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1.
Gut ; 73(8): 1235-1268, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38627031

ABSTRACT

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/therapy , Liver Neoplasms/diagnosis , United Kingdom , Adult , Gastroenterology/standards , Liver Transplantation , Chemoembolization, Therapeutic
2.
Emerg Med J ; 41(3): 153-161, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38050049

ABSTRACT

BACKGROUND: Standardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres. METHODS: Consensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines. A national patient charity for aortic dissection was involved in the design of the Delphi study. Vascular and cardiothoracic surgeons, emergency physicians, interventional radiologists, cardiologists, intensivists and anaesthetists in the United Kingdom were invited to participate via their respective professional societies. RESULTS: Three consecutive rounds of an electronic Delphi survey were completed by 212, 101 and 58 respondents, respectively. Using predefined consensus criteria, 60 out of 117 (51%) statements from the survey were included in the consensus statement. The study concluded that patients can be taken directly to a specialist aortic centre if they have typical symptoms of AAS on the background of known aortic disease or previous aortic intervention. Accepted patients should be transferred in a category 2 ambulance (response time <18 min), ideally accompanied by transfer-trained personnel or Adult Critical Care Transfer Services. A clear plan should be agreed in case of a cardiac arrest occurring during the transfer. Patients should reach the aortic centre within 4 hours of the initial referral from their local hospital. CONCLUSIONS: This consensus statement is the first set of national interdisciplinary recommendations on the interhospital transfer of patients with AAS. Its implementation is likely to contribute to safer and more standardised emergency referral pathways to regional high-volume specialist aortic units.


Subject(s)
Aortic Dissection , Adult , Humans , Delphi Technique , Aortic Dissection/therapy , Referral and Consultation , United Kingdom , England
3.
BMJ Open ; 13(3): e064739, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36878659

ABSTRACT

OBJECTIVES: There is emerging use of artificial intelligence (AI) models to aid diagnostic imaging. This review examined and critically appraised the application of AI models to identify surgical pathology from radiological images of the abdominopelvic cavity, to identify current limitations and inform future research. DESIGN: Systematic review. DATA SOURCES: Systematic database searches (Medline, EMBASE, Cochrane Central Register of Controlled Trials) were performed. Date limitations (January 2012 to July 2021) were applied. ELIGIBILITY CRITERIA: Primary research studies were considered for eligibility using the PIRT (participants, index test(s), reference standard and target condition) framework. Only publications in the English language were eligible for inclusion in the review. DATA EXTRACTION AND SYNTHESIS: Study characteristics, descriptions of AI models and outcomes assessing diagnostic performance were extracted by independent reviewers. A narrative synthesis was performed in accordance with the Synthesis Without Meta-analysis guidelines. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)). RESULTS: Fifteen retrospective studies were included. Studies were diverse in surgical specialty, the intention of the AI applications and the models used. AI training and test sets comprised a median of 130 (range: 5-2440) and 37 (range: 10-1045) patients, respectively. Diagnostic performance of models varied (range: 70%-95% sensitivity, 53%-98% specificity). Only four studies compared the AI model with human performance. Reporting of studies was unstandardised and often lacking in detail. Most studies (n=14) were judged as having overall high risk of bias with concerns regarding applicability. CONCLUSIONS: AI application in this field is diverse. Adherence to reporting guidelines is warranted. With finite healthcare resources, future endeavours may benefit from targeting areas where radiological expertise is in high demand to provide greater efficiency in clinical care. Translation to clinical practice and adoption of a multidisciplinary approach should be of high priority. PROSPERO REGISTRATION NUMBER: CRD42021237249.


Subject(s)
Pathology, Surgical , Humans , Artificial Intelligence , Cross-Sectional Studies , Retrospective Studies , Radiography
5.
Breast ; 66: 69-76, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36194950

ABSTRACT

BACKGROUND: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. PATIENTS AND METHODS: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). RESULTS: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. CONCLUSIONS: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.


Subject(s)
Breast Neoplasms , Neutropenia , Humans , Female , Breast Neoplasms/pathology , Paclitaxel , Quality of Life , Receptor, ErbB-2 , Neutropenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Treatment Outcome
6.
BMJ Open ; 11(10): e054411, 2021 10 20.
Article in English | MEDLINE | ID: mdl-34670769

ABSTRACT

INTRODUCTION: The application of artificial intelligence (AI) technologies as a diagnostic aid in healthcare is increasing. Benefits include applications to improve health systems, such as rapid and accurate interpretation of medical images. This may improve the performance of diagnostic, prognostic and management decisions. While a large amount of work has been undertaken discussing the role of AI little is understood regarding the performance of such applications in the clinical setting. This systematic review aims to critically appraise the diagnostic performance of AI algorithms to identify disease from cross-sectional radiological images of the abdominopelvic cavity, to identify current limitations and inform future research. METHODS AND ANALYSIS: A systematic search will be conducted on Medline, EMBASE and the Cochrane Central Register of Controlled Trials to identify relevant studies. Primary studies where AI-based technologies have been used as a diagnostic aid in cross-sectional radiological images of the abdominopelvic cavity will be included. Diagnostic accuracy of AI models, including reported sensitivity, specificity, predictive values, likelihood ratios and the area under the receiver operating characteristic curve will be examined and compared with standard practice. Risk of bias of included studies will be assessed using the QUADAS-2 tool. Findings will be reported according to the Synthesis Without Meta-analysis guidelines. ETHICS AND DISSEMINATION: No ethical approval is required as primary data will not be collected. The results will inform further research studies in this field. Findings will be disseminated at relevant conferences, on social media and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021237249.


Subject(s)
Artificial Intelligence , Diagnostic Imaging , Bias , Cross-Sectional Studies , Humans , Radiography , Systematic Reviews as Topic
7.
Colorectal Dis ; 23(7): 1900-1908, 2021 07.
Article in English | MEDLINE | ID: mdl-33686656

ABSTRACT

AIM: Abdominal surgery sometimes necessitates the creation of a stoma, which can cause future complications including parastomal hernia (PSH), an incisional hernia adjacent to and related to the stoma. PSH affects approximately 40% of patients within 2 years of stoma formation. Complications of PSH reduce a patient's quality of life and can be severe (e.g. bowel obstruction). PSHs are difficult to manage and can recur after surgical repair. Therefore, it is very important to prevent a PSH. Surgeons create stomas in different ways and both patient and surgical factors are believed to influence the development of PSH. The aim of the CIPHER study is to investigate the influence of different surgical techniques on the development of PSH. METHOD: The UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study) aims to recruit 4000 patients undergoing elective or expedited surgery with the intention of forming an ileostomy or colostomy, irrespective of the primary indication for the planned surgery. For each patient, surgeons will describe their methods of trephine formation, mesh reinforcement of the stoma trephine, use of the stoma as a specimen extraction site and wound closure. The primary outcome will be incident PSH during follow-up, defined as symptoms of PSH (custom-designed questionnaire) and anatomical PSH, ascertained by independent reading of usual care CT scans. Secondary outcomes will include surgical site infection, the Comprehensive Complication Index, quality of life (EQ-5D-5L and SF-12), PSH repair and use of NHS resources. RESULTS: Results of the study will be submitted for publication in peer-reviewed journals. All publications relating to the results of CIPHER will use a corporate authorship, 'The CIPHER Study Investigators' with named writing committee members. CONCLUSION: The CIPHER study will be the first to investigate detailed surgical methods of stoma formation in a large, representative cohort of patients with a range of primary indications, both cancer and noncancer.


Subject(s)
Hernia, Ventral , Incisional Hernia , Surgical Stomas , Cohort Studies , Colostomy , Hernia, Ventral/etiology , Hernia, Ventral/surgery , Humans , Incisional Hernia/etiology , Incisional Hernia/prevention & control , Neoplasm Recurrence, Local , Quality of Life , Surgical Mesh , Surgical Stomas/adverse effects , United Kingdom
8.
Pancreatology ; 18(8): 962-970, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30292643

ABSTRACT

To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.


Subject(s)
Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Adult , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Guidelines as Topic , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Positron-Emission Tomography , United Kingdom
9.
Br J Hosp Med (Lond) ; 78(6): 320-326, 2017 Jun 02.
Article in English | MEDLINE | ID: mdl-28614024

ABSTRACT

Aortic dissection remains a serious cardiovascular emergency with significant early and late mortality and morbidity. Improving outcomes is directly linked to early clinical diagnosis, swift confirmation by appropriate imaging and management by dedicated teams with high levels of expertise in a complex clinical condition.


Subject(s)
Antihypertensive Agents/therapeutic use , Aortic Aneurysm/therapy , Aortic Dissection/diagnostic imaging , Aortic Dissection/therapy , Pain Management/methods , Vascular Surgical Procedures/methods , Aortic Dissection/complications , Aortic Aneurysm/complications , Aortic Aneurysm/diagnostic imaging , Aortic Rupture/etiology , Early Diagnosis , Early Medical Intervention , Echocardiography , Emergencies , Humans , Magnetic Resonance Imaging , Tomography, X-Ray Computed
10.
J Clin Endocrinol Metab ; 101(12): 4661-4668, 2016 12.
Article in English | MEDLINE | ID: mdl-27648968

ABSTRACT

CONTEXT: Maternal adiposity in pregnancy is associated with offspring adiposity and metabolic dysfunction postnatally, including greater risk of nonalcoholic fatty liver disease (NAFLD). Recent genetic analyses suggest a causal effect of greater maternal body mass index on offspring birth weight and ponderal index, but the relative roles of the environment in utero or later in life remains unclear. OBJECTIVE: We sought to determine whether markers of infant adiposity (birth weight, umbilical cord blood leptin, adiponectin, and lipids) were associated with markers of NAFLD in adolescence. DESIGN, SETTING, AND PARTICIPANTS: This was a UK prospective birth cohort with 17 years of follow-up with liver function tests (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase) (n = 1037 participants), and ultrasound scan assessed liver fat, volume, and sheer velocity at age 17 (n = 541 participants). Missing covariate data were imputed. MAIN OUTCOMES: Ultrasound and biochemical measures of NAFLD were measured. RESULTS: Birth weight, cord blood leptin, and adiponectin were not associated with a diagnosis of NAFLD. In adjusted analyses, 2 of 42 associations attained conventional 5% levels of significance. Birth weight was positively associated with liver volume (1.0% greater per 100 g [95% confidence interval 0.5%-2.0%]). Cord high-density lipoprotein-cholesterol was positively associated with alanine aminotransferase (11.6% higher per 1 mmol/L [95% confidence interval 0.3, 23.4]); however, this association was primarily mediated via offspring adiposity. CONCLUSIONS: In this extensive analysis, we found little evidence measurements of infant fat mass and birth size were related to adolescent markers of NAFLD. The association between birth weight and adolescent liver volume may indicate the contribution of greater organ size to birth weight and tracking of organ size.


Subject(s)
Adipokines/metabolism , Adiposity , Alanine Transaminase/metabolism , Birth Weight , Cholesterol, HDL/metabolism , Fetal Blood/metabolism , Non-alcoholic Fatty Liver Disease/diagnosis , Adolescent , Female , Follow-Up Studies , Humans , Infant, Newborn , Male , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/metabolism , Pregnancy
11.
BMC Pediatr ; 16: 47, 2016 Mar 31.
Article in English | MEDLINE | ID: mdl-27036545

ABSTRACT

BACKGROUND: Little is known about early life determinants of non-alcoholic fatty liver disease (NAFLD). We examined associations of maternal pregnancy diabetes/glycosuria and pre-pregnancy body mass index (BMI) with offspring markers of NAFLD and liver pathology and examined mediation by birthweight and concurrent offspring adiposity. METHODS: We used data from a UK prospective pregnancy cohort. Offspring underwent abdominal ultrasonography (USS) at mean age 17.8 years. Outcomes included USS-assessed fatty liver, estimated liver volume and shear velocity, a variant of elastography (a marker of liver fibrosis) (N = 1 215) and blood-based markers of liver pathology [alanine amino transferase, aspartate amino transferase, gamma- glutamyltransferase and haptoglobin] (N = 2 359). RESULTS: 2.1 % (N = 25) of participants had USS-assessed fatty liver [maternal diabetes/glycosuria (N = 7) and no diabetes/glycosuria (N = 18)]. Maternal diabetes/glycosuria was associated with greater odds of offspring USS fatty liver in confounder adjusted models [adjusted odds ratio (aOR) 6.74 (95 % confidence interval (CI) 2.47, 18.40)] and higher shear velocity [adjusted ratio of geometric mean (aRGM):1.10 (95 % CI 1.05, 1.15)]. These associations were not mediated by offspring birthweight or concurrent adiposity. Maternal diabetes/glycosuria was not associated with liver volume or blood-based outcomes. Greater maternal pre-pregnancy BMI was associated with greater odds of offspring USS fatty liver [aOR 2.72 (95 % CI: 1.20, 6.15)], higher liver volume [aRGM 1.03 (95 % CI 1.00, 1.07)] and shear velocity [aRGM1.03 (95 % CI: 1.01, 1.06)] in confounder adjusted models. These associations were largely mediated by offspring adiposity. Maternal pre-pregnancy BMI was not consistently associated with blood-based outcomes. CONCLUSIONS: Results suggest that maternal pregnancy diabetes/glycosuria is associated with offspring NAFLD through mechanisms other than offspring's own adiposity.


Subject(s)
Body Mass Index , Glycosuria , Non-alcoholic Fatty Liver Disease/etiology , Pregnancy in Diabetics , Prenatal Exposure Delayed Effects/etiology , Adiposity , Adolescent , Birth Weight , Female , Humans , Longitudinal Studies , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Odds Ratio , Pregnancy , Pregnancy Complications , Prenatal Exposure Delayed Effects/diagnosis , Prospective Studies , Risk Factors
12.
J Pediatr Gastroenterol Nutr ; 62(1): 110-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26252921

ABSTRACT

OBJECTIVES: The aim of the present study was to assess whether objectively measured physical activity at mean ages 12 and 14 years are prospectively associated with ultrasound scan liver fat and stiffness (alanine aminotransferase, aspartate aminotransferase [AST], and γ-glutamyl transferase [GGT]) assessed at mean age 17.8 years. METHODS: Participants were from the Avon Longitudinal Study of Parents and Children. Total physical activity (counts per minute) and minutes of moderate to vigorous physical activity (MVPA) were measured using ActiGraph accelerometers at mean ages 12 and 14 years. RESULTS: Greater total physical activity and MVPA at ages 12 and 14 years were associated with lower odds of liver fat and lower GGT levels at mean age 17.8 years, such as per 15-minute increase in daily MVPA at age 12 years, the confounder adjusted odds ratio of liver fat was 0.47 (95% confidence interval [CI] 0.27-0.84). Associations attenuated after additional adjustment for fat mass as a potential confounder (eg, per 15-minute increase in daily MVPA at age 12 years, the odds ratio of liver fat attenuated to 0.65 [95% CI 0.35-1.21]) or a potential mediator (eg, per 15-minute increase in daily MVPA at age 12 years the odds ratio of liver fat attenuated to 0.59 [95% CI 0.32-1.09]). Results did not further attenuate after additional adjustment for insulin resistance. There was some evidence that greater total physical activity and MVPA at age 12 years were associated with the higher AST levels. CONCLUSIONS: Adolescents who were more active in childhood have lower odds of fatty liver and lower GGT levels. These findings are likely to be, at least in part, explained by adiposity.


Subject(s)
Liver/physiopathology , Motor Activity/physiology , Non-alcoholic Fatty Liver Disease/physiopathology , Adiposity , Adolescent , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Child , Female , Humans , Liver/diagnostic imaging , Liver/enzymology , Liver Function Tests , Longitudinal Studies , Male , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/etiology , Odds Ratio , Prospective Studies , Risk Factors , Ultrasonography , gamma-Glutamyltransferase/blood
13.
J Nutr ; 145(5): 983-9, 2015 May.
Article in English | MEDLINE | ID: mdl-25788585

ABSTRACT

BACKGROUND: Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus, it is likely that dietary intake is involved in the development of the disease. Prospective studies assessing the relation between childhood dietary intake and risk of NAFLD are lacking. OBJECTIVE: This study was designed to explore associations between energy, carbohydrate, sugar, starch, protein, monounsaturated fat, polyunsaturated fat, saturated fat, and total fat intake by youth at ages 3, 7, and 13 y and subsequent (mean age: 17.8 y) ultrasound scan (USS)-measured liver fat and stiffness and serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. We assessed whether observed associations were mediated through fat mass at the time of outcome assessment. METHODS: Participants were from the Avon Longitudinal Study of Parents and Children. Trajectories of energy and macronutrient intake from ages 3-13 y were obtained with linear-spline multilevel models. Linear and logistic regression models examined whether energy intake and absolute and energy-adjusted macronutrient intake at ages 3, 7, and 13 y were associated with liver outcomes. RESULTS: Energy intake at all ages was positively associated with liver outcomes; for example, the odds of having a USS-measured liver fat per 100 kcal increase in energy intake at age 3 y were 1.79 (95% CI: 1.14, 2.79). Associations between absolute macronutrient intake and liver outcomes were inconsistent and attenuated to the null after adjustment for total energy intake. The majority of associations attenuated to the null after adjustment for fat mass at the time liver outcomes were assessed. CONCLUSION: Higher childhood and early adolescent energy intake is associated with greater NAFLD risk, and the macronutrients from which energy intake is derived are less important. These associations appear to be mediated, at least in part, by fat mass at the time of outcome assessment.


Subject(s)
Adolescent Development , Child Development , Child Nutritional Physiological Phenomena , Diet/adverse effects , Energy Intake , Hyperphagia/physiopathology , Non-alcoholic Fatty Liver Disease/etiology , Adolescent , Adolescent Nutritional Physiological Phenomena , Child , Child, Preschool , Cohort Studies , England/epidemiology , Female , Humans , Lipid Metabolism , Liver/diagnostic imaging , Liver/metabolism , Liver/physiopathology , Longitudinal Studies , Male , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/physiopathology , Prevalence , Prospective Studies , Risk Factors , Ultrasonography
14.
J Hypertens ; 33(3): 546-52; discussion 553, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25426570

ABSTRACT

OBJECTIVES: We aimed to determine the association of nonalcoholic fatty liver disease (NAFLD) with central and peripheral blood pressure (BP), in a general adolescent population and to examine whether associations are independent of adiposity. METHODS: Using cross-sectional data from a subsample (N = 1904) of a UK birth cohort, we assessed markers of NAFLD including ultrasound scan (USS) determined fatty liver, shear velocity (marker of liver fibrosis), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) at a mean age of 17.8 years. These were related to BP [central and peripheral SBP and DBP and mean arterial pressure (MAP)]. RESULTS: Fatty liver was positively associated with central and peripheral SBP, DBP and MAP in models adjusting for age, sex, social class, puberty and alcohol intake. These positive associations were attenuated to the null when fat mass was included. For example, in confounder-adjusted models, not including fat mass, mean central SBP was 3.74 mmHg [95% confidence interval (CI) 1.12 to 6.36] higher in adolescents with USS fatty liver than in those without; with additional adjustment for fat mass, the association attenuated to the null value (-0.37 mmHg; 95% CI -3.09 to 2.36). Similar patterns were found for associations of ALT and GGT with central and peripheral BP. There was no consistent evidence of associations of shear velocity or AST with BP measurements. Fatty liver was not consistently associated with central pulse pressure (PP), peripheral PP and Aix@75. CONCLUSION: NAFLD is not associated with higher central or peripheral BP in adolescents once confounding by adiposity is taken into account.


Subject(s)
Adiposity/physiology , Blood Pressure/physiology , Non-alcoholic Fatty Liver Disease/physiopathology , Obesity/physiopathology , Adolescent , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers , Cross-Sectional Studies , Female , Humans , Male , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Obesity/blood , Obesity/diagnostic imaging , Risk Factors , Ultrasonography , gamma-Glutamyltransferase/blood
15.
J Hepatol ; 61(3): 626-32, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24768828

ABSTRACT

BACKGROUND & AIMS: Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. METHODS: Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0-3 months, 3 months-1 y, 1-3 y, 3-7 y, and 7-10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. RESULTS: Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1-3 y, 3-7 y, and 7-10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. CONCLUSIONS: Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.


Subject(s)
Aging/physiology , Body Height/physiology , Body Weight/physiology , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/physiopathology , Patient Outcome Assessment , Adolescent , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Child , Child, Preschool , Cohort Studies , Elasticity/physiology , Female , Humans , Infant , Infant, Newborn , Linear Models , Liver/diagnostic imaging , Liver/enzymology , Liver/physiopathology , Logistic Models , Longitudinal Studies , Male , Prospective Studies , Risk Factors , Sex Factors , Ultrasonography , gamma-Glutamyltransferase/blood
16.
J Clin Endocrinol Metab ; 99(3): E410-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24471572

ABSTRACT

CONTEXT: The impact of adolescent nonalcoholic fatty liver disease (NAFLD) on health, independent of fat mass, is unclear. OBJECTIVE: The objective of the study was to determine the independent (of total body fat) association of ultrasound scan (USS)-determined NAFLD with liver fibrosis, insulin resistance, and dyslipidemia among healthy adolescents. DESIGN: This was a cross-sectional analysis in participants from a UK birth cohort. PARTICIPANTS: One thousand eight hundred seventy-four (1059 female) individuals of a mean age of 17.9 years participated in the study. MAIN OUTCOMES: USS assessed liver stiffness (shear velocity, an indicator of fibrosis) and volume, fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin. RESULTS: The prevalence of NAFLD was 2.5% [95% confidence interval (CI) 1.8-3.3] and was the same in females and males. Dual-energy X-ray absorptiometry determined total body fat mass was strongly associated with USS NAFLD: odds ratio 3.15 (95% CI 2.44-4.07) per 1 SD (∼10 kg) fat mass. Those with NAFLD had larger liver volumes and greater shear velocity. They also had higher fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin and lower high-density lipoprotein cholesterol. Most associations were independent of total body fat. For example, after adjustment for fat mass and other confounders, hepatic shear velocity [mean difference 22.8% (95% CI 15.6-30.5)], triglyceride levels [23.6% (95% CI 6.0-44.2)], and insulin [39.4% (95% CI 10.7-75.5)] were greater in those with NAFLD compared with those without NAFLD. CONCLUSION: In healthy European adolescents, 2.5% have USS-defined NAFLD. Even after accounting for total body fat, those with NAFLD have more adverse levels of liver fibrosis and cardiometabolic risk factors.


Subject(s)
Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Fatty Liver/epidemiology , Liver Cirrhosis/epidemiology , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Adolescent , Body Composition , Cross-Sectional Studies , Fatty Liver/diagnostic imaging , Female , Humans , Liver Cirrhosis/diagnostic imaging , Male , Non-alcoholic Fatty Liver Disease , Risk Factors , Ultrasonography , United Kingdom/epidemiology
17.
J Clin Endocrinol Metab ; 97(11): E2109-13, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22879632

ABSTRACT

CONTEXT: Pancreatic atrophy is common in longstanding type 1 diabetes, but there are limited data concerning pancreas size at diagnosis. OBJECTIVE: Our objective was to determine whether pancreatic size was reduced in patients with recently diagnosed type 1 diabetes and assess whether pancreatic volume was related to residual ß-cell function or islet autoantibodies. DESIGN AND SETTING: We conducted a controlled cohort study with strict inclusion criteria, recruiting from hospital diabetes clinics between 2007 and 2010. PATIENTS AND HEALTHY CONTROLS: Participants included 20 male adult patients (median age 27 yr) with recent-onset type 1 diabetes (median duration 3.8 months) and 24 male healthy controls (median age 27 yr). INTERVENTION: Interventions included noninvasive magnetic resonance imaging, collection of fasting blood samples, and glucagon stimulation testing in patients. MAIN OUTCOME MEASURES: We compared pancreatic volume estimates between patients with recent-onset type 1 diabetes and healthy controls as planned a priori. RESULTS: Scans were analyzed by an experienced radiologist blinded to diabetes status. Pancreatic volume correlated with body weight in patients and controls (P = 0.007). After adjustment for body weight, mean pancreatic volume index was 26% less in patients (1.19 ml/kg, se 0.07 ml/kg) than in controls (1.61 ml/kg, se 0.08 ml/kg) (P = 0.001). No correlation was seen between pancreatic volume index in patients and diabetes duration, glucose or C-peptide levels, glycated hemoglobin, and islet autoantibodies. CONCLUSIONS: Pancreatic volume is reduced by 26% in patients with type 1 diabetes within months of diagnosis, suggesting that atrophy begins years before the onset of clinical disease. Pancreatic atrophy within individuals is therefore a potential clinical marker of disease progression.


Subject(s)
Diabetes Mellitus, Type 1/pathology , Pancreas/pathology , Adolescent , Adult , Atrophy , Blood Glucose , C-Peptide/blood , Cohort Studies , Diabetes Mellitus, Type 1/blood , Disease Progression , Humans , Insulin/blood , Magnetic Resonance Imaging , Male , Organ Size
18.
HPB (Oxford) ; 12(3): 181-7, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20590885

ABSTRACT

BACKGROUND: Computed tomography (CT) is the most common staging investigation in colorectal cancer (CRC). Up to 25% of patients are found to have previously undetected hepatic lesions when intraoperative ultrasound (IOUS) of the liver is used during CRC resection. We aimed to assess the ability of IOUS to detect additional liver lesions/metastases at primary colorectal resection, and to evaluate whether contrast-enhanced IOUS (CE-IOUS) improves the detection and characterization of hepatic lesions. METHODS: We performed a single-centre, prospective pilot study. At CRC resection, patients underwent IOUS of the liver. Contrast-enhanced IOUS of the liver was undertaken using i.v. sulphur hexafluoride micro-bubbles (SonoVue, 4.8 ml). Findings of CT, non-enhanced IOUS and CE-IOUS were compared. Changes in staging or management were noted. Additional lesions were corroborated with iron oxide magnetic resonance imaging (MRI). RESULTS: Among 21 patients, IOUS demonstrated additional lesions in seven (33%). Contrast altered the diagnosis of non-enhanced IOUS in four (20%) and changed the management strategy in three (14%) patients. Thus, IOUS in combination with the contrast agent altered the intraoperative or postoperative management plan in four patients. CONCLUSIONS: In the first study of its kind, early results suggest that the ability of IOUS to detect additional metastases is improved by CE-IOUS, and that this may impact on surgical staging and management.


Subject(s)
Adenocarcinoma/surgery , Colonic Neoplasms/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Rectal Neoplasms/surgery , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adult , Aged, 80 and over , Colonic Neoplasms/pathology , Contrast Media , Female , Humans , Intraoperative Care , Male , Middle Aged , Pilot Projects , Prospective Studies , Rectal Neoplasms/pathology , Sulfur Hexafluoride , Ultrasonography
19.
J Radiol Case Rep ; 4(5): 27-31, 2010.
Article in English | MEDLINE | ID: mdl-22470731

ABSTRACT

Aneurysms and pseudoaneurysms of the portal venous system are rarely seen following abdominal trauma but clinicians need to be aware of them as possible vascular complications following blunt trauma. This case report of a 10 year old boy following a handlebar injury demonstrates a clear causal relationship between trauma and portal venous pseudoaneurysm. Portal venous aneurysms have a prevalence of less than 0.4% and most are found in patients with underlying hepatocellular disease. Many are asymptomatic in which case surveillance is an accepted management strategy, with Doppler ultrasound proving useful. Complications including thrombosis, distal embolism, compression of the biliary tree and haemorrhage are usually indications for surgical management. Portal venous pseudoaneurysms may be managed conservatively but transcatheter embolisation can be used if there are ongoing complications or haemorrhage.

20.
Clin Imaging ; 33(3): 209-12, 2009.
Article in English | MEDLINE | ID: mdl-19411027

ABSTRACT

AIMS: To compare the clinical utility of contrast enhanced magnetic resonance imaging (MRI) to ultrasound (USS) and computed tomography (CT) in focal hepatic lesions (FHLs) METHODS: This retrospective study analysed 125 consecutive iron oxide enhanced (SPIO) MRI. RESULTS: MRI made a difference in 74% of patients who had USS and in 42% of patients who had a CT scan. In suspected cancer, MRI changed diagnosis in 58% and 37% (13/35), respectively. CONCLUSIONS: MRI is superior to other noninvasive imaging modalities for lesion identification and characterisation.


Subject(s)
Ferric Compounds , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Ultrasonography/methods , Adolescent , Adult , Aged , Aged, 80 and over , Contrast Media , Female , Humans , Image Enhancement , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
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