Chemosensory dysfunction as a marker of global disease: Investigating the role of taste and smell signalling in obesity and COVID-19

The work in this thesis examines chemosensory dysfunction related to obesity and COVID-19, two global pandemics markedly impacting on health. Following the COVID-19 outbreak, reports emerged that loss of smell and/or taste may be caused by SARS-CoV-2. The work in Chapter 2 was undertaken before loss of smell and/or taste were recognised COVID-19 symptoms and aimed to determine the seroprevalence of SARS-CoV-2 antibodies in people with acute taste and/or smell loss, characterise the loss of chemosensory function and identify factors affecting their recovery. Overall, 78% of people with taste and/or smell loss had positive SARS-CoV-2 IgG/IgM antibodies. Female sex and altered smell/taste perceptions were identified as predictors for persistent loss of sense of taste and/or smell and long COVID. Furthermore, objective smell testing and quantitative MRI brain imaging were undertaken to investigate the underlying pathophysiology. Early results suggest ongoing neuroinflammation in people with persistent smell loss. Obesity, a chronic disease with multiple associated co-morbidities, is associated with chemosensory dysfunction, particularly toward dietary fat. The obesity section of this thesis used different modalities, including functional taste assessment, salivary and circulating biomarkers and functional brain imaging to characterise chemosensory dysfunction in obesity. Findings from these studies demonstrated a reduced ability to taste fat in the fed state, as well as increased taste-stimulated activity in reward-related brain regions in people with obesity. Altered adipocytokines and inflammation are postulated to underlie the increased risk of critical illness from COVID-19 in people living with obesity. In Chapter 6 inflammatory adipocytokines and metabolomic markers were measured in people with obesity before and after bariatric surgery. A substantial inter-individual variability was identified in circulating levels of these markers, which may underlie some of the susceptibility to infection-induced critical illness. Importantly, the results indicated improvement in inflammation markers following bariatric surgery, suggesting the potential for reducing obesity-associated risks

Metabolic and Bariatric Endoscopy: A Mini-Review

We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty

Impact of sleeve gastrectomy compared to Roux-en-y gastric bypass upon hedonic hunger and the relationship to post-operative weight loss

'Hedonic hunger' indicates the desire to consume food in the absence of an energy requirement. Hedonic hunger can be investigated using the validated Power of Food Scale (PFS). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are currently the most effective treatment options for severe obesity. Following RYGB, hedonic hunger diminishes, which may contribute to sustained weight loss. There are no data examining the effect of SG on hedonic hunger. We prospectively evaluated hedonic hunger using PFS in patients with severe obesity prior to and 6 months after SG (n = 95) or RYGB (n = 44) and investigated the procedure-specific relationship between percentage weight loss (%WL) and hedonic hunger. Anthropometric data were collected at baseline after 6 months, 12 months and 24 months post-operatively. PFS contains 15 items grouped into 3 domains considering when food is: available (FA), present (FP), tasted (FT) and a total score (TS). At 6 months, a significant reduction was seen in all categories post-SG (p < 0.0001) and in TS (p = 0.003), FA (p = 0.0006) and FP (p = 0.0007) post-RYGB. A significantly larger reduction in FP scores was seen post-SG (p = 0.01). Post-SG, a significant correlation with 6-month %WL was noted for changes in FP (p = 0.03) and TS (p = 0.03). Post-SG changes in FP and TS predicted 24-month %WL. Post-RYGB significant correlations were seen between 6-month %WL and dFA (p = 0.04) and dFP (p = 0.03). Changes in FA, FP and TS were predictive of 12-month %WL. HH is reduced following both SG and RYGB with a greater reduction following SG and is related to post-operative %WL. PFS may have a role as a predictive tool for post-operative outcomes following SG and RYGB

Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management

Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

BACKGROUND: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. METHODS: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. FINDINGS: Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p < 0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p < 0.05, from whole brain statistical parametric map analysis). INTERPRETATION: This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies. FUNDING: This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case

Patients' views and experiences of a live supervised tele-exercise programme following bariatric surgery during the COVID-19 pandemic: the BARI-LIFESTYLE qualitative study

Funder: Rosetrees Trust; Id: http://dx.doi.org/10.13039/501100000833Funder: Sir Jules Thorn Trust Biomedical Research AwardFunder: University College London Overseas Research Scholarship (UCL‐ORS)Summary: The BARI‐LIFESTYLE trial is a randomized controlled trial evaluating the efficacy of a post‐surgery nutritional and behavioural tele‐counselling, and supervised exercise programme to maximize the health benefits of bariatric surgery. Due to the coronavirus disease 2019 (COVID‐19) pandemic, the in‐person supervised exercise component had to be converted to remote tele‐exercise. However, patients' acceptability of this method of exercise provision is unknown. Between 3 and 6 months following bariatric surgery, 13 adults participated in weekly, structured, 60‐min supervised exercise classes delivered via Zoom by a trained exercise therapist. A total of 12 participants (n = 8 female), with a mean age of 46.3 (range 33–63) years, who had undergone either sleeve gastrectomy (n = 8) or Roux‐en‐Y gastric bypass (n = 4) surgery, participated in one‐to‐one semi‐structured interviews following the tele‐exercise classes. Interviews were audio‐recorded, transcribed verbatim and analysed using thematic analysis. Participants described how the tele‐exercise classes helped them to cope with the changes to their lives brought about by the COVID‐19 pandemic. Participants found the tele‐exercise schedule, content and intensity to be acceptable, and were satisfied with the privacy, security and safety of the technology and classes. Professional supervision and guidance from an exercise therapist were described as central to the tele‐exercise provision. Importantly, participation in the tele‐exercise provided physical, emotional and social benefits. Few participants reported barriers to participation. Overall, the tele‐exercise classes were deemed acceptable and compared favourably to in‐person exercise classes

Obesity Management Task Force of the European Association for the Study of Obesity Released \u201cPractical Recommendations for the Post-Bariatric Surgery Medical Management\u201d

Bariatric patients may face specific clinical problems after surgery, and multidisciplinary long-term follow-up is usually provided in specialized centers. However, physicians, obstetricians, dieticians, nurses, clinical pharmacists, midwives, and physical therapists not specifically trained in bariatric medicine may encounter post-bariatric patients with specific problems in their professional activity. This creates a growing need for dissemination of first level knowledge in the management of bariatric patients. Therefore, the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO) decided to produce and disseminate a document containing practical recommendations for the management of post-bariatric patients. The list of practical recommendations included in the EASO/OMTF document is reported in this brief communication

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. Methods In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Findings Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p < 0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p < 0.05, from whole brain statistical parametric map analysis). Interpretation This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies