A protocol paper for the MOTION Study-A longitudinal study in a cohort aged 60 years and older to obtain mechanistic knowledge of the role of the gut microbiome during normal healthy ageing in order to develop strategies that will improve lifelong health and wellbeing.

BACKGROUND: Advances in medicine and public health mean that people are living longer; however, a significant proportion of that increased lifespan is spent in a prolonged state of declining health and wellbeing which places increasing pressure on medical, health and social services. There is a social and economic need to develop strategies to prevent or delay age-related disease and maintain lifelong health. Several studies have suggested links between the gut microbiome and age-related disease, which if confirmed would present a modifiable target for intervention development. The MOTION study aims to determine whether and how changes in the gut microbiome are associated with physical and mental capacity. A comprehensive longitudinal multiparameter study such as this has not been previously undertaken. METHODS: MOTION is a longitudinal prospective cohort study with a focus on gut health and cognitive function. 360 healthy individuals aged 60 years and older, living in East Anglia, UK will be recruited to the study, stratified into one of three risk groups (cohorts) for developing dementia based on their cognitive function. Participants will attend study appointments every six months over four years, providing stool and blood samples and a health questionnaire. Participants will also undergo physical measurements and cognitive tests at alternating appointments, and undergo Optical Coherence Tomography scans at 3 timepoints. Two subgroups of participants in the study will provide colonic tissue biopsies (n = ≥30 from each cohort), and brain imaging (n = 30) at two timepoints. DISCUSSION: This study will provide new insights into the gut-(microbiota)-brain axis and the relationship between age-associated changes in gut microbe populations and cognitive health. Such insights could help develop new microbe-based strategies to improve lifelong health and wellbeing. TRIAL REGISTRATION: This study is registered in the ClinicalTrials.gov Database with ID: NCT04199195 Registered: May 14, 2019.

Hand-Selective Visual Regions Represent How to Grasp 3D Tools: Brain Decoding during Real Actions.

Most neuroimaging experiments that investigate how tools and their actions are represented in the brain use visual paradigms where tools or hands are displayed as 2D images and no real movements are performed. These studies discovered selective visual responses in occipitotemporal and parietal cortices for viewing pictures of hands or tools, which are assumed to reflect action processing, but this has rarely been directly investigated. Here, we examined the responses of independently visually defined category-selective brain areas when participants grasped 3D tools (N = 20; 9 females). Using real-action fMRI and multivoxel pattern analysis, we found that grasp typicality representations (i.e., whether a tool is grasped appropriately for use) were decodable from hand-selective areas in occipitotemporal and parietal cortices, but not from tool-, object-, or body-selective areas, even if partially overlapping. Importantly, these effects were exclusive for actions with tools, but not for biomechanically matched actions with control nontools. In addition, grasp typicality decoding was significantly higher in hand than tool-selective parietal regions. Notably, grasp typicality representations were automatically evoked even when there was no requirement for tool use and participants were naive to object category (tool vs nontools). Finding a specificity for typical tool grasping in hand-selective, rather than tool-selective, regions challenges the long-standing assumption that activation for viewing tool images reflects sensorimotor processing linked to tool manipulation. Instead, our results show that typicality representations for tool grasping are automatically evoked in visual regions specialized for representing the human hand, the primary tool of the brain for interacting with the world.

Technical and Clinical Outcomes After Colorectal Stenting in Malignant Large Bowel Obstruction: A Single-Center Experience.

PURPOSE: Malignant large bowel obstruction is a surgical emergency that requires urgent decompression. Stents are increasingly being used, though reported outcomes are variable. We describe our multidisciplinary experience in using stents to manage malignant large bowel obstruction. METHODS: All patients undergoing colorectal stent insertion for acute large bowel obstruction in a teaching hospital were included. Outcomes, complications, and length of stay (LOS) were recorded. RESULTS: Over a 7-year period, 73 procedures were performed on 67 patients (37 male, mean age of 76 years). Interventional radiology was involved in all cases. Endoscopic guidance was required in 24 cases (32.9%). In 18 patients (26.9%), treatment intent was to bridge to elective surgery; 16 had successful stent placement; all had subsequent curative resection (laparoscopic resection, 8 of 18; primary anastomosis, 14 of 18). Overall LOS, including both index admission and elective admission, was 16.4 days. Treatment intent was palliative in 49 patients (73.1%). In this group, stents were successfully placed in 41 of 49 (83.7%). Complication rate within 30 days was 20%, including perforation (2 patients), per rectal bleeding (2), stent migration (1), and stent passage (5). Nineteen patients (38.8%) required subsequent stoma formation (6, during same admission; 13, during subsequent admission). Overall LOS was 16.9 days. CONCLUSION: In our experience colorectal stents can be used effectively to manage malignant large bowel obstruction, with only selective endoscopic input. As a bridge to surgery, most patients can avoid emergency surgery and have a primary anastomosis. In the palliative setting, the complication rate is acceptable and two-thirds avoid a permanent stoma.

Erdheim-Chester Disease: Two cases from an ophthalmic perspective.

PURPOSE: We report two patients who presented initially to ophthalmology clinics with symptoms and signs of orbital inflammation that led to a diagnosis of Erdheim-Chester Disease (ECD). OBSERVATIONS: ECD is a rare form of non-Langerhans cell histiocytosis (LCH) which is characterised by multi-system organ involvement and poor prognosis with standard therapies. Both patients were positive for the BRAF V600E mutation on genetic testing and were treated with the BRAF inhibitors Vemurafenib and Dabrafenib respectively. These cases highlight the variable clinical presentation and course of ECD, the classical radiological and histopathological findings, and the high degree of clinical suspicion necessary to reach this diagnosis. CONCLUSIONS AND IMPORTANCE: The combination of xanthelasma and bilateral, diffuse intraconal orbital masses must suggest to the clinician the possibility of ECD; and consideration to arrange further investigation with a full body CT or FDG PET/CT scan should be given, even in the absence of wider systemic symptoms or signs. With the advent of targeted therapies such as BRAF inhibitors, it is of even more importance that a diagnosis of ECD is established in a timely manner in order to give these patients the best chance of reduced morbidity and increased survival.

Pattern recognition is a sequential process-accurate diagnosis and treatment 20 years after presentation.

A 25-year-old woman presented with ophthalmic and neurological manifestations. Her ocular manifestations included bilateral uveitis, multifocal retinal phlebitis, vitreitis and multiple retinal haemorrhages. Her neurological manifestations included migrainous headaches with visual aura, transient sensory symptoms and posterior circulation Transient Ischemic Attack (TIA). Magnetic resonance imaging of the brain demonstrated lesions that involved the deep white matter lesions initially and progressed to also involve the juxta cortical white and deep grey matter and brain stem, but without further neurological manifestations. She was sequentially treated with intravenous and oral glucocorticoid, cyclophosphamide and mycophenolate mofetil, but she continued to suffer with persistent episodes of retinal haemorrhages. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), Susac syndrome and Behcet's disease were considered in the differential diagnosis. Genetic workup and clinical picture were not suggestive of the former two. Further history of oro-genital ulceration in younger age emerged, which pointed strongly towards a diagnosis of Behcet's disease with neurological involvement. She was treated with infliximab and methotrexate with complete resolution of her symptoms and withdrawal of corticosteroids for the first time in over two decades.

Spontaneous regression of a chiari malformation type 1 in a 58-year-old female.

Studies have established a complex age-related variation of the position of the cerebellar tonsils relative to the foramen magnum (FM). Chiari malformation type 1 (CM1) is generally defined by a protrusion >5 mm from the FM and may be an asymptomatic incidental finding. Symptoms include headache, nausea and neurological disturbances, including trigeminal neuralgia. Moreover, tonsils are often peg shaped and associated with syringohydromyelia. Symptomatic CM1 may be managed with decompression of the posterior cranial fossa, but spontaneous regression in adults has been reported occasionally. Theories include restoration of normal cerebrospinal fluid dynamics around the FM after rupture of subarachnoid adhesions or the syrinx itself during transient episodes of raised intracranial pressure. Supratentorial neurosurgery has also been implicated. We present a 58-year-old female diagnosed with CM1 and no associated syringohydromyelia following MRI investigation of trigeminal neuralgia. Managed medically, she re-presented 6 years later with new neurological symptoms. A subsequent MR study of the posterior cranial fossa showed resolution of the CM1, with only residual tonsillar ectopia. At no point was intracranial intervention performed, nor were there any events that might favour CM1 regression. This case demonstrates spontaneous resolution of CM1 without surgical intervention.

Collet-Sicard syndrome as a result of unilateral carotid artery dissection.

A 52-year-old man presented with sudden onset symptoms of multiple cranial nerve palsies (IX, X and XII) following a 10-day history of coryzal illness. Follow-up examination established atrophy of the trapezius suggesting additional involvement of the spinal accessory nerve (XI). Further investigation including CT and MRI demonstrated dissection of the internal carotid artery. Given the involvement of cranial nerves IX to XII, and that the patient demonstrated no signs of Horner's syndrome, we suggested that this patient fits the description of Collet-Sicard syndrome. On vascular opinion the carotid dissection was expected to resolve without intervention but the patient was prescribed aspirin for thromboprophylaxis. Gradual resolution of neurological symptoms was observed at 8-week follow-up.

Dementia is strongly associated with 90-day mortality in lobar cerebral amyloid angiopathy related intra-cerebral haemorrhage.

BACKGROUND: While evidence suggests that lobar intracerebral haemorrhage (ICH) is linked with dementia and cognitive impairment, the association between cognition and mortality risk from ICH is unclear. AIMS: To examine the association between dementia or cognitive impairment and short- and medium-term mortality post ICH. METHODS: Patients with primary ICH were classified into lobar and non-lobar ICH using radiological criteria. Patients' characteristics and radiological measures were collected at the baseline along with history of dementia and cognitive impairment. Mortality risks at 7, 30, 60, and 90 days were assessed using multiple logistic regression adjusting for potential confounders identified as significant associates in univariate models. RESULTS: A total of 136 patients (males 50%, mean age 77 years, SD 10) were included in this study. Out of 53 (39%) patients with lobar ICH 47 (89%) were classified as having possible and 6 (11%) as probable cerebral amyloid angiopathy (CAA). In lobar ICH the prevalence of history of dementia or cognitive impairment, confusion at presentation, previous ICH, multiple haemorrhages, and initial haematoma volume were significantly higher (p<0.05). In lobar ICH the significant mortality predictors (p<0.05) were history of dementia or cognitive impairment (90 days), prior antiplatelet use (60 and 90 days), initial haematoma volume (60 days), male sex (30 and 60 days), age (30, 60, 90 days), and low Glasgow Coma Scale (GCS) (7 and 30 days). In non-lobar ICH prior use of anticoagulation, initial haematoma volume, low GCS and age were significant mortality predictors (p<0.05). CONCLUSION: A history of dementia or cognitive impairment is more common in lobar CAA-related ICH and it is a medium-term mortality predictor in lobar ICH but not in deep non-lobar ICH.

One-stage tubeless antegrade ureteric stenting: a safe and cost-effective option?

INTRODUCTION: Antegrade insertion of ureteric stent has become an established mode of management of upper tract obstruction secondary to ureteric pathology. It is conventionally performed as a two-stage procedure for various reasons but, more recently, a one-stage approach has been adopted. PATIENTS AND METHODS: We discuss our experience of primary one-stage insertion of antegrade ureteric stent as a safe and cost-effective option for the management of these difficult cases in this retrospective observational case cohort study of patients referred to a radiology department for decompression of obstructed upper tracts. Data were retrieved from case notes and a radiology database for patients undergoing one-stage and two-stage antegrade stenting. It was followed by telephone survey of regional centres about the prevalent local practice for antegrade stenting. Outcome measures like hospital stay, procedural costs, requirement of analgesia/antimicrobials and complication rates were compared for the two approaches. RESULTS: a one-stage approach was found to be suitable in most cases with many advantages over the two-stage approach with comparable or better outcomes at lower costs. Some of the limitations of the study were retrospective data collection, more than one radiologist performing stenting procedures and non-availability of interventional radiologist falsely raising the incidence of two-stage procedures. CONCLUSIONS: In the absence of any clinical contra-indications and subject to availability of an interventional radiologist's support, one-stage antegrade stenting could easily be adopted as a routine approach for the management of benign or malignant ureteric obstruction.