Ythdf2 regulates cardiac remodeling through its mRNA target transcripts.

m6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytes in vivo leads to mild cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. Similarly, in vitro the knockdown of Ythdf2 results in cardiomyocyte growth and remodeling. Mechanistically, we identified the eucaryotic elongation factor 2 as post-transcriptionally regulated by Ythdf2 using cell type specific Ribo-seq data. Our study expands our understanding on the regulatory functions of m6A methylation in cardiomyocytes and how cardiac function is controlled by the m6A reader protein Ythdf2.

One-stage versus two-stage Roux-Y gastric bypass as redo surgery of failed adjustable gastric banding.

INTRODUCTION: The study focussed on whether a one-stage Roux-Y gastric bypass (OS-RYGB) or a two-stage RYGB (TS-RYGB) has a significant advantage in terms of perioperative risk in patients after failed adjustable gastric banding (AGB). METHODS: Data collection included patients who underwent OS-RYGB or TS-RYGB after AGB between 2005 and 2019 and whose outcomes were compared with those after primary RYGB (P-RYGB). Outcome criteria were perioperative complications, comorbidities, 30-day mortality and operating time. RESULTS: The study analysed data from patients who underwent OS-RYGB (N = 525), TS-RYGB (N = 382) and P-RYGB (N = 26,445). Intraoperative and postoperative complication rates were significantly lower for P-RYGB (p < 0.001). Total intraoperative and specific postoperative complication rates were significantly lower in TS-RYGB than in OS-RYGB (p = 0.048 and p < 0.001, respectively). In contrast, the total general postoperative complication rate was lower in OS-RYGB than in TS-RYGB (p < 0.001). The mean operating time differed significantly among the three groups (P-RYGB 96.5min, OS-RYGB 141.2min and TS-RYGB 190.9min; p < 0.001). The mortality rate was not significantly different between the three groups. CONCLUSIONS: Based on the significant difference between the two groups in revision surgery and the slight difference with the results of primary RYGB, this study concludes that removal of a failed AGB is safe and feasible with either the OS- or TS-RYGB procedure. However, we cannot directly recommend either procedure in our study. Proper patient selection and surgeon experience are critical to avoid potential adverse effects.

Perceived Barriers in the Decision for Bariatric and Metabolic Surgery: Results from a Representative Study in Germany.

BACKGROUND: Attitudes of the general public may be an influencing factor for low surgery rates: When skepticism is high, support for individuals wanting or needing to undergo surgery may diminish. This study assesses the relevance of barriers to metabolic surgery. METHODS: The study was conducted using a representative sample of the German population (n = 1007). Participants were asked to imagine that they would have to decide for or against metabolic surgery and rate how this decision would be influenced by a number of reasons given to them (Likert scale). Results are presented by weight status. RESULTS: The barrier found most irrelevant is that surgery could be considered cheating across all weight groups. About a fourth of the sample state that not knowing enough about surgery (28.5%), being afraid of surgery (28.3%), and potential negative consequences after surgery (24.5%) are reasons against metabolic surgery that were rated extremely relevant. Having obesity was a significant predictor of endorsement in two variables: feeling like cheating (lower probability for relevance, OR = 0.58, p = 0.025) and a lack of knowledge (lower probability for relevance, OR = 0.59, p = 0.031). CONCLUSIONS: In summary, the public's view of weight loss surgery lacks information about post-surgical consequences. It is important to address these points in the public and in social networks of patients as they may be pre- or antecedent of surgery stigma.

[Referral behavior of general physicians for patients with obesity]. / Zuweisungsverhalten der Hausärzte bei Patienten mit Adipositas.

The prevalence of obesity and overweight is constantly rising. Thus, obesity is increasingly considered as one of the most important healthcare problems in Germany. Surgical interventions have been proven to be the only treatment option to achieve sustained weight loss along with a reduction of obesity-related comorbidities in the vast majority of morbidly obese patients. With respect to the small numbers of weight loss surgeries conducted in Germany, several reasons are currently discussed. General practitioners play a very important role in gatekeeping when it comes to decisions about treatment. Research has shown that knowledge and stigma play a role when treatment pathways for patients with obesity are defined. Interventions are required to make treatment decisions by physicians or patients independent of social pressure due to stigma or gaps in expertise.

Changes in Attitudes Towards Bariatric Surgery After 5 Years in the German General Public.

PURPOSE: The aim of this study was to investigate changes in attitudes of the general public towards bariatric surgery and other interventions that can be part of obesity management, during the last 5 years. METHOD: 1007 participants were randomly selected and interviewed. Apart from socio-demographic data, interviews also included causal reasons for obesity as well as questions regarding treatment methods and their believed effectiveness. Results were compared with data published 5 years ago. RESULTS: Surgery is seen as a rather ineffective method to reduce weight in obesity and is recommended less often by the general public compared to the assessment 5 years ago. CONCLUSIONS: Public health-implications should inform about obesity and benefits of surgery as an intervention to improve individual health conditions.

Closed-loop gastric electrical stimulation versus laparoscopic adjustable gastric band for the treatment of obesity: a randomized 12-month multicenter study.

OBJECTIVE: To compare the weight loss, change in quality of life (QOL) and safety of closed-loop gastric electrical stimulation (CLGES) versus adjustable gastric band (LAGB) in the treatment of obesity. METHODS: This multicenter, randomized, non-inferiority trial randomly assigned the patients in a 2:1 ratio to laparoscopic CLGES versus LAGB and followed them for 1 year. We enrolled 210 patients, of whom 50 were withdrawn preoperatively. Among 160 remaining patients (mean age=39±11 years; 75% women; mean body mass index=43±6 kg m-2) 106 received CLGES and 54 received LAGB. The first primary end point was non-inferiority of CLGES versus LAGB, ascertained by the proportion of patients who, at 1 year, fulfilled: (a) a ⩾20% excess weight loss (EWL); (b) no major device- or procedure-related adverse event (AE); and (c) no major, adverse change in QOL. Furthermore, ⩾50% of patients had to reach ⩾25% EWL. The incidence and seriousness of all AE were analyzed and compared using Mann-Whitney's U-test. RESULTS: At 1 year, the proportions of patients who reached all components of the primary study end point were 66.7 and 73.0% for the LAGB and CLGES group, respectively, with a difference of -6.3% and an upper 95% CI of 7.2%, less than the predetermined 10% margin for confirming the non-inferiority of CLGES. The second primary end point was also met, as 61.3% of patients in the CLGES group reached ⩾25% EWL (lower 95% CI=52.0%; P<0.01). QOL improved significantly and similarly in both groups. AE were significantly fewer and less severe in the CLGES than in the LAGB group (P<0.001). CONCLUSIONS AND RELEVANCE: This randomized study confirmed the non-inferiority of CLGES compared with LAGB based on the predetermined composite end point. CLGES was associated with significantly fewer major AE.

[Nutritional deficiencies and supplementation after metabolic surgery]. / Nutritive Defizite und Supplementation nach metabolischer Chirurgie.

Increasing prevalence of morbid obesity in Germany is associated with an increasing number of bariatric surgical interventions.Based on the effectiveness of bariatric surgery with regard to a significant reduction of body weight and comorbidity as well as improvement of the quality of life compared with conservative measures, its value and impact has been substantially increased. Long-term metabolic deficits such as nutrient deficiencies can be considered the main risks of various restrictive, combined and malabsorptive procedures of bariatric surgery.The aim of this overview is to characterize metabolic complications after bariatric surgery and their prophylaxis, which require a temporary or permanent surveillance and, if necessary, effective supplementation.Bariatric surgical interventions such as gastric banding (GB) and sleeve gastrectomy (SG) can be subsequently associated with deficiencies related to B­vitamins whereas iron, folate, and vitamins B1, B12 and D deficiencies might be consequences of malabsorptive procedures such as biliopancreatic diversion, duodenal switch and Roux-en-Y gastric bypass.Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long follow-up investigations. The currently available guidelines of the American Association of Bariatric and Metabolic Surgery are the basis for the latest recommendations on supplementation and treatment in bariatric surgery.

Risk of thrombosis and thromboembolic prophylaxis in obesity surgery: data analysis from the German Bariatric Surgery Registry.

BACKGROUND: Evidence-based data on optimal approach for prophylaxis of deep venous thrombosis (VTE) and pulmonary embolism (PE) in bariatric operations is discussed. Using antithrombotic prophylaxis, weight adjusted the risk of VTE and its complications have to be balanced with the increased bleeding risk. METHODS: Since 2005, the current situation for bariatric surgery has been examined by quality assurance study in Germany. As a prospective multicenter observational study, data on the type, regimen, and time course of VTE prophylaxis were documented. The incidences of clinically diagnosed VTE or PE were derived during the in-hospital course and follow up. RESULTS: Overall, 31,668 primary bariatric procedures were performed between January 2005 and December 2013. Most performed operations were 3999 gastric banding (GB); 13,722 Roux-en-Y-gastric bypass (RYGBP); and 11,840 sleeve gastrectomies (SG). Gender (p = 0.945), surgical procedure (p = 0.666), or administration of thromboembolic prophylaxis (p = 0.272) had no statistical impact on the DVT incidence. By contrast, BMI (p = 0.116) and the duration of thromboembolic prophylaxis (p = 0.127) did impact the frequency of onset of DVT. CONCLUSION: Age, BMI, male gender, and a previous history of VTE are the most important risk factors. The drug of choice for VTE is heparin. LMWH should be given preference over unfractionated heparins due to their improved pharmacological properties, i.e., better bioavailability and longer half-life as well as ease of use. Despite the low incidence of VTE and PE, there is a lack of evidence. Therefore, prospective randomized studies are necessary to determine the optimal VTE prophylaxis for bariatric surgical patients.

[Current Situation of Antibiotic Prophylaxis in Obesity and Metabolic Surgery - Data Analysis from the Study for Quality Assurance in Operative Treatment of Obesity in Germany]. / Aktueller Stand der Antibiotikaprophylaxe in der Adipositas- und metabolischen Chirurgie - Datenanalyse aus der Studie zur Qualitätskontrolle der operativen Therapie der Adipositas in Deutschland.

BACKGROUND: Since January 2005, the situation of metabolic and obesity surgery in Germany has been constantly evaluated by the German Bariatric Surgery Registry (GBSR). Data registration is performed using an internet online database with prospective data collection. All registered data were analysed in cooperation with the Institute of Quality Assurance at the Otto-von-Guericke University Magdeburg. METHODS: Data collection includes primary and revision/redo-procedures. A main focus of the current study is the analysis of data regarding the perioperative management, in particular, administration of antibiotics. RESULTS: Since 2005 a significant increase of primary bariatric procedures has been reported. For evaluation of the antibiotic regimen 12 296 primary operations including 684 balloons (BIB), 2950 gastric bandings (GB), 5115 Roux-en-Y-gastric bypasses (RYGBP), 120 Scopinaro's biliopancreatic diversions (BPD), 164 duodenal switches (DS), 3125 sleeve gastrectomies (SG) and 138 other procedures were analysed. In total 77.3 % of the patients with primary procedures received perioperative antibiotics. Patients without concomitant comorbidities received antibiotics significantly less often compared to those with comorbidities. Wound infection rates were comparable for patients who underwent either gastric banding or sleeve gastrectomy. CONCLUSION: Surgery has been accepted step by step as a treatment for morbid obesity and its comorbidities in Germany during the last few years. There is only little experience in the literature regarding antibiotic therapy as well as prophylaxis in bariatric surgery. Based on the results of the current study we recommend rather the selective than the routine use of antibiotics depending on different parameters, e.g., operative time, preoperative BMI and concomitant comorbidities.

[Comment on Gender-Specific Aspects in Obesity and Metabolic Surgery--Analysis of Data from the German Bariatric Surgery Registry]. / Kommentar zu genderspezifischen Aspekten in der Adipositas- und metabolischen Chirurgie--Daten der Qualitätssicherungsstudie für operative Therapie der Adipositas.

BACKGROUND: The current situation in obesity and metabolic surgery since January 2005 has been investigated with the help of the quality assurance study on surgical therapy for obesity = German Bariatric Surgery Registry (GBSR). The data were acquired and analysed in cooperation with the Institute for Quality Assurance in Surgical Medicine at the Otto-von-Guericke University. METHODS: Data acquisition was done with the help of an online database. On a voluntary basis, all obesity and metabolic surgical interventions since 2005 have been recorded. In addition to the surgical data, the findings of the yearly follow-up investigations were recorded. RESULTS: Since 2005 there have been 1,263 gastric balloon procedures, 11,840 sleeve gastrectomies, 13,722 Roux-en-Y gastric bypasses and 3999 gastric banding operations. The average age of the male patients in all interventions was significantly higher. The average BMI of female patients who received a gastric banding or a gastric balloon procedure was significantly lower than that of the male patients. Men exhibited a higher incidence of comorbidities than women. CONCLUSION: The number of obesity and metabolic surgical interventions in Germany is continuously increasing. The results of the study on surgical therapy for obesity (GBSR) reveal significant differences in the gender-specific incidence of preoperative comorbidities. postoperative complications and mortality. Further studies on gender-specific aspects are necessary in order to optimise patient selection and reduce the incidence of postoperative complications.

[Management of complications in bariatric surgery]. / Management von Frühkomplikationen in der Adipositaschirurgie.

Bariatric surgery is known to be the most effective and long-lasting treatment for morbid obesity and associated comorbidities. These comorbidities together with cardiopulmonary decompensation make morbidly obese patients a high risk group for operative interventions. Early detection of postoperative complications is a challenging task in these patients and requires accurate and timely interpretation of any alarm signals. Symptoms, such as tachycardia and abdominal pain are highly suspicious. The same applies to elevated inflammatory parameters and fever. Early diagnostic laparoscopy is mandatory once cardiopulmonary complications have been excluded. Moreover, it has a higher sensitivity and specificity than other radiological modalities and is a minimally invasive procedure with a highly satisfactory outcome.

[Revisional surgery and reoperations in obesity and metabolic surgery : Data analysis of the German bariatric surgery registry 2005-2012]. / Revisions- und "Redo"-Eingriffe in der Adipositas- und metabolischen Chirurgie : Datenanalyse des German Bariatric Surgery Registry 2005-2012.

BACKGROUND: Increasing numbers of interventions for obesity and metabolic surgery have led to an increase of primary bariatric operations as well as redo operations and revisional surgery after various primary bariatric procedures. Evidence-based guidelines for indications and choice of procedure for revisional surgery do not currently exist. AIM: The spectrum of various revisional and redo operations following standard operative procedures for obesity and metabolic surgery is presented based on current data from the German bariatric surgery registry (GBSR, German nationwide survey on quality assurance in bariatric surgery) and a literature search. MATERIAL AND METHODS: Since 1 January 2005, the current situation of bariatric surgery has been examined using the GBSR. All data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University Magdeburg. Since 2005 a total of 24,070 primary bariatric procedures, 2070 revisional procedures and 1124 redo operations were analyzed. The study evaluated 1021 revisional and 491 redo operations after gastric banding (GB), 443 redo operations after sleeve gastrectomy (SG) and 306 revisional procedures and 10 redo operations after a Roux-en-Y gastric bypass (RYGBP). RESULTS: Reoperations of GB to SG were performed in 240 cases. The complication rate for GB removal and SG showed a significantly higher leakage rate for one step operations than for two step procedures of 3.3% vs. 0.0%. Conversion of GB to RYGBP was performed in 402 operations without any significant differences between one and two step approaches (1.9% vs. 2.2%). The specific complication rate in the 443 interventions in patients for conversion from SG to RYGBP was 10.8% which is higher than for primary SG (4.9%) and RYGBP (5.3%). CONCLUSION: Compared with the primary surgical procedures redo operations and revisional procedures have significantly higher complication rates. The data evaluated show that strong and differentiated indications are necessary for revisional and redo operations particularly in cases of therapy or metabolic failure.

[Nutrient Deficiencies after Bariatric Surgery - Systematic Literature Review and Suggestions for Diagnostics and Treatment]. / Nutritive Defizite nach bariatrischer Chirurgie - systematische Literaturanalyse und Empfehlungen für Diagnostik und Substitution.

The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered the main risks of metabolic surgery and its restrictive and malabsorbant surgical procedures. The aim of this compact short overview based on a selective literature search and our own clinical experience is to characterise the long-term metabolic complications, which are specific for the various bariatric procedures, and to refine the published guidelines for supplementation. Restrictive bariatric procedures can be associated with well-known surgical problems such as pouch dilatation or band migration, e.g., after gastric banding. After sleeve gastrectomy, emerging reflux disease can become a substantial problem. The most frequent deficiencies after restrictive procedures are related to B-vitamins whereas iron, folate, vitamin B1 and B12 and vitamin D deficiencies are associated with the malabsorptive procedure such as biliopancreatic diversion, duodenal switch and Roux-en-Y gastric bypass. Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical follow-up investigations. The currently available guidelines of German Society of Treatment of Obesity (CAADIP) of DGAV for supplementation should be known and followed, in particular, by the physicians who i) are exceptionally involved in medical care of obese people and ii) do it in full awareness of the obligatory postoperative clinical observation.

[Is there a role for surgery in the treatment of type 2 diabetes?]. / Welche Rolle spielt die Chirurgie bei der Therapie des Diabetes mellitus Typ 2?

Typ 2 diabetes mellitus (T2DM) can be regarded as a chronic and progressive disease which is rapidly increasing worldwide. There is a significant coincidence of T2DM and obesity, the latter playing a major role in the development of insulin resistance. Medical treatment comprises lifestyle counseling, weight management and an increased physical activity, frequently in combination with pharmacotherapy. However, especially in obese patients, metabolic aims are frequently not achieved which can be attributed to the lack of significant weight reduction. Currently, pancreas transplantation plays only a minor role in the treatment of patients with T2DM. Bariatric surgery has been proven to be a safe and effective therapeutic option in obese patients that leads to a significant weight loss. Moreover, in the majority of obese diabetics, a complete or partial remission of T2DM is observed. The significant weight loss is associated with improved insulin sensitivity. There is some evidence that alterations of gut hormones play an additional role in the amelioration of T2DM. However, little is known about the long-term effect of bariatric surgery on diabetes remission. Bariatric procedures should be considered in obese patients with T2DM (BMI > 35 kg/m²) and poorly controlled metabolic status. Despite the encouraging results in normal weight or overweight patients with T2DM, surgery can not yet be recommended in these patients. Intensive research about the impact of bariatric surgery on diabetes remission offers a unique opportunity to understand pathophysiology of T2DM. Furthermore, it may help to develop less invasive interventions and to identify new therapeutic targets for the treatment of T2DM.

Bariatric surgery in adolescents and young adults--safety and effectiveness in a cohort of 345 patients.

OBJECTIVE: To examine the safety and effectiveness of adolescent bariatric surgery and to improve treatment recommendations for this age group. DESIGN: Prospective longitudinal registry. Since January 2005, patients undergoing bariatric surgery in Germany are enlisted in an online registry called 'study for quality assurance in obesity surgeries'. SUBJECTS: Adolescents and young adults up to the age of 21 years, operated from January 2005 to December 2010. MEASUREMENTS: Weight, BMI, comorbidities, complication rates. RESULTS: N=345 primary procedures were recorded by 58 hospitals. N=51 patients were under the age of 18 years. Follow-up information was available for 48% (n=167) of patients, with an average observation period of 544±412 days (median: 388 days). The most common surgical techniques were gastric banding (n=118, 34.2%), gastric bypass (n=116, 33.6%) and sleeve gastrectomy (n=78, 22.6%). Short-term complications (intra-operative; general postoperative; specific postoperative) were slightly lower for gastric banding (0.8%; 2.5%; 0.8%) than for gastric bypass (2.6%; 5.2%; 1.7%) or sleeve gastrectomy (0%; 9.0%; 7.7%). In accordance with published findings, weight and BMI reduction were lower for gastric banding (-28 kg; -9.5 kg m(-2)) compared to gastric bypass (-50 kg; -16.4 kg m(-2)) P< 0.001 or sleeve gastrectomy (-46 kg; -15.4 kg m(-2)) P< 0.001. Outcomes did not differ between the <18 and ≥18-year-old patients. CONCLUSION: Like in adults, bariatric surgery has low short-term complication rates and results in sustained weight loss in adolescents. However, the missing long-term observations prohibit a final conclusion about lasting effectiveness and safety. Clinical trials with structured follow-up programs and mechanisms to ascertain patient adherences are needed.

[Increased requirements for the challenging abdominosurgical management of morbid obesity - what does the abdominal surgeon need to know?]. / Gewachsene Erfordernisse im anspruchsvollen viszeralchirurgischen Management bei morbider Adipositas - Was muss der Viszeralchirurg wissen?

In the international comparison and in Europe, the Federal Republic of Germany belongs to the countries with a very high prevalence of obesity (men, 67.1 %; women, 53 %). Among the European countries, the incidence of diabetes mellitus type 2 is also high ("Study of the health of adults in Germany" [DEGS]) - Robert Koch Institute). Not only for surgeons, this can be considered as a great challenge even in usual abdominosurgical interventions. 1. Surgical equipment needs to be adapted to the requirements for obese patients. 2. Minimally invasive surgery reduces not only complication rates with regard to postsurgical wound infection and hernia in such patients, it allows a competent assessment of the peritoneal cavity. 3. A great number of surgical tools and instruments can be used in normal weight as well as morbidly obese patients with no limitations - for conventional (open) surgical interventions, retractor systems should be available. 4. With regard to emergency surgery in patients who had formerly undergone bariatric surgery, a competent basic knowledge on the usual bariatric surgical interventions and the subsequent anatomic consequences as well as the more frequent mid- and long-term complications is necessary, which need to be partially approached with the surgical intervention. 5. For numerous oncosurgical interventions, no differences in postoperative outcome were found between normal weight and morbidly obese patients.

[New data on quality assurance in bariatric surgery in Germany]. / Aktuelle Daten der Qualitätssicherungsstudie für operative Therapie der Adipositas in Deutschland.

BACKGROUND: Since January 1st 2005, the situation of bariatric surgery has been examined in Germany. All data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University of Magdeburg. METHODS: The voluntary data registration occurs in an internet online data bank. All primary bariatric procedures as well as re- and redo-procedures are documented. Follow-up data were collected once a year. Participation in the quality assurance study is obligatory for certificated centres. RESULTS: Since 2005 13,879 bariatric procedures have been performed at 83 hospitals. The number of primary procedures has increased from 596 in 2005 to 11,835 in 2010. Revisional surgery has been performed in 1,438 patients since 2005. Sleeve gastrectomy (SG) is the major procedure with 1,564 operations in 2010. The mean BMI was 48.8 kg/m². The incidence of comorbidities was 84.8%. CONCLUSION: Bariatric surgery has become more accepted in Germany. Beside the Roux-en-Y gastric bypass, sleeve gastrectomy is the most frequently performed operation. BMI and incidence of comorbidities are still high in comparison with literature values. Due to the lack of evidence, more randomised studies are necessary to standardise operative techniques and evaluate patient selection criteria. Quality assurance studies support a detailed analysis of these parameters.