[Improvement of cost allocation in gastroenterology by introduction of a novel service catalogue covering the complete spectrum of endoscopic procedures]. / Verbesserung der Kostenkalkulation in der Gastroenterologie durch Einführung eines neuen Leistungskatalogs für alle endoskopischen Prozeduren.

BACKGROUND: The German hospital reimbursement system (G-DRG) is incomplete for endoscopic interventions and fails to differentiate between complex and simple procedures. This is caused by outdated methods of personnel-cost allocation. METHODS: To establish an up-to-date service catalogue 50 hospitals made their anonymized expense-budget data available to the German-Society-of-Gastroenterology (DGVS). 2.499.900 patient-datasets (2011-2013) were used to classify operation-and-procedure codes (OPS) into procedure-tiers (e.g. colonoscopy with biopsy/colonoscopy with stent-insertion). An expert panel ranked these tiers according to complexity and assigned estimates of physician time. From June to November 2014 exact time tracking data for a total 38.288 individual procedures were collected in 119 hospitals to validate this service catalogue. RESULTS: In this three-step process a catalogue of 97 procedure-tiers was established that covers 99% of endoscopic interventions performed in German hospitals and assigned validated mean personnel-costs using gastroscopy as standard. Previously, diagnostic colonoscopy had a relative personnel-cost value of 1.13 (compared to gastroscopy 1.0) and rose to 2.16, whereas diagnostic ERCP increased from 1.7 to 3.62, more appropriately reflecting complexity. Complex procedures previously not catalogued were now included (e.g. gastric endoscopic submucosal dissection: 16.74). DISCUSSION: This novel service catalogue for GI-endoscopy almost completely covers all endoscopic procedures performed in German hospitals and assigns relative personnel-cost values based on actual physician time logs. It is to be included in the national coding recommendation and should replace all prior inventories for cost distribution. The catalogue will contribute to a more objective cost allocation and hospital reimbursement - at least until time tracking for endoscopy becomes mandatory.

The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study.

OBJECTIVE: Hyperhomocysteinemia is a described risk factor of cardiovascular diseases. The aim of this study was the treatment of hyperhomocysteinemia in liver transplant recipients with L-5-methyltetrahydrofolate (L-5-MTHF; 1 mg) vs folic acid (1 mg) vs placebo in a double-blind placebo-controlled study and to compare the relative responsiveness of these patients to L-5-MTHF and folic acid. SUBJECTS/METHODS: Patients were recruited from Hepatology-Transplantation-Unit at Johann Wolfgang Goethe-University, Frankfurt. Sixty patients were included in this study and 12 patients dropped out for different reasons. The patients were treated over 8 weeks with supplemental L-5-MTHF or folic acid or placebo. Serum homocysteine (HCY) was analyzed with high-performance liquid chromatography (HPLC) beside routine lab tests. RESULTS: We observed only a significant decrease of total serum HCY in the L-5-MTHF group during the study period (at week 0: 15+/-7.7 microM; after 8 weeks treatment: 9.41+/-2.6 microM, P<0.001). There was no significant decrease of total serum HCY neither in the folic acid group nor in the placebo group. CONCLUSION: The effects of L-5-MTHF are significantly more potent than folic acid itself. Therefore, lowering serum HCY in liver transplant recipients is effective with L-5-MTHF.

Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation.

OBJECTIVE: The aim of this study was to evaluate the role of the C677T-MTHFR (methylenetetrahydrofolate reductase)-polymorphism (CC, CT and TT) for vascular complications in liver transplant recipients. DESIGN: Retrospective study. SETTING: Hepatology-Transplantation-Unit, Johann Wolfgang Goethe-University, Frankfurt am Main. SUBJECTS: 48 liver transplant recipients were included, no dropouts. METHODS: MTHFR polymorphism was detected by PCR amplification and digestion with Hinfl restriction enzyme. Vascular complications after liver transplantation were detected from the patients' records. The total serum homocysteine (HCY) was analyzed with high-pressure liquid chromatography. RESULTS: In the wild-type group (CC), the HCY levels were slightly high (14.0+/-1 micro M). Among the patients with the CT polymorphism, the HCY values were elevated (22.5+/-3 micro M). In the homozygous TT group, there was a significant increase (31.2+/-6 micro M, P<0.01) of the HCY values. The percentage of vascular complications was higher in the heterozygous CT (47%) and homozygous TT (62.5%) group compared with wild-type CC (21%). Patients with a homozygous TT genotype of the MTHFR polymorphism with a vascular complication had a highly significant elevated HCY level compared to the other genotype groups, both with and without any vascular complications (P<0.001). Recipients with an elevated HCY and the TT polymorphism have a higher probability of developing a vascular complication after transplantation (odds ratio: 4.3 and 11.0; 95% confidence interval: 1.15, 12.25 and 1.41, 85.24). CONCLUSIONS: The C677T polymorphism in the MTHFR gene and subsequent elevation of the total serum HCY is significantly associated with an increased incidence of vascular complications in liver transplant recipients.

Human peritoneal macrophages in culture: a model for studying inflammatory disorders in vitro.

In this study we characterized a model of human peritoneal macrophages maintained in culture for up to 48 h that can be used to study different functions of this cell population in vitro. The cells remained viable and functionally active over time, with well-preserved phagocytic properties. They expressed a macrophage marker, CD14. Once in culture, human peritoneal macrophages secreted C1q and nitric oxide in a pattern described in murine, guinea pig, and rat peritoneal macrophages. The described model can be used to study physiology and pathophysiology of peritoneal macrophages in vitro, offering all the advantages of the use of a human cell population.

Downregulation of the cyclin D1/Cdk4 complex occurs during resveratrol-induced cell cycle arrest in colon cancer cell lines.

Resveratrol is a naturally occurring polyphenol with cancer chemopreventive properties. The objective of the current study was to investigate the effect of resveratrol on the human colonic adenocarcinoma cell line Caco-2. The compound inhibited cell growth and proliferation of Caco-2 cells in a dose-dependent manner (12.5-200 micromol/L) as assessed by crystal violet assay, [(3)H]thymidine and [(14)C]leucine incorporation. Furthermore, apoptosis was determined by measuring caspase-3 activity, which increased significantly after 24 and 48 h of treatment with 200 micromol/L resveratrol. Perturbed cell cycle progression from the S to G2 phase was observed for concentrations up to 50 micromol/L, whereas higher concentrations led to reversal of the S phase arrest. These effects were specific for resveratrol; they were not observed after incubation with the stilbene analogs stilbenemethanol and rhapontin. Levels of cyclin D1 and cyclin-dependent kinase (cdk) 4 proteins were decreased, as revealed by immunoblotting. In addition, resveratrol enhanced the expression of cyclin E and cyclin A. The protein levels of cdk2, cdk6 and proliferating cell nuclear antigen were unaffected. Similar results were obtained for the colon carcinoma cell line HCT-116, indicating that cell cycle inhibition by resveratrol is independent of cyclooxygenase inhibition. The phosphorylation state of the retinoblastoma protein in Caco-2 cells was shifted from hyperphosphorylated to hypophosphorylated at 200 micromol/L, which may account for reversal of the S phase block at concentrations exceeding 50 micromol/L. These findings suggest that resveratrol exerts chemopreventive effects on colonic cancer cells by inhibition of the cell cycle.

HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2.

Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Butyrate, a short-chain fatty acid, reduces proliferation and induces differentiation of human colon cancer cells. The aim of our study was to determine the effect of mevastatin, alone or in combination with butyrate, on proliferation, the cell cycle and apoptosis in the human colorectal carcinoma cell line Caco-2. In this report we show that mevastatin combined with butyrate synergistically suppressed growth of Caco-2 cells in a dose- and time-dependent manner. In addition, incubation with mevastatin arrested cells in the G1 phase of the cell cycle after 24 h with a switch to the G2/M phase after 72 h. This was accompanied by a down-regulation of cyclin-dependent kinases (cdk) 4 and cdk 6 as well as cyclin D1, while cdk 2 and cyclin E protein levels remained unchanged during mevastatin treatment. Cell cycle inhibitors p21 and p27 were significantly upregulated by mevastatin. The proapoptotic properties of mevastatin were further enhanced by co-incubation with butyrate. Lastly, the effects of mevastatin could be reversed by addition of mevalonate, but not farnesyl- or geranylgeranylpyrophosphate, intermediate products of cholesterol synthesis, to the medium. These results suggest that HMG-CoA reductase inhibitors like mevastatin may enhance the antiproliferative effect of butyrate in colon cancer cells via induction of apoptosis together with a G0/G1 cell cycle arrest.