M Küper

Nutrition, Intestinal Permeability, and Blood Ethanol Levels Are Altered in Patients with Nonalcoholic Fatty Liver Disease (NAFLD)

BackgroundA role of an altered dietary pattern (e.g., a diet rich in sugar) but also alterations at the level of the intestinal barrier have repeatedly been discussed to be involved in the development and progression of nonalcoholic fatty liver disease (NAFLD).AimsTo determine if the nutritional intake, intestinal flora, and permeability and the development of NAFLD are related in humans.MethodsTen controls and 20 patients with NAFLD ranging from simple steatosis to steatohepatitis were included in the study. Bacterial overgrowth, orocecal transit time, and intestinal permeability were assessed. Alcohol, endotoxin, and plasminogen activator inhibitor (PAI-) 1 concentration were determined in plasma. Nutritional intake was assessed using a dietary history.ResultsDespite no differences in the prevalence of bacterial overgrowth and in the orocecal transit time, intestinal permeability, alcohol, and endotoxin levels in plasma were significantly higher in patients with NAFLD than in controls. Similar results were also found for PAI-1 plasma concentrations. Patients with NAFLD had a significantly higher intake of protein, total carbohydrates, and mono- as well as disaccharides than controls. PAI-1, endotoxin, and ALT plasma levels were positively related to total protein and carbohydrate intake.ConclusionsTaken together, our results indicate that intestinal permeability, endogenous alcohol synthesis, and nutritional intake are markedly altered in patients with NAFLD.

Transient Lower Esophageal Sphincter Relaxation in Morbid Obesity

BackgroundThere is strong evidence that morbid obesity is often accompanied by gastroesophageal reflux. Gastroesophageal reflux is caused predominantly by transient lower esophageal sphincter relaxations (TLESRs). Only few data are available about TLESRs in patients with stage III obesity (body mass index > 35). The aim of this study was to analyze the frequency and types of TLESRs in patients with morbid obesity in different physiological stages (postprandial: upright and recumband) compared to patients with normal weight gastroesophageal reflux disease (GERD) and diffuse esophagus spasm (DES).MethodsIn order to measure TLESRs in obese patients with and without GERD, three subgroups were prospectively performed: group I consisted of seven healthy controls, group II consisted of seven obese patients, group III consisted of seven non-obese patients with GERD, and in group IV, five patients were recruited with diffuse esophageal spasm. All participants underwent both conventional water-perfused stationary esophagus manometry and a 24-h ambulatory esophagus manometry, 24-h ambulatory pH monitoring, and esophago-gastroscopy. In order to measure the lower esophageal sphincter pressure (LESP) over a prolonged time under physiological conditions, a special solid-state sleeve catheter was used. Additionally, all patients were interviewed using a standardized questionnaire.ResultsCompared to normal subjects, patients with morbid obesity and patients with gastroesophageal reflux show a substantial increase of TLESRs in the postprandial phase. There was a tendency towards more TLESRs per hour in patients with DES than in healthy subjects, but the difference was not statistically significant. The types of TLESRs differed with the LESP. The majority of isolated TLESRs were complete and incomplete. Some of the isolated TLESRs were accompanied by contractions of the tubular esophagus.ConclusionMorbid obesity is associated with gastroesophageal reflux. The frequency of TLESRs has significantly increased compared to healthy subjects and does not differ statistically from patients with GERD. Isolated TLESRs are mostly incomplete in patients with a hypotonic LES.

Fifty percent area reduction after 4 weeks of treatment is a reliable indicator for healing : analysis of a single-center cohort of 704 diabetic patients

INTRODUCTION The aim of the study was to investigate whether an area reduction greater than 50% within the first 4 weeks of treatment is associated with a higher long-term probability of healing. PATIENTS AND METHODS We treated diabetic foot ulcers according to a comprehensive interdisciplinary wound care protocol. Follow-up was documented through a special wound documentation system. Data were entered into SPSS for statistical analysis to calculate the probability of healing according to the Kaplan-Meier method. Results were expressed as median (minimum-maximum), and the percentage of area reduction (PA) was defined as [(area(4 weeks)/area(baseline))x100)/area(baseline). Patients were divided into responders when PA reached at least 50% and nonresponders when PA was less than 50%. Healing was defined as PA=100%. RESULTS In total, 704 patients were included into the analysis. Median time of follow-up was 71 (2-365) days. Wound duration was 31 (1-4018) days, and the initial wound size was calculated to be 1.18 (0.1-99) cm(2). In 27.8%, there was a positive probing to bone; in 64.5%, both pedal pulses were not palpable. Major amputation rate was 2.8% and minor amputation rate was 10.2%. The overall probability of healing was 35% after 12 weeks, 41% after 16 weeks, and 73% after 1 year. The surrogate visit (4 weeks) was performed after a median of 27 (14-42) days without a difference between responders and nonresponders. There were 334 (47%) responders and 370 (53%) nonresponders. Responders had a significantly higher probability of healing compared with nonresponders (12 weeks: 52.3% vs. 18.4%, P=.0001; 16 weeks: 46.7% vs. 26.5%, P=.0001; 1 year: 82.5% vs. 64.9%, P=.0001). CONCLUSIONS The calculation of the percentage of area reduction after 4 weeks of treatment is a valid tool to estimate the probability of healing. In clinical practice, a reevaluation of the treatment schedule is recommended for wounds that do not reach 50% area reduction within the first 4 weeks of therapy.

Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients

Objective:Sensing of nutrients in the stomach is of crucial importance for the regulation of ingestive behavior especially in the context of metabolic dysfunctions such as obesity. Cells in the gastric mucosa with taste-signaling elements are considered as candidates for sensing the composition of ingested food and consequently modulate gastrointestinal processes. To assess whether obesity might have an impact on gastric chemosensory cells, gastric tissue samples from morbidly obese patients and normal-weight subjects were compared using a reverse transcriptase (RT)-PCR, qPCR and immunohistochemical approach.Results:Analysis of biopsy tissue samples from human stomach revealed that transcripts for the taste-signaling elements, including the receptor T1R3 involved in the reception of amino acids and carbohydrates, the fatty acid receptor GPR120, the G protein gustducin, the effector enzyme PLCβ2 and the ion channel TRPM5 are present in the human gastric mucosa and led to the visualization of candidate chemosensory cells in the stomach expressing gustatory marker molecules. RT-PCR and qPCR analyses indicated striking differences in the expression profiles of specimens from obese subjects compared with controls. For GPR120, gustducin, PLCβ2 and TRPM5 the expression levels were increased, whereas for T1R3 the level decreased. Using TRPM5 as an example, we found that the higher expression level was associated with a higher number of TRPM5 cells in gastric tissue samples from obese patients. This remarkable change was accompanied by an increased number of ghrelin-positive cells.Conclusions:Our findings argue for a relationship between the amount of food intake and/or the energy status and the number of candidate chemosensory cells in the gastric mucosa.

Impact of protein supplementation after bariatric surgery: A randomized controlled double-blind pilot study

OBJECTIVES Bariatric patients are at risk of protein deficiency. The aim of this study was to determine possible benefits of postoperative protein supplementation weight reduction, body composition, and protein status. METHODS Twenty obese patients who underwent bariatric surgery were randomized either to the protein (PRO) group, which received a daily protein supplement over 6 months postoperatively, or to the control (CON) group, which received an isocaloric placebo in a double-blind fashion. Data on protein and energy intake, body weight, body composition, blood proteins, and grip force was collected preinterventionally and at 1, 3, and 6 months postoperatively. RESULTS In both groups body weight was significantly reduced to a similar extent (after 6 months: PRO group 25.4 ± 7.2%, CON group 20.9 ± 3.9%; intergroup comparison P > 0.05). Protein intake was steadily increased in the PRO group, but not in the CON group, and reached maximum at month 6 (25.4 ± 3.7% of energy intake versus 15.8 ± 4.4%; P < 0.001). In the PRO group, body fat mass loss was higher than that in the CON group (79% of absolute weight loss versus 73%; P = 0.02) while lean body mass loss was less pronounced (21% versus 27%, P = 0.05). Blood proteins and grip force did not differ at any time point between the two groups. CONCLUSIONS The present study suggests that protein supplementation after bariatric surgery improves body composition by enhancing loss of body fat mass and reducing loss of lean body mass within the 6 months follow up.

Multichannel Intraluminal Impedance Measurement of Gastroesophageal Reflux in Patients with Different Stages of Morbid Obesity

BackgroundObesity is now one of the world’s major chronic diseases. The etiology of the severe comorbid conditions associated with morbid obesity is not fully understood, and in particular the relationship between gastroesophageal reflux and obesity.MethodsSixty-seven patients were enrolled in this prospective study. Patients and control individuals were divided into four subgroups according to their body mass index (BMI). Esophageal motility was assessed using a conventional water-perfused esophageal manometry catheter, and 24-h pH-metry was carried out using multichannel intraluminal impedance equipment.ResultsIn the group with the highest BMI (>50), contraction amplitudes in the middle and distal esophagus were significantly higher in comparison both with the control group and groups with a lower BMI (P < 0.05). Lower esophageal sphincter pressure was reduced in the majority of patients with morbid obesity and differed significantly from the control group (P < 0.001). Significant differences between the control group and the patient groups were also observed on 24-h pH-metry (P < 0.05). The 24-h impedance measurements distinguished between acid and nonacid status and between the upright and recumbent positions. The total number of reflux episodes differed significantly between the control and patient groups and between groups III and IV, with lower and higher BMI values (P < 0.008 and P < 0.05, respectively).ConclusionsThe impedance data obtained in this study confirm that patients with morbid obesity are at risk of developing gastroesophageal reflux disease. However, there is no evidence of a direct correlation between the severity of reflux and the extent of obesity.

M.A.I.D.: a prognostic score estimating probability of healing in chronic lower extremity wounds.

Objective:To evaluate a wound-based prognostic score for chronic lower extremity wounds suitable for daily routine use capable of predicting long-term healing. Summary Background Data:The main obstacle in the treatment of chronic wounds is to estimate long-term clinical outcome. For diabetic foot ulcers, several ulcer, and nonulcer-related risk factors associated with impaired healing have been described in the past. Methods:A new chronic lower extremity ulcer score (M.A.I.D.) was created out of 4 clinically defined parameters, namely palpable pedal pulses (I), wound area (A), ulcer duration (D), and presence of multiple ulcerations (M). Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while wounds >4 cm2 were scored as 1 and wounds ≤4 cm2 as 0. Ulcers lasting more than 130 days were categorized as 1 and wounds with a duration of <130 days as 0. Patients with multiple ulcerations were graded as 1 (=1) compared with those with single ulcers (=0). M.A.I.D. was calculated by adding these separate scores to a theoretical maximum of 4. Results:Two thousand nineteen consecutive patients with 4004 wounds were included. When patients were divided into subgroups with the same M.A.I.D., we showed a decreasing probability of healing for ulcers with higher M.A.I.D. scores. An increase in the M.A.I.D. by 1 score-point reduced the chance for healing by 37%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the occurrence of soft-tissue infection during follow-up. Conclusions:This new chronic lower extremity ulcer score is capable of anticipating long-term probability of healing by combining 4 clinically assessable parameters. However, adequate and standardized wound care is an indispensable prerequisite for M.A.I.D. to be a valid diagnostic tool in daily clinical routine.

Everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses.

BACKGROUND Delayed wound healing is a serious side effect of mTOR inhibitor-based immunosuppression after solid organ transplantation. The aim of this study was to test the hypothesis that the mTOR inhibitor everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses. MATERIALS AND METHODS Thirty male Sprague-Dawley rats received a colonic anastomosis. Then, animals were randomized to three groups of daily treatment with either vehicle or everolimus in two different dosages (1.0mg/kg or 3.0mg/kg). After 7 d, rats were sacrificed, and mechanical, histologic, and biochemical parameters of intestinal healing were assessed. RESULTS Anastomotic bursting pressure was significantly decreased by everolimus in both dosages, whereas hydroxyproline content was reduced only by the high everolimus dosage. Everolimus diminished cellular proliferation and new vessel growth. Furthermore, both quantity as well as quality of newly synthesized collagen fibers in the anastomotic granulation tissue was reduced. On the other hand, myeloperoxidase-positive (MPO) cells and interleukin-6 (IL-6) concentrations were increased, as was the activity of matrix-metalloproteinases MMP-2 and MMP-9. CONCLUSION Everolimus interferes with the inflammatory phase of healing. However, it remains unclear whether this phenomenon is involved in everolimus impairment of experimental anastomotic repair.

Laparoscopic surgery for benign and malign diseases of the digestive system: indications, limitations, and evidence.

The laparoscopic technique was introduced in gastrointestinal surgery in the mid 1980s. Since then, the development of this technique has been extraordinary. Triggered by technical innovations (stapling devices or coagulation/dissecting devices), nowadays any type of gastrointestinal resection has been successfully performed laparoscopically and can be performed laparoscopically dependent on the patients condition. This summary gives an overview over 30 years of laparoscopic surgery with focus on todays indications and evidence. Main indications remain the more common procedures, e.g., appendectomy, cholecystectomy, bariatric procedures or colorectal resections. For all these indications, the laparoscopic approach has become the gold standard with less perioperative morbidity. Regarding oncological outcome there have been several high-quality randomized controlled trials which demonstrated equivalency between laparoscopic and open colorectal resections. Less common procedures like esophagectomy, oncological gastrectomy, liver and pancreatic resections can be performed successfully as well by an experienced surgeon. However, the evidence for these special indications is poor and a general recommendation cannot be given. In conclusion, laparoscopic surgery has revolutionized the field of gastrointestinal surgery by reducing perioperative morbidity without disregarding surgical principles especially in oncological surgery.

Immunonutrition with Long-Chain Fatty Acids Prevents Activation of Macrophages in the Gut Wall

BackgroundImmune cells and inflammatory mediators are released from the gastrointestinal tract into the mesenteric lymph during sepsis causing distant organ dysfunction. Recently, it was demonstrated that macrophages in the gut wall are controlled by the vagus nerve, the so-called cholinergic anti-inflammatory pathway.AimThis study aims to investigate whether an enteral diet with lipid prevents the activation of leukocytes in the gut wall.MethodsMesenteric lymph was obtained from rats, receiving an enteral infusion of glucose or glucose + lipid before and after lipopolysaccharide (LPS) injection. Immune cells in mesenteric lymph were analyzed with fluorescence-activated cell sorting before and after LPS injection. Mesenteric lymph leukocytes from rats receiving enteral glucose with or without lipid were stimulated in vitro with LPS and tumor necrosis factor (TNF)α was measured in the supernatant.ResultsThe release of macrophages from the gut during sepsis was not significantly different in animals enterally treated with glucose or lipid. However, the release of TNFα from mesenteric lymph leukocytes after in vitro LPS stimulation was more than 3-fold higher in the glucose group compared to the lipid-treated group.ConclusionsDuring sepsis, activated macrophages are released from the gut into mesenteric lymph. However, an enteral diet with lipid is able to suppress the inflammatory cytokine release from mesenteric lymph leukocytes.