57 research outputs found
Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview
C.R.C. was funded by the Derek Willoughby Fund for Inflammatory Research. A.L.H. and T.A.G. were funded by Higher Education Funding Council of England
Bariatric-metabolic surgery for NHS patients with type 2 diabetes in the United Kingdom National Bariatric Surgery Registry
Aim: Bariatric-metabolic surgery is approved by the National Institute of Health and Care Excellence (NICE) for people with severe obesity and type 2 diabetes (T2DM) (including class 1 obesity after 2014). This study analysed baseline characteristics, disease severity and operations undertaken in people with obesity and T2DM undergoing bariatric-metabolic surgery in the UK National Health Service (NHS) compared to those without T2DM. Methods: Baseline characteristics, trends over time and operations undertaken were analysed for people undergoing primary bariatric-metabolic surgery in the NHS using the National Bariatric Surgical Registry (NBSR) for 11 years from 2009 to 2019. Clinical practice before and after the publication of the NICE guidance (2014) was examined. Multivariate logistic regression was used to determine associations with T2DM status and the procedure undertaken. Results: 14,948/51,715 (28.9%) participants had T2DM, with 10,626 (71.1%) on oral hypoglycaemics, 4322 (28.9%) on insulin/other injectables, and with T2DM diagnosed 10+ years before surgery in 3876 (25.9%). Participants with T2DM, compared to those without T2DM, were associated with older age (p < 0.001), male sex (p < 0.001), poorer functional status (p < 0.001), dyslipidaemia (OR: 3.58 (CI: 3.39–3.79); p < 0.001), hypertension (OR: 2.32 (2.19–2.45); p < 0.001) and liver disease (OR: 1.73 (1.58–1.90); p < 0.001), but no difference in body mass index was noted. Fewer people receiving bariatric-metabolic surgery after 2015 had T2DM (p < 0.001), although a very small percentage increase of those with class I obesity and T2DM was noted. Gastric bypass was the commonest operation overall. T2DM status was associated with selection for gastric bypass compared to sleeve gastrectomy (p < 0.001). Conclusion: NHS bariatric-metabolic surgery is used for people with T2DM much later in the disease process when it is less effective. National guidance on bariatric-metabolic surgery and data from multiple RCTs have had little impact on clinical practice.</p
Low-Grade Dysplasia in Ulcerative Colitis: Risk Factors for Developing High-Grade Dysplasia or Colorectal Cancer
Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility
Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes
Influence of zinc on glycosaminoglycan neutralisation during coagulation
This work was supported by the British Heart Foundation (grant codes: PG/15/9/31270 and FS/15/42/31556). SJP is supported by a Royal Society of Edinburgh Biomedical Fellowship.Heparan sulfate (HS), dermatan sulfate (DS) and heparin are glycosaminoglycans (GAGs) that serve as key natural and pharmacological anticoagulants. During normal clotting such agents require to be inactivated or neutralised. Several proteins have been reported to facilitate their neutralisation, which reside in platelet α-granules and are released following platelet activation. These include histidine-rich-glycoprotein (HRG), fibrinogen and high-molecular-weight kininogen (HMWK). Zinc ions (Zn2+) are also present in α-granules at a high concentration and participate in the propagation of coagulation by influencing the binding of neutralising proteins to GAGs. Zn2+ in many cases increases the affinity of these proteins to GAGs, and is thus an important regulator of GAG neutralisation and haemostasis. Binding of Zn2+ to HRG, HMWK and fibrinogen is mediated predominantly through coordination to histidine residues but the mechanisms by which Zn2+ increases the affinity of the proteins for GAGs are not yet completely clear. Here we will review current knowledge of how Zn2+ binds to and influences the neutralisation of GAGs and describe the importance of this process in both normal and pathogenic clotting.Publisher PDFPeer reviewe
Investigating patient groups at risk of poor outcome in colorectal cancer
This thesis examines colorectal cancer (CRC) outcomes in England including re-operation, perioperative mortality and survival. The aim of this thesis has been to explore the patient, presentation mode (emergency or elective), tumour biology and healthcare provision factors that contribute to poor outcome (perioperative morbidity and mortality, reduced survival) in CRC patients in England.
Several methodologies have been used to answer the relevant scientific questions, including local (hospital) clinical data, screening data, systematic reviews and meta analyses, regional cancer datasets as well as national administrative datasets. This thesis has demonstrated that a variety of socioeconomic, disease and presentation factors contribute to poor outcome including ethnicity (Black Afro-Caribbean patients), social deprivation and patients undergoing emergency resection for their CRC. Similarly, patients with Inflammatory Bowel Disease (IBD) and cancer are more likely to require immediate perioperative re-intervention and re-operation than those without IBD. They also tend to have a worse overall survival.
The way healthcare is delivered to patients with CRC can also have an impact on outcomes. Patients selected to undergo laparoscopic resection for CRC had fewer complications, and in the long-term their survival was better than patients undergoing open procedures. The use of new minimal access surgery as well as better care may be the drivers behind improving outcomes in England. There appears to be a wide variation in the patients we offer surgery to. In the elderly group (over 80 years of age), the variability in the percentage of elderly patients undergoing surgery in different units was significant (ranging from 6.2% to 83.3%).
To improve outcomes nationally, it is vital that we strengthen targeted measures such as population screening, obtain better control of diseases contributing to CRC (such as IBD) and develop a standardised selection process in choosing the patients that would benefit the most from surgery.Open Acces
National Introduction of One Anastomosis Gastric Bypass in the United Kingdom National Bariatric Surgery Registry
A study to evaluate the efficacy and safety of introduction of the one-anastomosis gastric bypass into clinical practice in the United Kingdom National Bariatric Surgery Registr
Metastatic Involvement of The Omentum In Patients Undergoing Oesophagectomy: A Multi-Centre Study
Appraisal of the current guidelines for management of cholangiocarcinoma-using the Appraisal of Guidelines Research and Evaluation II (AGREE II) Instrument.
Cholangiocarcinoma (CC) is the second most common primary liver tumour. High-quality guidelines are essential for effective patient stratification and individualised treatment. This study aimed to appraise the methodological quality of existing guidelines for the resection of CC using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. A systematic search of the literature in Cochrane, PubMed, Google Scholar, and Embase was performed. Assessment of the clinical practice guidelines (CPGs) and consensuses was performed using the AGREE II instrument by four clinicians experienced in surgical practice and the AGREE II appraisal method. Literature searches identified 13 guidelines of highly variable quality according to the AGREE II criteria. The guidelines scored well in certain domains such as scope & purpose (median score across all guidelines; 65%), clarity of presentation (76%), and editorial independence (56%). However, they scored poorly for applicability (13%), rigour of development (30%), and stakeholder involvement (39%). None of the 13 guidelines was recommended universally for use without modification. Overall, the methodological quality of guidelines on the surgical management of CC is poor. Future updates should address and modify shortcomings detected by the AGREE II instrument, thereby facilitating better patient stratification and individualised treatment strategies
- …