Background Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30–35 kg/m2). Methods DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass—RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. Results Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. Conclusions This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. Trial registration: ISRCTN53984585

Background This study aimed to evaluate atrium extracellular matrix remodeling in atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets. Methods A posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to aortic valve replacement surgery in a tertiary hospital were selected. Results Fibrosis was significantly increased in the AF group when compared to sinus rhythm (SR) patients (p = 0.024). Moreover, cardiomyocyte area was significantly higher in AF patients versus SR patients (p = 0.008). Conversely, collagen III gene expression was increased in AF patients (p = 0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/TIMP4 ratio was significantly decreased in AF patients (p = 0.006). TIMP1 (p = 0.004) and TIMP2 (p = 0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p = 0.0159) and mean (p = 0.031) gradients demonstrated a negative association with serum TIMP1. Conclusions Atrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.

Aims Risk stratification in acute heart failure (HF) patients can help to decide therapies and time for discharge. The potential of growth differentiation factor 15 (GDF-15) in HF has been previously shown. We aimed to study the importance of GDF-15level variations in acute HF patients. Methods and resultsWe retrospectively evaluated a cohort of patients hospitalized due to acute HF. GDF-15 was measured both at admission and on the discharge day. Patients were followed-up during a 3 year period. The endpoint under analysis was all-cause mortality. GDF-15 variation is equal to [(admission GDF-15 À discharge GDF-15)∕admission GDF-15] × 100. Variation was categorized in levels of increase or decrease of GDF-15. Patients were cross-classified according to admission and discharge GDF-15 cut-off points. A Cox regression analysis was used to assess the prognostic impact of GDF-15 variation and the impact of both admission and discharge GDF-15 according to the cross-classification. We studied a group of 249 patients with high co-morbidity burden. Eighty-one patients died at 1 year and 147 within 3 years. There was a modest decrease in GDF-15 during hospitalization from a median value of 4087 to 3671 ng/mL (P = 0.02). No association existed between GDF-15 variation and mortality. In multivariate analysis, patients with admission GDF-15 ≥ 3500 ng/mL and discharge GDF-15 ≥ 3000 ng/mL had a significantly higher 1 year death risk when compared with the remaining-hazard ratio = 2.59 (95% confidence interval: 1.41-4.76)-and a 3 year 1.76 (95% confidence interval: 1.08-2.87) higher death risk compared with those with both values below the cut-off. Conclusions Growth differentiation factor 15 decreased during an acute HF hospitalization, but its variation had no prognostic implications. The knowledge of both admission and discharge GDF-15 added meaningful information to patients' risk stratification.