Magnetic resonance imaging (MRI) or computed tomography (CT) has been suggested to assist in the diagnosis or exclusion of SF. PURPOSE: To compare MRI and CT at diagnosing occult SFs. MATERIAL AND METHODS: We routinely perform CT scans in patients with clinically suspected occult SF, after 7-10 days of injury following two negative radiographs. All eligible patients with a clinically suspected SF, but negative radiographs and a negative CT, underwent an MRI scan to assess further for evidence of occult fracture. RESULTS: A total of 100 patients were included in our study. MRI showed fractures in 16% of the time (in 15 patients) when plain radiographs and CT did not. Of these fractures, 8% were SFs. In addition to fractures, 10% had bone bruising. A total of 25% of patients with fractures and bone bruising were referred to the hand surgery team for further follow-up. CONCLUSION: The study demonstrated that MRI would identify a radiographically occult SF more often than CT. This supports NICE guidelines which recommend MRI as the best early diagnostic tool for occult SFs.

Implementation of Whole-Body MRI (MY-RADS) within the OPTIMUM/MUKnine multi-centre clinical trial for patients with myeloma.

BACKGROUND: Whole-body (WB) MRI, which includes diffusion-weighted imaging (DWI) and T1-w Dixon, permits sensitive detection of marrow disease in addition to qualitative and quantitative measurements of disease and response to treatment of bone marrow. We report on the first study to embed standardised WB-MRI within a prospective, multi-centre myeloma clinical trial (IMAGIMM trial, sub-study of OPTIMUM/MUKnine) to explore the use of WB-MRI to detect minimal residual disease after treatment. METHODS: The standardised MY-RADS WB-MRI protocol was set up on a local 1.5 T scanner. An imaging manual describing the MR protocol, quality assurance/control procedures and data transfer was produced and provided to sites. For non-identical scanners (different vendor or magnet strength), site visits from our physics team were organised to support protocol optimisation. The site qualification process included review of phantom and volunteer data acquired at each site and a teleconference to brief the multidisciplinary team. Image quality of initial patients at each site was assessed. RESULTS: WB-MRI was successfully set up at 12 UK sites involving 3 vendor systems and two field strengths. Four main protocols (1.5 T Siemens, 3 T Siemens, 1.5 T Philips and 3 T GE scanners) were generated. Scanner limitations (hardware and software) and scanning time constraint required protocol modifications for 4 sites. Nevertheless, shared methodology and imaging protocols enabled other centres to obtain images suitable for qualitative and quantitative analysis. CONCLUSIONS: Standardised WB-MRI protocols can be implemented and supported in prospective multi-centre clinical trials. Trial registration NCT03188172 clinicaltrials.gov; registration date 15th June 2017 https://clinicaltrials.gov/ct2/show/study/NCT03188172.

MRI findings seen in serous atrophy of bone marrow.

An 85-year-old man was referred for an MRI scan of the pelvis for further evaluation of a suspected left neck of femur fracture, which was regarded as equivocal on plain radiograph and CT. The initial MRI demonstrated unusual appearances of the visualised bone marrow and subcutaneous adipose tissue and was initially misinterpreted as a technical malfunction of the scanner. However, a repeat study on a different scanner the following day once again demonstrated the same appearances. The appearances were consistent with serous atrophy of bone marrow, a non-neoplastic disorder of the bone marrow, which is most commonly seen in severe anorexia nervosa or cachexia. These unusual, but distinct, bone marrow and subcutaneous adipose tissue appearances, which are specific to MRI, have been colloquially termed as the 'flip-flop' effect.

Split and partially entwined sciatic nerve following closed reduction of a dislocated hip prosthesis.

We present a case of split and partially entwined sciatic nerve by a femoral prosthesis following closed reduction of a dislocated hip replacement. This complication is very rare and there are only few cases reported in the literature, with even less accompanied by supporting MRI. We present MRI features of a split and partially entwined sciatic nerve around a hip prosthesis.

Twinkle artefact in the ultrasound diagnosis of superficial epidermoid cysts.

AIM: The aim of the study was to evaluate whether the twinkle artefact is a valuable feature in the sonographic diagnosis of superficial epidermoid cysts. MATERIALS AND METHODS: A retrospective search was undertaken of our institution's Radiology Information System and pathology database to identify cases of superficial masses showing the twinkle artefact that proceeded to surgical excision. RESULTS: Eighteen superficial masses demonstrating the twinkle artefact were identified that were submitted for pathological analysis. Of these, 17 were confirmed to represent epidermoid cysts and only 1 case had an alternative diagnosis (proliferating trichilemmal cyst). CONCLUSION: The presence of the twinkle artefact appears to be a specific and valuable ancillary sonographic feature for the diagnosis of superficial epidermoid cysts.

Sarcoidosis--the greatest mimic.

Little is known regarding the exact pathogenesis of sarcoidosis, but it is widely recognized that it affects multiple organs. The presentation and imaging features can be nonspecific, and this is the reason why it is a great mimic of other diseases. Diagnosis of sarcoidosis is often prompted initially by clinical suspicion. Imaging plays a crucial role in both detection and monitoring of disease process. This review is a case-based systemic approach looking at various systemic manifestation of the disease presenting real clinical encounters using various imaging modalities.

Comprehensive musculoskeletal sonographic evaluation of the hand and wrist.

Sonography is widely used for evaluation of hand and wrist lesions. The easy accessibility, cost-effectiveness, and good diagnostic accuracy of sonography coupled with the numerous benefits of real-time imaging make it desirable. The aim of this article is to describe the typical sonographic appearances of lesions in the hand and wrist that are encountered frequently in routine clinical practice, such as inflammatory arthropathies, tumors, traumatic injuries, foreign bodies, and nerve entrapment syndromes. Relevant anatomy, scanning methods, and recent developments in musculoskeletal sonography are also discussed.

Usual and unusual causes of splaying of the carotid artery bifurcation: the Lyre sign--a pictorial review.

The 'Lyre' sign describes the characteristic splaying of the carotid artery bifurcation due to a carotid body tumour (paraganglioma) on conventional carotid angiography. In this pictorial review, we describe and illustrate two cases demonstrating the equivalent Lyre sign on multi-detector computed tomography (MDCT) and ultrasound resulting from carotid body tumour and extra-cranial internal carotid artery pseudoaneurysm. Both of these pathologies can manifest acutely and warrant accurate diagnosis to prevent potential catastrophic consequences. We also emphasise the added value of MDCT in making a definitive diagnosis and discuss other differential considerations splaying the carotid bifurcation.

Subtrochanteric femoral insufficiency fractures related to the use of long-term bisphosphonates: a pictorial review.

Sub-trochanteric femoral fractures as a complication of long standing bisphosphonate therapy are rare. Drug regulatory authorities like MHRA in the UK (Medicines and Healthcare products Regulatory Agency) have recently alerted specialists about this complication. We describe and illustrate the plain radiographic, CT and MRI features and emphasize the role of imaging in the accurate diagnosis of this new type of insufficiency fractures. There is paucity of radiology literature on this topic and hence awareness of the typical imaging features helps to prevent misdiagnosis and delayed treatment. Our patients were on bisphosphonates (alendronate) for more than 3 years duration and presented with anterolateral thigh pain to the emergency department.