External validation of the fatty liver index and lipid accumulation product indices, using H-1-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals

Background and Aims. Simple clinical algorithms including the Fatty Liver Index (FLI) and Lipid Accumulation Product (LAP) have been developed as a surrogate marker for Non-Alcoholic Fatty Liver Disease (NAFLD). These algorithms have been constructed using ultrasonography, a semi-quantitative method. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as measured quantitatively by proton magnetic resonance spectroscopy (1H-MRS). Methods. Data were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment in the course of research studies. Values of FLI and LAP were determined, and assessed both as predictors of the presence of hepatic steatosis (liver fat >5.5 %) and of actual liver fat content, as measured by 1H MRS. The discriminative ability of FLI and LAP was estimated using the area under the Receiver Operator Characteristic curve (AUROC). Since FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Results. FLI and LAP discriminated between patients with and without hepatic steatosis with an AUROC of 0.79 (IQR= 0.74, 0.84) and 0.78 (IQR= 0.72, 0.83), although quantitative prediction of liver fat content was unsuccessful. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort. Conclusions. FLI and LAP may be used clinically, and for metabolic and epidemiological research, to identify patients with hepatic steatosis, but not as surrogates for liver fat content

Circulating pancreatic polypeptide concentrations predict visceral and liver fat content

CONTEXT AND OBJECTIVE: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat. PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy. RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01). CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition

Insulin Detemir Reduces Weight Gain as a Result of Reduced Food Intake in Patients With Type 1 Diabetes

Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure

Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in non-alcoholic fatty liver disease (NAFLD).

AIMS: Supervised exercise reduces liver fat and improves endothelial function, a surrogate of cardiovascular disease risk, in non-alcoholic fatty liver disease (NAFLD). We hypothesised that after a 16-week supervised exercise program, patients would maintain longer-term improvements in cardiorespiratory fitness, liver fat and endothelial function. MATHERIALS AND METHODS: Ten NAFLD patients [5/5 males/females, age 51±13years, BMI 31±3 kg.m(2) (mean±s.d.)] underwent a 16-week supervised moderate-intensity exercise intervention. Biochemical markers, cardiorespiratory fitness (VO2peak), subcutaneous, visceral and liver fat (measured by magnetic resonance imaging and spectroscopy respectively) and brachial artery flow-mediated dilation (FMD) were assessed at baseline, after 16 weeks supervised training and 12-months after ending supervision. RESULTS: Despite no significant change in body weight, there were significant improvements in VO2peak [6.5 ml.kg(-1).min(-1) (95% CI 2.8, 10.1); P=0.003], FMD [2.9% (1.5, 4.2); P=0.001], liver transaminases (P0.05) and liver fat [1.4% (-13.0, 15.9); P=0.83] were not significantly different from baseline. CONCLUSIONS: Twelve months following cessation of supervision, exercise-mediated improvements in liver fat and other cardiometabolic variables had reversed with cardiorespiratory fitness at baseline levels. Maintenance of high cardiorespiratory fitness and stability of body weight are critical public health considerations for the treatment of NAFLD.International Journal of Obesity accepted article preview online, 21 July 2016. doi:10.1038/ijo.2016.123

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The 'subscription-type' model was viewed favourably by infection consultants in England

Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients

Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical examination. Samples were analysed for sMMP-9 concentration (enzyme-linked immuno-sorbant assay) and compared to final diagnoses. Logistic regression modelling determined independent factors associated with neoplasia. A total of 365 patients were recruited of whom 300 were analysed, including 46 normal controls. A total of 27 significant adenomas and 63 malignancies were identified. The median sMMP-9 concentration was 443ng ml−1 (IQR: 219–782; mean: 546). Patients with neoplasia had significantly elevated sMMP-9 levels (P<0.001). Logistic regression modelling identified elevated log(sMMP-9) as the most significant predictor of neoplasia (χ2=38.33, P<0.001). Other significant factors were age, sex, smoking history, abdominal pain and weight loss. The model accurately predicted neoplasia in 77.3% of cases. Sensitivity and specificity were 77.9 and 77.1%. sMMP-9 estimation can accurately stratify patient to low- or high-risk cohorts. Serum sampling is a potential means of avoiding unnecessary colonoscopy and reducing patient anxiety, iatrogenic morbidity and mortality, and cost

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel ‘subscription-type’ funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting). Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both ‘subscription-type’ model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The ‘subscription-type’ model was viewed favourably by infection consultants in England

Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden

<p/> <p>Background</p> <p>Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts.</p> <p>Findings</p> <p>SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months.</p> <p>Conclusion</p> <p>Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.</p