Visceral fat mass dynamics in a 2-year randomized STrength versus ENdurance training trial in people with obesity.

AIM: To compare the effectiveness of strength versus endurance training on reducing visceral fat in individuals with obesity. MATERIALS AND METHODS: For the STrength versus ENdurance (STEN) 24-month randomized clinical trial, we assigned 239 participants with abdominal obesity to either strength or endurance training (two to three times a week, 60 min/training session) in addition to standard nutritional counselling to promote a healthy diet. Changes in abdominal visceral adipose tissue (VAT) area quantified by magnetic resonance imaging after 12 months were defined as a primary endpoint. RESULTS: Participants (aged 44 years, 74% women, body mass index: 37 kg/m2, mean VAT volume: 4050 cm3) had an approximately 50% retention rate and a 30% good training programme adherence at 12 months. There was no difference between strength and endurance training in VAT volume dynamics after 12 and 24 months (p = .13). Only in the good adherence group did we find a trend for reduced VAT volume in both training regimens. Independently of the exercise programme, there was a continuous trend for moderate loss of abdominal subcutaneous AT volume, body fat mass, body mass index and improved parameters of insulin sensitivity. Although parameters of physical fitness improved upon both exercise interventions, the dynamics of resting energy expenditure, glucose and lipid metabolism parameters were not different between the intervention groups and did not significantly improve during the 2-year trial (p > .05). CONCLUSIONS: Despite heterogeneous individual training responses, strength and endurance training neither affected VAT volume nor key secondary endpoints differently.

Hybrid Surgery for Severe Mitral Valve Calcification: Limitations and Caveats for an Open Transcatheter Approach.

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 ± 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 ± 31 min and cardiopulmonary bypass was 137 ± 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This "off label" implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

Endoscopic sleeve gastroplasty: suturing the gastric fundus does not confer benefit.

BACKGROUND : There is heterogeneity regarding the technical aspects of endoscopic sleeve gastroplasty (ESG), such as applying fundal sutures. Our aim was to determine whether ESG with fundal suturing (ESG-FS) affects weight loss and the serious adverse event (SAE) rate when compared with ESG with no fundal suturing (ESG-NFS). METHODS: We conducted a two-center retrospective analysis of 247 patients who underwent ESG with or without fundal suturing. The primary outcome was percentage excess weight loss (%EWL) at 3, 6, and 12 months post-ESG. The secondary outcomes included the SAE rate and procedure duration. RESULTS: At 3, 6, and 12-months, ESG-NFS had a significantly greater mean %EWL compared with ESG-FS (38.4 % [standard deviation (SD) 15.3 %] vs. 31.2 % [SD 13.9 %], P = 0.001; 54.7 % [SD 19.2 %] vs. 37.7 % [SD 17.3 %], P < 0.001; 65.3 % [SD 21.1 %] vs. 40.6 % [SD 23.5 %], P < 0.001, respectively). There was no statistically significant difference in the SAE rates for ESG-NFS (n = 2; 2.0 %) and ESG-FS (n = 4; 2.6 %; P > 0.99). The mean procedure time was significantly shorter in the ESG-NFS group at 59.1 minutes (SD 32.7) vs. 93.0 minutes (35.5; P < 0.001), and a lower mean number of sutures were used, with 5.7 (SD 1.1) vs. 8.4 (SD 1.6; P < 0.001). CONCLUSION : ESG-NFS demonstrated greater efficacy and shorter procedure duration. Therefore, fundal suturing should not be performed.

Transoral outlet reduction: could additional sutures cause more harm?

BACKGROUND: The double purse-string pattern (DPSP) of transoral outlet reduction (TORe) should conceivably result in a more robust scaffolding for the gastrojejunal anastomosis (GJA). However, there is a paucity of literature pertaining to post-TORe stenosis as an adverse event. Our aim was to determine the rate of stenosis, its potential predictors, and other complications of DPSP TORe. METHODS: We performed a retrospective analysis of a prospectively maintained database of 129 consecutive patients who underwent DPSP TORe between December 2015 and August 2019. RESULTS: The adverse event rate of TORe was 17.1 % (n = 22), with a 13.3 % (n = 17) rate of stenosis. Stenosis was not significantly associated with any baseline characteristics. GJA diameter pre- and post-TORe, the difference between these values, and procedure duration were not predictive of stenosis. Of patients who developed stenosis, 10 (58.8 %) responded to endoscopic balloon dilation and 7 (41.2 %) required stent placement. CONCLUSION: As the DPSP technique is a challenging procedure, with high complication rate and limited benefit, it should not be used for TORe.

Endobariatrics and Metabolic Endoscopy: Can We Solve the Obesity Epidemic with Our Scope?

PURPOSE OF REVIEW: Obesity is a chronic relapsing disease that results in cardiovascular disease, diabetes mellitus, and non-alcoholic fatty liver disease. Currently, surgery represents the most effective treatment. However, the advent of minimally invasive endoscopic bariatric therapy (EBT) has shifted the treatment paradigm to less invasive, cost-effective procedures with minimal complications and recovery time that are preferred by patients. In this review, we will describe current and future EBTs, focusing on outcomes and safety. RECENT FINDINGS: The endoscope has provided an incisionless portal into the gastrointestinal tract for placement of space-occupying devices and intraluminal procedures. EBTs are no longer solely manipulating anatomic alterations; instead, they aim to improve metabolic parameters such as glycated hemoglobin, low-density lipoprotein, cholesterol, and hepatic indices by targeting the mucosal layer of the gastrointestinal tract. The endoscope has succeeded in facilitating clinically meaningful weight loss and improvement of metabolic parameters. Future, solutions to the obesity epidemic will likely entail genetic testing, evaluation of the microbiome, and delivery of personalized therapy, utilizing combination endoscopic modalities that change the anatomy and physiology of individual patients, with new targets such as the abnormal metabolic signal.

Oral health-related quality of life of patients after heart transplantation and those with heart failure is associated with general health-related quality of life: a cross-sectional study.

PURPOSE: The aim of this cross-sectional study was to examine the oral health-related quality of life (OHRQoL) in patients after heart transplantation (HTx) and those with heart failure (HF). METHODS: In total, 186 participants (HTx: 104, HF: 82) were recruited from the University Department for Cardiac Surgery, Leipzig Heart Centre, Germany. OHRQoL was assessed with the German short form of the oral health impact profile (OHIP-G14). Health-related quality of life (HRQoL) was evaluated using the short form 36 survey (SF-36). Furthermore, the dental and periodontal treatment need was recorded. RESULTS: With an OHIP-G14 sum score of 6.58 ± 6.40 [5; 2.5-8] in the HTx group and 5.54 ± 5.47 [5; 2-7] in the HF group, no clinically relevant or statistically significant difference was apparent (p = 0.39). The SF-36 scales for physical functioning, role-physical, general health and vitality were significantly worse in the HF group compared with the HTx group (pi < 0.01). A worse SF-36 physical component summary was significantly associated with a higher OHIP-G14 sum score (HTx: p < 0.01, HF: p = 0.04). In the HTx group, a significant association was also observed for the mental component summary (p < 0.01). Multiple regression analysis revealed physical component summary (p = 0.04) and mental component summary (p < 0.01) in HTx, and physical component summary (p = 0.02), mental component summary (p = 0.02) and smoking (p < 0.01) as significant predictors for OHIP G14 in HF. CONCLUSION: The OHRQoL in HF and HTx patients appears to be mainly associated with general HRQoL. Therefore, multidisciplinary dental care concepts may be recommended to improve oral health conditions in these patients.

Real-World Safety and Efficacy of Fluid-Filled Dual Intragastric Balloon for Weight Loss.

BACKGROUND & AIMS: Reshape Duo is a saline-filled dual, integrated intragastric balloon (IGB) approved by the Food and Drug Administration for weight loss in patients with obesity. In a prospective, randomized trial, obese patients who received the balloon had significantly greater percent excess weight loss (%EWL) compared with patients treated with diet and exercise alone. However, there are limited data on the real-world efficacy of the Reshape balloon. METHODS: We performed a retrospective study of data collected from 2 academic centers and 5 private practices in which all patients paid for the IGB and follow-up visits out of pocket. The IGB was removed after 6 months. We collected data (demographic, medical, and laboratory) from 202 adults (mean age 47.8 ± 10.8 years; 83% female) with a baseline mean body mass index of 36.8 + 8.4 kg/m2 who had IGB insertion for weight loss therapy, along with counselling on lifestyle modifications focused on diet and exercise. Primary outcomes were percent total body weight loss (%TBWL) and %EWL at 1, 3, 6, 9, and 12 months after the procedure. RESULTS: Mean %TBWL at 1, 3, 6, 9 and 12 months was 4.8 ± 2.4%, 8.8 ± 4.3%, 11.4 ± 6.7%, 13.3 ± 7.8%, and 14.7 ± 11.8%, respectively. Data were available from 101 patients at 6 months and 12 patients at 12 months; 60.4% of patients achieved more than 10% TBWL and 55.4% had more than 25% EWL. Seventeen patients (8.4%) had esophageal tears during balloon insertion, with no intervention required. Thirteen patients (6.4%) had their IGB removed before the end of the 6-month treatment period. Nausea, vomiting, and abdominal pain were the most common adverse effects, occurring in 149 (73.8%), 99 (49%), and 51 (25.2%) patients. In one patient, the IGB migrated distally leading to small intestinal obstruction requiring surgical removal. CONCLUSION: In a retrospective analysis of real-world patients who received the Reshape Duo IGB, we found it to be a safe and efficacious endoscopic method for producing weight loss, with most patients achieving greater than 10% TBWL at 6 months.

Gastric mucosal devitalization reduces adiposity and improves lipid and glucose metabolism in obese rats.

BACKGROUND AND AIMS: The gastric mucosa is an endocrine organ that regulates satiation pathways by expression of orexigenic and anorexigenic hormones. Vertical sleeve gastrectomy (VSG) excludes gastric mucosa and reduces gastric volume. Our study aimed to investigate the independent effects of altering gastric mucosa on obesity and its related comorbidities. METHODS: Gastric mucosa devitalization (GMD) of 70% of the stomach was achieved by argon plasma coagulation in a high-fat diet rat model and was compared with VSG and sham surgery. In an 8-week follow-up study, we quantified body weight, visceral adiposity, insulin resistance index, cholesterol profiles, and free fatty acid profiles by enzyme-linked immunosorbent assay (ELISA). Following a 2-hour oral glucose tolerance test, the kinetics of ghrelin, glucagon-like peptide-1, peptide YY, and serum and liver bile acid levels were measured. Liver lipid content was quantified by ELISA. RESULTS: GMD resulted in significant reductions in body weight, visceral and subcutaneous adipose tissue, and hepatic steatosis as well as an improvement in lipid metabolism. GMD resulted in significant reductions in food intake and intestinal malabsorption of free fatty acids, both contributing to improved body composition and metabolic profile. Mechanistically, GMD resulted in a significant reduction in serum palmitate levels as well as an increase in serum and liver bile acid levels, known to alter glucose and lipid metabolism. Similar changes were noted when VSG rats were compared with sham surgery rats. CONCLUSIONS: Devitalization of gastric mucosa, independent of altering gastric volume, was able to reduce obesity-related comorbidities. The gastric mucosa may be a potential target for treating obesity and its associated comorbidities.

Gastric mucosal devitalization is safe and effective in reducing body weight and visceral adiposity in a porcine model.

BACKGROUND AND AIMS: The early improvement in metabolic profile after sleeve gastrectomy (SG) indicates that the significant benefits of metabolic surgery are gastric in origin. We have previously demonstrated that devitalization of the gastric mucosa (without a reduction in gastric volume) in metabolically disturbed obese rats results in an improvement of obesity and its associated comorbidities. The aims of this study were to assess the technical feasibility, efficacy, and safety of gastric mucosal devitalization (GMD) in a large animal (porcine) model. METHODS: A 3-arm (GMD versus SG versus sham [SH]) prospective randomized controlled trial with an 8-week follow-up period was performed. The primary endpoint was relative weight loss. Secondary endpoints were absolute body weight, abdominal visceral adiposity, abdominal subcutaneous adiposity, organ lipid content, and serum ghrelin level. RESULTS: GMD resulted in a significant relative weight loss of 36% over SH at 8 weeks (P < .05). There was no significant difference in relative weight loss between GMD and SG at 4 weeks; however, SG resulted in a 29% superior relative weight loss at 8 weeks (P < .05). With regard to visceral adiposity, there was a significant benefit of GMD over SH at 8 weeks. Despite differences in relative weight loss, there was no significant difference in visceral adiposity between SG and GMD at 8 weeks. Significant improvements in GMD over SH were noted with regard to skeletal and heart muscle lipid content. GMD pigs at 8 weeks demonstrated regeneration of the gastric mucosa without ulceration or significant scarring. Despite mucosal regeneration, the abundance of serum ghrelin was significantly lower in the GMD cohort compared with the SG and SH cohorts. CONCLUSIONS: GMD was technically feasible and resulted in relative weight loss and an improvement in visceral adiposity. The benefits noted were out of proportion to what would be expected with weight loss alone.

Metabolic in Vivo Labeling Highlights Differences of Metabolically Active Microbes from the Mucosal Gastrointestinal Microbiome between High-Fat and Normal Chow Diet.

The gastrointestinal microbiota in the gut interacts metabolically and immunologically with the host tissue in the contact zone of the mucus layer. For understanding the details of these interactions and especially their dynamics it is crucial to identify the metabolically active subset of the microbiome. This became possible by the development of stable isotope probing techniques, which have only sparsely been applied to microbiome research. We applied the in vivo stable isotope approach using 15N-labeled diet with subsequent identification of metabolically active bacterial species. Four-week old male Sprague-Dawley rats were randomly assigned to chow diet (CD, n =15) and high-fat diet (HFD, n =15). After 11 weeks, three animals from each group were sacrificed for baseline characterization of anthropometric and metabolic obesity. The remaining animals were exposed to either a 15N-labeled (n =9) or a 14N-unlabeled experimental diet (n =3). Three rats from each cohort (HFD and CD) were sacrificed at 12, 24, and 72 h. The remaining three animals from each cohort, which received the 14N-unlabeled diet, were sacrificed after 72 h. The colon was harvested and divided into three equal sections (proximal, medial, and distal), and the mucus layer of each specimen was sampled by scraping. We identified the active subset in an HFD model of obesity in comparison with lean controls rats using metaproteomics. In addition, all samples were investigated by 16S rRNA amplicon gene sequencing. The active microbiome of the HFD group showed an increase in bacterial taxa for Verrucomicrobia and Desulfovibrionaceae. In contrast with no significant changes in alpha diversity, time- and localization-dependent effects in beta-diversity were clearly observed. In terms of enzymatic functions the HFD group showed strong affected metabolic pathways such as energy production and carbohydrate metabolism. In vivo isotope labeling combined with metaproteomics provides a valuable method to distinguish the active from the non-active bacterial phylogenetic groups that are relevant for microbiota-host interaction. For morbid obesity such analysis may provide potentially new strategies for targeted pre- or probiotic treatments.

Primary endoscopic therapies for obesity and metabolic diseases.

PURPOSE OF REVIEW: Endoscopic approaches to obesity may help fulfill the unmet need of over half the US adult population who would benefit from therapy for obesity but are not receiving it. Endoluminal approaches have the potential to be more efficacious than antiobesity medications and have a lower risk-cost profile compared with bariatric surgery. This review outlines the current state of primary endoscopic weight loss and metabolic therapies and sheds light on the challenges faced toward making endoscopic bariatric therapies 'ready for prime time'. RECENT FINDINGS: Endoscopic approaches to obesity are being increasingly modeled on the proposed mechanisms contributing to the benefits of bariatric surgery.Therapies targeted at the stomach induce weight loss with only a proportional benefit to underlying metabolic disorders.Therapies targeting the proximal small bowel appear to modulate various neurohormonal pathways resulting in an improvement in metabolic profile in excess to that accounted for by weight loss itself. SUMMARY: Rigorous scientific assessment of endoscopic approaches to obesity is necessary to allow its integration into the treatment algorithm of obesity. The endoscopic armamentarium against obesity continues to evolve with the endoscopist poised to be a key player in the management of this disease. VIDEO ABSTRACT: http://links.lww.com/COG/A12.

Exercise training in patients with chronic heart failure promotes restoration of high-density lipoprotein functional properties.

RATIONALE: High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (NO) production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated. OBJECTIVE: This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF). METHODS AND RESULTS: HDL was isolated from 16 healthy controls (HDL(healthy)) and 16 patients with CHF-NYHA-III (HDL(NYHA-IIIb)) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDL(NYHA-II)). ECs were incubated with HDL, and phosphorylation of eNOS-Ser(1177), eNOS-Thr(495), PKC-ßII-Ser(660), and p70S6K-Ser(411) was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDL(NYHA-IIIb) triggered a lower stimulation of phosphorylation at eNOS-Ser(1177) and a higher phosphorylation at eNOS-Thr(495) when compared with HDL(healthy). This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-ßII by HDL(NYHA-IIIb), and a higher amount of malondialdehyde bound to HDL(NYHA-IIIb) compared with HDL(healthy) was measured. In healthy individuals, ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIb significantly improved HDL function. A correlation between changes in HDL-induced NO production and flow-mediated dilatation improvement by ET was evident. CONCLUSIONS: These results demonstrate that HDL function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF.

Establishing a reliable multiple reaction monitoring-based method for the quantification of obesity-associated comorbidities in serum and adipose tissue requires intensive clinical validation.

Multiple reaction monitoring (MRM)-based mass spectrometric quantification of peptides and their corresponding proteins has been successfully applied for biomarker validation in serum. The option of multiplexing offers the chance to analyze various proteins in parallel, which is especially important in obesity research. Here, biomarkers that reflect multiple comorbidities and allow monitoring of therapy outcomes are required. Besides the suitability of established MRM assays for serum protein quantification, it is also feasible for analysis of tissues secreting the markers of interest. Surprisingly, studies comparing MRM data sets with established methods are rare, and therefore the biological and clinical value of most analytes remains questionable. A MRM method using nano-UPLC-MS/MS for the quantification of obesity related surrogate markers for several comorbidities in serum, plasma, visceral and subcutaneous adipose tissue was established. Proteotypic peptides for complement C3, adiponectin, angiotensinogen, and plasma retinol binding protein (RBP4) were quantified using isotopic dilution analysis and compared to the standard ELISA method. MRM method variabilities were mainly below 10%. The comparison with other MS-based approaches showed a good correlation. However, large differences in absolute quantification for complement C3 and adiponectin were obtained compared to ELISA, while less marked differences were observed for angiotensinogen and RBP4. The verification of MRM in obesity was performed to discriminate first lean and obese phenotype and second to monitor excessive weight loss after gastric bypass surgery in a seven-month follow-up. The presented MRM assay was able to discriminate obese phenotype from lean and monitor weight loss related changes of surrogate markers. However, inclusion of additional biomarkers was necessary to interpret the MRM data on obesity phenotype properly. In summary, the development of disease-related MRMs should include a step of matching the MRM data with clinically approved standard methods and defining reference values in well-sized representative age, gender, and disease-matched cohorts.

Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure.

Recent research has disclosed a tight connection between obesity, metabolic gut microbial activities and host health. Obtaining a complete understanding of this relationship remains a major goal. Here, we conducted a comparative metagenomic and metaproteomic investigation of gut microbial communities in faecal samples taken from an obese and a lean adolescent. By analysing the diversity of 16S rDNA amplicons (10% operational phylogenetic units being common), 22 Mbp of consensus metagenome sequences (~70% common) and the expression profiles of 613 distinct proteins (82% common), we found that in the obese gut, the total microbiota was more abundant on the phylum Firmicutes (94.6%) as compared with Bacteroidetes (3.2%), although the metabolically active microbiota clearly behaves in a more homogeneous manner with both contributing equally. The lean gut showed a remarkable shift towards Bacteroidetes (18.9% total 16S rDNA), which become the most active fraction (81% proteins). Although the two gut communities maintained largely similar gene repertoires and functional profiles, improved pili- and flagella-mediated host colonization and improved capacity for both complementary aerobic and anaerobic de novo B(12) synthesis, 1,2-propanediol catabolism (most likely participating in de novo B(12) synthesis) and butyrate production were observed in the obese gut, whereas bacteria from lean gut seem to be more engaged in vitamin B(6) synthesis. Furthermore, this study provides functional evidence that variable combinations of species from different phyla could 'presumptively' fulfil overlapping and/or complementary functional roles required by the host, a scenario where minor bacterial taxa seem to be significant active contributors.

Four decades of experience of prosthetic valve endocarditis reflect a high variety of diverse pathogens.

Prosthetic valve endocarditis (PVE) remains a serious condition with a high mortality rate. Precise identification of the PVE-associated pathogen/s and their virulence is essential for successful therapy and patient survival. The commonly described PVE-associated pathogens are staphylococci, streptococci, and enterococci, with Staphylococcus aureus being the most frequently diagnosed species. Furthermore, multi-drug resistance pathogens are increasing in prevalence and continue to pose new challenges mandating a personalized approach. Blood cultures in combination with echocardiography are the most common methods to diagnose PVE, often being the only indication, it exists. In many cases, the diagnostic strategy recommended in the clinical guidelines does not identify the precise microbial agent, and frequently, false-negative blood cultures are reported. Despite the fact that blood culture findings are not always a good indicator of the actual PVE agent in the valve tissue, only a minority of re-operated prostheses are subjected to microbiological diagnostic evaluation. In this review, we focus on the diversity and the complete spectrum of PVE-associated bacterial, fungal, and viral pathogens in blood and prosthetic heart valve, their possible virulence potential, and their challenges in making a microbial diagnosis. We are curious to understand if the unacceptable high mortality of PVE is associated with the high number of negative microbial findings in connection with a possible PVE. Herein, we discuss the possibilities and limits of the diagnostic methods conventionally used and make recommendations for enhanced pathogen identification. We also show possible virulence factors of the most common PVE-associated pathogens and their clinical effects. Based on blood culture, molecular biological diagnostics, and specific valve examination, better derivations for the antibiotic therapy as well as possible preventive intervention can be established in the future.

Metaproteome analysis and molecular genetics of rat intestinal microbiota reveals section and localization resolved species distribution and enzymatic functionalities.

The digestion of food ingredients depends on the action of the gut microbiota and has a significant influence on the health, especially in the case of metabolic diseases, of the host organism. Despite the relevance of the structure and functionalities in the microbiota for the metabolism of the host, the spatial resolution of microbial consortia and the functionalities in the different gut sections of the rat are mostly unknown. Since there are suitable rat models for human metabolic diseases, the microbiota of the rat is of special interest. Samples along the intestinal tract of rats were investigated using metaproteomics and 16S rRNA gene pyrosequencing. The procedures for harvesting bacteria from the mucus and the content of the gut sections and feces were optimized leading to 2802 nonredundant bacterial protein groups in total that were assigned to spectra measured by liquid chromatography-tandem mass spectrometry. The majority of 16S rRNA genes and protein groups belonged to members of Firmicutes, Bacteroidetes and Proteobacteria. The functionalities in the enzyme repertoire were compared between the mucus and the content of the large intestine sections and the feces samples. This spatial resolution allowed pinpointing changes in the community to specific metabolic capacities like carbohydrate transport and energy conservation. The results showed that the mere analysis of feces samples reflects the functions of the gut microbiota only to a minor extent and sheds light on the metabolic interchange between the microbiota and the host organism.

Antioxidants prevent health-promoting effects of physical exercise in humans.

Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARgamma), and PPARgamma coactivators PGC1alpha and PGC1beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.

The role of pathogens in diabetes pathogenesis and the potential of immunoproteomics as a diagnostic and prognostic tool.

Diabetes mellitus (DM) is a group of metabolic diseases marked by hyperglycemia, which increases the risk of systemic infections. DM patients are at greater risk of hospitalization and mortality from bacterial, viral, and fungal infections. Poor glycemic control can result in skin, blood, bone, urinary, gastrointestinal, and respiratory tract infections and recurrent infections. Therefore, the evidence that infections play a critical role in DM progression and the hazard ratio for a person with DM dying from any infection is higher. Early diagnosis and better glycemic control can help prevent infections and improve treatment outcomes. Perhaps, half (49.7%) of the people living with DM are undiagnosed, resulting in a higher frequency of infections induced by the hyperglycemic milieu that favors immune dysfunction. Novel diagnostic and therapeutic markers for glycemic control and infection prevention are desirable. High-throughput blood-based immunoassays that screen infections and hyperglycemia are required to guide timely interventions and efficiently monitor treatment responses. The present review aims to collect information on the most common infections associated with DM, their origin, pathogenesis, and the potential of immunoproteomics assays in the early diagnosis of the infections. While infections are common in DM, their role in glycemic control and disease pathogenesis is poorly described. Nevertheless, more research is required to identify novel diagnostic and prognostic markers to understand DM pathogenesis and management of infections. Precise monitoring of diabetic infections by immunoproteomics may provide novel insights into disease pathogenesis and healthy prognosis.

Surgery for Aortic Prosthetic Valve Endocarditis in the Transcatheter Era.

Objectives: As surgical experience with infective endocarditis following transcatheter aortic valve replacement is scarce, this study compared the perioperative and short-term outcomes of patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement. Methods: Between January 2013 and December 2020, 468 consecutive patients were admitted to our center for surgery for IE. Among them, 98 were operated on for endocarditis following surgical aortic valve replacement and 22 for endocarditis following transcatheter aortic valve replacement. Results: The median EuroSCORE II (52.1 (40.6-62.0) v/s 45.4 (32.6-58.1), p = 0.207) and STS-PROM (1.8 (1.6-2.1) v/s 1.9 (1.4-2.2), p = 0.622) were comparable. Endocarditis following transcatheter aortic valve replacement accounted for 13.7% of the aortic prosthetic valve endocarditis between 2013 and 2015; this increased to 26.9% in the years 2019 and 2020.Concomitant procedures were performed in 35 patients (29.2%). The operative mortality was 26.5% in the endocarditis following surgical aortic valve replacement group and 9.1% in the endocarditis following transcatheter aortic valve replacement group (p = 0.098). Upon follow-up, survival at 6 months was found to be 98% in the group with endocarditis following surgical aortic valve replacement and 89% in the group with endocarditis following transcatheter aortic valve replacement (p = 0.081). Conclusions: Patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement present with comparable risk profiles and can be surgically treated with comparable results. Surgery as a curative option should not be rejected even in this intermediate-risk cohort.

Gastric Mucosal Devitalization (GMD): Using the Porcine Model to Develop a Novel Endoscopic Bariatric Approach.

BACKGROUND AND AIMS: As the pig model has similar gastrointestinal anatomy and physiology to humans, we used pigs to create a gastric mucosal devitalization (GMD) model in preparation for clinical translation of this technique as an endoscopic bariatric therapy (EBT). The aims of this study were to determine the ablation parameters and technique for a successful, safe, and feasible large surface area GMD that produces weight loss. METHODS: We performed GMD using argon plasma coagulation (APC) in 3 phases. Phase 1 assessed the ablation energy required to accomplish selective mucosal ablation using ex vivo pig stomachs (n = 2). Phase 2 assessed the optimal percentage of mucosal surface area to be treated and was performed on 10 pigs. Phase 3 assessed feasibility, efficacy, and safety with 8 pigs randomized into GMD (n = 4) or sham (SH, n = 4) and survived for 1 month. Body weights (GMD, n = 4, SH, n = 4) were measured daily in phase 3 for 1 month, and relative body weights were calculated and analyzed using one-tailed Student's t-test. Percent body fat was compared between GMD and SH at baseline and 1 month post-GMD. RESULTS: Phase 1 identified the optimal ablation parameters (120 W) that were then used in phase 2. Phase 2 revealed a trend that was suggestive that the optimal percent surface area to ablate was similar to that which is removed at laparoscopic sleeve gastrectomy. In phase 3, GMD was performed over 70% surface area of the greater curvature of the stomach in four pigs. GMD pigs had significantly lower relative body weight increase compared to SH at 1 month (1.375 ± 0.085 vs 1.575 ± 0.047, p = 0.0435). MRI showed a significantly lower body fat mass at 1 month in GMD pigs (5.9 ± 0.4% vs 12.7 ± 2.3%, p = 0.026) compared to SH. CONCLUSIONS: GMD resulted in decreased weight gain in the GMD group as evidenced by a lower relative body weight at 1 month. GMD in an animal model appears to show promise as a potential weight loss therapy.