How do patients' clinical phenotype and the physiological mechanisms of the operations impact the choice of bariatric procedure?

Bariatric surgery is currently the most effective option for the treatment of morbid obesity and its associated comorbidities. Recent clinical and experimental findings have challenged the role of mechanical restriction and caloric malabsorption as the main mechanisms for weight loss and health benefits. Instead, other mechanisms including increased levels of satiety gut hormones, altered gut microbiota, changes in bile acid metabolism, and/or energy expenditure have been proposed as explanations for benefits of bariatric surgery. Beside the standard proximal Roux-en-Y gastric bypass and the biliopancreatic diversion with or without duodenal switch, where parts of the small intestine are excluded from contact with nutrients, resectional techniques like the sleeve gastrectomy (SG) have recently been added to the armory of bariatric surgeons. The variation of weight loss and glycemic control is vast between but also within different bariatric operations. We surveyed members of the Swiss Society for the Study of Morbid Obesity and Metabolic Disorders to assess the extent to which the phenotype of patients influences the choice of bariatric procedure. Swiss bariatric surgeons preferred Roux-en-Y gastric bypass and SG for patients with type 2 diabetes mellitus and patients with a body mass index >50 kg/m(2), which is consistent with the literature. An SG was preferred in patients with a high anesthetic risk or previous laparotomy. The surgeons' own experience was a major determinant as there is little evidence in the literature for this approach. Although trends will come and go, evidence-based medicine requires a rigorous examination of the proof to inform clinical practice

Innate sensing of chitin and chitosan

Chitin is the second most common polysaccharide found in nature. It is present in crustacean shells, insect exoskeletons, parasitic nematode eggs and gut linings, and in the cell wall of fungi. The deacetylated derivative of chitin, chitosan, is less common but is particularly evident in certain species of fungi, such as Cryptococcus, and the cyst wall of Entamoeba. How mammals sense and respond to these polymers is not well understood, and conflicting reports on their immunological activity have led to some controversy. Despite this, promising translational applications that exploit the unique properties of chitin and chitosan are being developed

Chirurgie als pluripotentes Instrument gegen eine metabolische Erkrankung: Was sind die Mechanismen?

Zusammenfassung: Die bariatrische/metabolische Chirurgie stellt derzeit die effektivste Therapie zur dauerhaften Gewichtsreduktion und Verbesserung der mit Adipositas assoziierten metabolischen Begleiterkrankungen wie Diabetes mellitus Typ 2, arterielle Hypertonie, Lipidstoffwechselstörungen und kardiovaskuläre Erkrankungen dar. Trotz kontinuierlich steigender Operationszahlen in Deutschland und weltweit sowie belegter Effektivität sind die genauen Wirkmechanismen der Operationsverfahren jedoch nicht vollständig geklärt. Einer der am häufigsten durchgeführten und am besten untersuchten Eingriffe ist der Roux-en-Y-Magenbypass (RYGB), dessen Wirksamkeit traditionell durch mechanische Nahrungsrestriktion und kalorische Malabsorption begründet wurde. Inzwischen hat sich allerdings gezeigt, dass die zugrunde liegenden Mechanismen weitaus komplexer sind und dass physiologische Prozesse wie beispielsweise veränderte Spiegel verschiedener gastrointestinaler Hormone, ein gesteigerter Energieumsatz und eine modifizierte Zusammensetzung des intestinalen Mikrobioms eine wichtigere Rolle spielen. Nachdem die Verbesserung der metabolischen Begleiterkrankungen lange Zeit als Folgeeffekt der Gewichtsreduktion nach RYGB interpretiert wurde, hat sich inzwischen gezeigt, dass dies zumindest teilweise gewichtsunabhängig zu sein scheint und direkt durch physiologische Veränderungen vermittelt wird. Dieser Artikel soll eine Übersicht zu den potenziellen und aktuell wichtigsten Wirkmechanismen der RYGB-Operation liefern, die sowohl an der Therapie des Übergewichts als auch der adipositasassoziierten metabolischen Begleiterkrankungen beteiligt sind

Chirurgie als pluripotentes Instrument gegen eine metabolische Erkrankung

Die bariatrische/metabolische Chirurgie stellt derzeit die effektivste Therapie zur dauerhaften Gewichtsreduktion und Verbesserung der mit Adipositas assoziierten metabolischen Begleiterkrankungen wie Diabetes mellitus Typ 2, arterielle Hypertonie, Lipidstoffwechselstörungen und kardiovaskuläre Erkrankungen dar. Trotz kontinuierlich steigender Operationszahlen in Deutschland und weltweit sowie belegter Effektivität sind die genauen Wirkmechanismen der Operationsverfahren jedoch nicht vollständig geklärt. Einer der am häufigsten durchgeführten und am besten untersuchten Eingriffe ist der Roux-en-Y-Magenbypass (RYGB), dessen Wirksamkeit traditionell durch mechanische Nahrungsrestriktion und kalorische Malabsorption begründet wurde. Inzwischen hat sich allerdings gezeigt, dass die zugrunde liegenden Mechanismen weitaus komplexer sind und dass physiologische Prozesse wie beispielsweise veränderte Spiegel verschiedener gastrointestinaler Hormone, ein gesteigerter Energieumsatz und eine modifizierte Zusammensetzung des intestinalen Mikrobioms eine wichtigere Rolle spielen. Nachdem die Verbesserung der metabolischen Begleiterkrankungen lange Zeit als Folgeeffekt der Gewichtsreduktion nach RYGB interpretiert wurde, hat sich inzwischen gezeigt, dass dies zumindest teilweise gewichtsunabhängig zu sein scheint und direkt durch physiologische Veränderungen vermittelt wird. Dieser Artikel soll eine Übersicht zu den potenziellen und aktuell wichtigsten Wirkmechanismen der RYGB-Operation liefern, die sowohl an der Therapie des Übergewichts als auch der adipositasassoziierten metabolischen Begleiterkrankungen beteiligt sind

Diagnostic performance of CT with Valsalva maneuver for the diagnosis and characterization of inguinal hernias

PURPOSE Inguinal hernias are mainly diagnosed clinically, but imaging can aid in equivocal cases or for treatment planning. The purpose of this study was to evaluate the diagnostic performance of CT with Valsalva maneuver for the diagnosis and characterization of inguinal hernias. METHODS This single-center retrospective study reviewed all consecutive Valsalva-CT studies between 2018 and 2019. A composite clinical reference standard including surgery was used. Three blinded, independent readers (readers 1-3) reviewed the CT images and scored the presence and type of inguinal hernia. A fourth reader measured hernia size. Interreader agreement was quantified with Krippendorff's α coefficients. Sensitivity, specificity, and accuracy of Valsalva-CT for the detection of inguinal hernias was computed for each reader. RESULTS The final study population included 351 patients (99 women) with median age 52.2 years (interquartile range (IQR), 47.2, 68.9). A total of 381 inguinal hernias were present in 221 patients. Sensitivity, specificity, and accuracy were 85.8%, 98.1%, and 91.5% for reader 1, 72.7%, 92.5%, and 81.8% for reader 2, and 68.2%, 96.3%, and 81.1% for reader 3. Hernia neck size was significantly larger in cases correctly detected by all three readers (19.0 mm, IQR 13, 25), compared to those missed by all readers (7.0 mm, IQR, 5, 9; p < 0.001). Interreader agreement was substantial (α = 0.723) for the diagnosis of hernia and moderate (α = 0.522) for the type of hernia. CONCLUSION Valsalva-CT shows very high specificity and high accuracy for the diagnosis of inguinal hernia. Sensitivity is only moderate which is associated with missed smaller hernias

Chitosan but not chitin activates the inflammasome by a mechanism dependent upon phagocytosis

Chitin is an abundant polysaccharide found in fungal cell walls, crustacean shells, and insect exoskeletons. The immunological properties of both chitin and its deacetylated derivative chitosan are of relevance because of frequent natural exposure and their use in medical applications. Depending on the preparation studied and the end point measured, these compounds have been reported to induce allergic responses, inflammatory responses, or no response at all. We prepared highly purified chitosan and chitin and examined the capacity of these glycans to stimulate murine macrophages to release the inflammasome-associated cytokine IL-1beta. We found that although chitosan was a potent NLRP3 inflammasome activator, acetylation of the chitosan to chitin resulted in a near total loss of activity. The size of the chitosan particles played an important role, with small particles eliciting the greatest activity. An inverse relationship between size and stimulatory activity was demonstrated using chitosan passed through size exclusion filters as well as with chitosan-coated beads of defined size. Partial digestion of chitosan with pepsin resulted in a larger fraction of small phagocytosable particles and more potent inflammasome activity. Inhibition of phagocytosis with cytochalasin D abolished the IL-1beta stimulatory activity of chitosan, offering an explanation for why the largest particles were nearly devoid of activity. Thus, the deacetylated polysaccharide chitosan potently activates the NLRP3 inflammasome in a phagocytosis-dependent manner. In contrast, chitin is relatively inert

Microstructural Changes in Human Ingestive Behavior After Roux-en-Y Gastric Bypass During Liquid Meals

BACKGROUND. Roux-en-Y gastric bypass (RYGB) decreases energy intake and is, therefore, an effective treatment of obesity. The behavioral bases of the decreased calorie intake remain to be elucidated. We applied the methodology of microstructural analysis of meal intake to establish the behavioral features of ingestion in an effort to discern the various controls of feeding as a function of RYGB. METHODS. The ingestive microstructure of a standardized liquid meal in a cohort of 11 RYGB patients, in 10 patients with obesity, and in 10 healthy-weight adults was prospectively assessed from baseline to 1 year with a custom-designed drinkometer. Statistics were performed on log-transformed ratios of change from baseline so that each participant served as their own control, and proportional increases and decreases were numerically symmetrical. Data-driven (3 seconds) and additional burst pause criteria (1 and 5 seconds) were used. RESULTS. At baseline, the mean meal size (909.2 versus 557.6 kCal), burst size (28.8 versus 17.6 mL), and meal duration (433 versus 381 seconds) differed between RYGB patients and healthy-weight controls, whereas suck volume (5.2 versus 4.6 mL) and number of bursts (19.7 versus 20.1) were comparable. At 1 year, the ingestive differences between the RYGB and healthy-weight groups disappeared due to significantly decreased burst size (P = 0.008) and meal duration (P = 0.034) after RYGB. The first-minute intake also decreased after RYGB (P = 0.022). CONCLUSION. RYGB induced dynamic changes in ingestive behavior over the first postoperative year. While the eating pattern of controls remained stable, RYGB patients reduced their meal size by decreasing burst size and meal duration, suggesting that increased postingestive sensibility may mediate postbariatric ingestive behavior. TRIAL REGISTRATION. NCT03747445; https://clinicaltrials.gov/ct2/show/NCT03747445. FUNDING. This work was supported by the University of Zurich, the Swiss National Fund (32003B_182309), and the Olga Mayenfisch Foundation. Bálint File was supported by the Hungarian Brain Research Program Grant (grant no. 2017-1.2.1-NKP-2017-00002)

Safety and effectiveness of bariatric surgery: Roux-en-Y gastric bypass is superior to gastric banding in the management of morbidly obese patients

<p>Abstract</p> <p>Background</p> <p>The use of bariatric surgery in the management of morbid obesity is rapidly increasing. The two most frequently performed procedures are laparoscopic Roux-en-Y bypass and laparoscopic gastric banding. The objective of this short overview is to provide a critical appraisal of the most relevant scientific evidence comparing laparoscopic gastric banding versus laparoscopic Roux-en-Y bypass in the treatment of morbidly obese patients.</p> <p>Results and discussion</p> <p>There is mounting and convincing evidence that laparoscopic gastric banding is suboptimal at best in the management of morbid obesity. Although short-term morbidity is low and hospital length of stay is short, the rates of long-term complications and band removals are high, and failure to lose weight after laparoscopic gastric banding is prevalent.</p> <p>Conclusion</p> <p>The placement of a gastric band appears to be a disservice to many morbidly obese patients and therefore, in the current culture of evidence based medicine, the prevalent use of laparoscopic gastric banding can no longer be justified. Based on the current scientific literature, the laparoscopic gastric bypass should be considered the treatment of choice in the management of morbidly obese patients.</p

Comparative effects of intraduodenal amino acid infusions on food intake and gut hormone release in healthy males

In contrast to the many studies of the effects of individual amino acids (AAs) on eating, no studies have compared the effects of different AAs on eating and underlying preabsorptive gastrointestinal mechanisms. To compare the effects of intraduodenal infusions of l-tryptophan (TRP), l-leucine (LEU), l-phenylalanine (PHE) and l-glutamine (GLN) on appetite, gastrointestinal hormone responses (including ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 [GLP-1]), glycemia (glucagon, insulin and glucose) and test meal size in healthy males, we retrospectively analyzed data from four published independent, randomized, double-blind, placebo-controlled studies of 90-min intraduodenal infusions of the individual AAs. The designs of the studies were identical, except the dose of TRP (0.15 kcal/min) was lower than that of the other AAs (0.45 kcal/min) because higher doses of this AA were not well tolerated. TRP and LEU decreased intake more than PHE (reductions relative to control, ~219 ± 68, ~170 ± 48 and ~12 ± 57 kcal, respectively), and TRP decreased intake more than GLN (~31 ± 82 kcal). These effects of TRP and LEU versus GLN, but not versus PHE, were paralleled by greater decreases in plasma ghrelin, and increases in CCK, concentrations. TRP increased PYY more than GLN or LEU, but not PHE. LEU increased PYY less than PHE. No significant differences were detected for GLP-1. PHE increased glucagon more than TRP or LEU, and increased insulin more than TRP. Under our experimental conditions, intraduodenal TRP and LEU were more satiating than PHE and GLN. The greater satiating efficacy of LEU versus PHE was significantly dissociated from the effects of these AAs on PYY, while the greater satiating potency of TRP versus PHE was significantly dissociated from the effects of these AAs on insulin and glucagon. In contrast, ghrelin and CCK, and potentially other mechanisms, including central sensing of individual AAs, appear to be stronger candidate mechanisms for the relative satiating effects obtained.Robert E. Steinert, Sina S. Ullrich, Nori Geary, Lori Asarian, Marco Bueter, Michael Horowitz, Christine Feinle-Bisse