The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant‐based, ...low‐animal‐protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double‐blind randomized controlled proof‐of‐principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8‐week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro‐inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.
What's known on the subject? and What does the study add?
Many patients are eligible for more than one treatment option for prostate cancer. In usual care, urologists have a large influence on the ...treatment choice. Decision aids, providing balanced information on the pros and cons of different treatment options, improve the match between patient preferences and treatment received.
In men eligible for both surgery and external beam radiotherapy, treatment choice differed by hospital. Across the participating hospitals, the decision aid consistently led to fewer patients remaining undecided on their treatment preference and more patients choosing brachytherapy.
Objectives
To examine the treatment choice for localized prostate cancer in selected men who were eligible for both prostatectomy and radiotherapy.
To examine whether increased patient participation, using a decision aid, affected the treatment choice.
Patients and Methods
From 2008 to 2011, 240 patients with localized prostate cancer were enrolled from three separate hospitals.
They were selected to be eligible for both prostatectomy and external beam radiotherapy. Brachytherapy was a third option for about half of the patients.
In this randomized controlled trial, patients were randomized to a group which only discussed their treatment with their specialist (usual care group) and a group which received additional information from a decision aid presented by a researcher (decision aid group). The decision aid was based on a literature review.
Predictors of treatment choice were examined.
Results
Treatment choice was affected by the decision aid (P = 0.03) and by the hospital of intake (P < 0.001).
The decision aid led to more patients choosing brachytherapy (P = 0.02) and fewer patients remaining undecided (P < 0.05).
Prostatectomy remained the most frequently preferred treatment.
Age, tumour characteristics or pretreatment urinary, bowel or erectile functioning did not affect the choice in this selected group.
Patients choosing brachytherapy assigned more weight to convenience of the procedure and to maintaining erectile function.
Conclusions
Traditionally, patient characteristics differ between surgery and radiotherapy groups, but not in this selected group of patients.
Men eligible for both prostatectomy and radiotherapy mostly preferred prostatectomy, and the treatment choice was influenced by the hospital they visited.
Giving patients evidence‐based information, by means of a decision aid, led to an increase in brachytherapy.
Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors ...exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.
Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (
= 12) or autologous (
= 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.
Consumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.
In this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.
Objective
To develop and validate new regret scales and examine whether a decision aid affects different aspects of regret in the treatment choice for prostate cancer.
Methods
This was a multicentre ...trial (three sites) with imbalanced randomization (1 : 2). From 2008 to 2011, patients with localized prostate cancer were randomized 1 : 2 to usual care (N = 77) or usual care plus a decision aid presenting risks and benefits of different treatments (N = 163). The treatments were surgery and (external or interstitial) radiotherapy. Regret was assessed before, and 6 and 12 months after treatment, using the Decisional regret scale by Brehaut et al. (Medical Decision Making, 23, 2003, 281), and three new scales focusing on process, option and outcome regret. The relation between decision aid and regret was analysed by anova.
Results
The concurrent validity of the new regret scales was confirmed by correlations between regret and anxiety, depression, decision evaluation scales and health‐related quality of life. With a decision aid, patient participation was increased (P = 0.002), but regret was not. If anything, in patients with serious morbidity the decision aid resulted in a trend to less option regret and less Brehaut regret (P = 0.075 and P = 0.061, with effect sizes of 0.35 and 0.38, respectively). Exploratory analyses suggest that high‐risk patients benefitted most from the decision aid.
Conclusion
The new regret scales may be of value in distinguishing separate aspects of regret. In general, regret was not affected by the decision aid. In patients with serious morbidity, a trend to lower option regret with a decision aid was observed.
Recent literature suggests that tri-exponential models may provide additional information and fit liver intravoxel incoherent motion (IVIM) data more accurately than conventional bi-exponential ...models. However, voxel-wise fitting of IVIM results in noisy and unreliable parameter maps. For bi-exponential IVIM, neural networks (NN) were able to produce superior parameter maps than conventional least-squares (LSQ) generated images. Hence, to improve parameter map quality of tri-exponential IVIM, we developed an unsupervised physics-informed deep neural network (IVIM
3
-NET). We assessed its performance in simulations and in patients with non-alcoholic fatty liver disease (NAFLD) and compared outcomes with bi-exponential LSQ and NN fits and tri-exponential LSQ fits. Scanning was performed using a 3.0T free-breathing multi-slice diffusion-weighted single-shot echo-planar imaging sequence with 18 b-values. Images were analysed for visual quality, comparing the bi- and tri-exponential IVIM models for LSQ fits and NN fits using parameter-map signal-to-noise ratios (SNR) and adjusted
R
2
. IVIM parameters were compared to histological fibrosis, disease activity and steatosis grades. Parameter map quality improved with bi- and tri-exponential NN approaches, with a significant increase in average parameter-map SNR from 3.38 to 5.59 and 2.45 to 4.01 for bi- and tri-exponential LSQ and NN models respectively. In 33 out of 36 patients, the tri-exponential model exhibited higher adjusted
R
2
values than the bi-exponential model. Correlating IVIM data to liver histology showed that the bi- and tri-exponential NN outperformed both LSQ models for the majority of IVIM parameters (10 out of 15 significant correlations). Overall, our results support the use of a tri-exponential IVIM model in NAFLD. We show that the IVIM
3
-NET can be used to improve image quality compared to a tri-exponential LSQ fit and provides promising correlations with histopathology similar to the bi-exponential neural network fit, while generating potentially complementary additional parameters.
Exotosin (EXT) proteins are involved in the chain elongation step of heparan sulfate (HS) biosynthesis, which is intricately involved in organ development. Loss of function mutations (LOF) in EXT1 ...and EXT2 result in hereditary exostoses (HME). Interestingly, HS plays a role in pancreas development and beta-cell function, and genetic variations in EXT2 are associated with an increased risk for type 2 diabetes mellitus. We hypothesized that loss of function of EXT1 or EXT2 in subjects with hereditary multiple exostoses (HME) affects pancreatic insulin secretion capacity and development. We performed an oral glucose tolerance test (OGTT) followed by hyperglycemic clamps to investigate first-phase glucose-stimulated insulin secretion (GSIS) in HME patients and age and gender matched non-affected relatives. Pancreas volume was assessed with magnetic resonance imaging (MRI). OGTT did not reveal significant differences in glucose disposal, but there was a markedly lower GSIS in HME subjects during hyperglycemic clamp (iAUC HME: 0.72 0.46-1.16 vs. controls 1.53 0.69-3.36 nmol·l-1·min-1, p<0.05). Maximal insulin response following arginine challenge was also significantly attenuated (iAUC HME: 7.14 4.22-10.5 vs. controls 10.2 7.91-12.70 nmol·l-1·min-1 p<0.05), indicative of an impaired beta-cell reserve. MRI revealed a significantly smaller pancreatic volume in HME subjects (HME: 72.0±15.8 vs. controls 96.5±26.0 cm3 p = 0.04). In conclusion, loss of function of EXT proteins may affect beta-cell mass and insulin secretion capacity in humans, and render subjects at a higher risk of developing type 2 diabetes when exposed to environmental risk factors.
Background
Noninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) ...is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD.
Purpose
To examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores.
Study Type
Prospective, cohort.
Population
Thirty‐seven patients with NAFLD.
Field Strength/Sequence
Multiparametric MRI at 3.0 T consisted of magnetic resonance (MR) spectroscopy (MRS) with multi‐echo stimulated‐echo acquisition mode, magnitude‐based and three‐point Dixon using a two‐dimensional multi‐echo gradient echo, MR elastography (MRE) using a generalized multishot gradient‐recalled echo sequence and intravoxel incoherent motion (IVIM) using a multislice diffusion weighted single‐shot echo‐planar sequence.
Assessment
Histological steatosis grades were compared to proton density fat fraction measured by MRS (PDFFMRS), magnitude‐based MRI (PDFFMRI‐M), and three‐point Dixon (PDFFDixon), as well as FibroScan® controlled attenuation parameter (CAP). Fibrosis and disease activity were compared to IVIM and MRE. FibroScan® liver stiffness measurements were compared to fibrosis levels. Diagnostic performance of all imaging parameters was determined for distinction between simple steatosis and nonalcoholic steatohepatitis (NASH).
Statistical Tests
Spearman's rank test, Kruskal–Wallis test, Dunn's post‐hoc test with Holm‐Bonferroni P‐value adjustment, receiver operating characteristic curve analysis. A P‐value <0.05 was considered statistically significant.
Results
Histological steatosis grade correlated significantly with PDFFMRS (rs = 0.66, P < 0.001), PDFFMRI‐M (rs = 0.68, P < 0.001), and PDFFDixon (rs = 0.67, P < 0.001), whereas no correlation was found with CAP. MRE and IVIM diffusion and perfusion significantly correlated with disease activity (rs = 0.55, P < 0.001, rs = −0.40, P = 0.016, rs = −0.37, P = 0.027, respectively) and fibrosis (rs = 0.55, P < 0.001, rs = −0.46, P = 0.0051; rs = −0.53, P < 0.001, respectively). MRE and IVIM diffusion had the highest area‐under‐the‐curve for distinction between simple steatosis and NASH (0.79 and 0.73, respectively).
Data Conclusion
Multiparametric MRI is a promising method for noninvasive, accurate, and sensitive distinction between simple hepatic steatosis and NASH, as well as for the assessment of steatosis and fibrosis severity.
Level of Evidence
2
Technical Efficacy
2
The contribution of intestinal bacterial strains (gut microbiota) in the development of cardiometabolic disease is increasingly recognized as potential diagnostic and pharmacological target. Changes ...in the intestinal bacterial composition and subsequent altered diversity has been associated with presence of chronic low-grade inflammation of mesenteric visceral adipose tissue, a known feature of malign obesity which can eventually lead to insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. In this regard, both fecal transplantation studies as well as multiethnic prospective cohorts can help to identify the causally involved driving intestinal bacterial strains in human cardiometabolism. Ultimately, it is expected that novel diagnostic markers as well as therapeutics (pharmabiotics and vaccine strategies) can be developed.
An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially ...initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.
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