Underfunding of German university-based high-performance medicine exemplified by the treatment of varices in cirrhosis.

Facing increasing economization in the health care sector, clinicians have to adapt not only to the ever-growing economic challenges, but also to a patient-oriented health care. Treatment costs are the most important variable for optimizing success when facing scarce human resources, increasing material- and infrastructure costs in general, as well as low revenue flexibility due to flat rates per case in Germany, the so-called Diagnosis-Related Groups (DRG). University hospitals treat many patients with particularly serious illnesses. Therefore, their share of complex and expensive treatments, such as liver cirrhosis, is significantly higher. The resulting costs are not adequately reflected in the DRG flat rate per case, which is based on an average calculation across all hospitals, which increases this economic pressure. Thus, the aim of this manuscript is to review cost and revenue structures of the management of varices in patients with cirrhosis at a university center with a focus on hepatology. For this monocentric study, the data of 851 patients, treated at the Gastroenterology Department of a University Hospital between 2016 and 2020, were evaluated retrospectively and anonymously. Medical services (e.g., endoscopy, radiology, laboratory diagnostics) were analyzed within the framework of activity-based-costing. As part of the cost unit accounting, the individual steps of the treatment pathways of the 851 patients were monetarily evaluated with corresponding applicable service catalogs and compared with the revenue shares of the cost center and cost element matrix of the German (G-) DRG system. This study examines whether university-based high-performance medicine is efficient and cost-covering within the framework of the G-DRG system. We demonstrate a dramatic underfunding of the management of varicose veins in cirrhosis in our university center. It is therefore generally questionable whether and to what extent an adequate care for this patient collective is reflected in the G-DRG system.

[Cost-efficiency of ascites treatment in the G-DRG system]. / Kosteneffizienz der Behandlung von Aszites bei Leberzirrhose im Rahmen des G-DRG-Systems.

In Germany, around 1,000,000 people are affected by cirrhosis of the liver, with ascites being a common consequence. Hospitals are caught between the opposing aims of profitability and patient-centered treatment as a result of the increasing compression of services in hospitals and the increasing economization in the healthcare sector. Treatment costs are a crucial starting point for optimizing success and the optimal use of resources, given the restricted revenue flexibility due to established flat charges per case. The goal of this study is to examine the exact cost and income structures for ascites therapy at a university hospital that specializes in liver diseases. The treatment data of 778 patients admitted to the University Hospital Aachen's Department of Internal Medicine III between 2016 and 2019 were retrospectively and anonymously evaluated for this study. The revenue shares of the matrix of cost centers and cost types of the German Diagnosis-Related Groups (G-DRG) system were compared to the revenue shares of the specified services in the context of activity-based costing. Inadequate refinancing was discovered in every area of the therapy process that was investigated. As a result, the treatment of ascites in cirrhosis is currently underrepresented in the DRG system. This is owing to the fact that patients treated at the university hospital have a greater case severity.

Ring Trial on Quantitative Assessment of Bile Acids Reveals a Method- and Analyte-Specific Accuracy and Reproducibility.

Bile acids are a key mediator of the molecular microbiome-host interaction, and various mass spectrometry-based assays have been developed in the recent decade to quantify a wide range of bile acids. We compare existing methodologies to harmonize them. Methodology for absolute quantification of bile acids from six laboratories in Europe were compared for the quantification of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) and conjugated products glycocholic acid (GCA) and taurocholic acid (TCA). For the bacterially modified secondary bile acids, the quantification of deoxycholic acid (DCA) and lithocholic acid (LCA) was compared. For the murine bile acids, we used the primary muricholic acids (α-MCA and, ß-MCA) and the intestinally produced secondary bile acid muricholic (ω-MCA). The standards were spiked into methanol:water (1:1) mix as well as in human and murine serum at either low concentration range (150-3000 nM) or high concentration range (1500-40,000 nM). The precision was better for higher concentrations. Measurements for the hydrophobic unconjugated bile acids LCA and ω-MCA were the most challenging. The quality assessments were generally very similar, and the comprehensive analyses demonstrated that data from chosen locations can be used for comparisons between studies.

Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. METHODS: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. RESULTS: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. CONCLUSIONS: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. LAY SUMMARY: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.

Comparison of non-invasive assessment of liver fibrosis in patients with alpha1-antitrypsin deficiency using magnetic resonance elastography (MRE), acoustic radiation force impulse (ARFI) Quantification, and 2D-shear wave elastography (2D-SWE).

PURPOSE: Although it has been known for decades that patients with alpha1-antitrypsin deficiency (AATD) have an increased risk of cirrhosis and hepatocellular carcinoma, limited data exist on non-invasive imaging-based methods for assessing liver fibrosis such as magnetic resonance elastography (MRE) and acoustic radiation force impulse (ARFI) quantification, and no data exist on 2D-shear wave elastography (2D-SWE). Therefore, the purpose of this study is to evaluate and compare the applicability of different elastography methods for the assessment of AATD-related liver fibrosis. METHODS: Fifteen clinically asymptomatic AATD patients (11 homozygous PiZZ, 4 heterozygous PiMZ) and 16 matched healthy volunteers were examined using MRE and ARFI quantification. Additionally, patients were examined with 2D-SWE. RESULTS: A high correlation is evident for the shear wave speed (SWS) determined with different elastography methods in AATD patients: 2D-SWE/MRE, ARFI quantification/2D-SWE, and ARFI quantification/MRE (R = 0.8587, 0.7425, and 0.6914, respectively; P≤0.0089). Four AATD patients with pathologically increased SWS were consistently identified with all three methods-MRE, ARFI quantification, and 2D-SWE. CONCLUSION: The high correlation and consistent identification of patients with pathologically increased SWS using MRE, ARFI quantification, and 2D-SWE suggest that elastography has the potential to become a suitable imaging tool for the assessment of AATD-related liver fibrosis. These promising results provide motivation for further investigation of non-invasive assessment of AATD-related liver fibrosis using elastography.

Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting.

A promising approach to treating obesity is to increase diet-induced thermogenesis in brown adipose tissue (BAT), but the regulation of this process remains unclear. Here we find that CDC-like kinase 2 (CLK2) is expressed in BAT and upregulated upon refeeding. Mice lacking CLK2 in adipose tissue exhibit exacerbated obesity and decreased energy expenditure during high-fat diet intermittent fasting. Additionally, tissue oxygen consumption and protein levels of UCP1 are reduced in CLK2-deficient BAT. Phosphorylation of CREB, a transcriptional activator of UCP1, is markedly decreased in BAT cells lacking CLK2 due to enhanced CREB dephosphorylation. Mechanistically, CREB dephosphorylation is rescued by the inhibition of PP2A, a phosphatase that targets CREB. Our results suggest that CLK2 is a regulatory component of diet-induced thermogenesis in BAT through increased CREB-dependent expression of UCP1.

Analysis of drug-related problems in three departments of a German University hospital.

BACKGROUND: During the last decades, pharmaceutical care services have been developed and implemented to optimize drug therapies and ensure medication safety. To investigate the need for pharmaceutical care services, drug-related problems can be measured. OBJECTIVE: Thus, the aim of this study was to analyse number, type and occurrence of drug-related problems in different clinical departments. SETTING: A pharmaceutical care service was established on general wards in Urology, Neurology and Gastroenterology at the University Hospital RWTH Aachen, Germany. METHOD: For each of a total of 306 patients, a pharmacist conducted an extended medication history, performed medication reconciliation, conducted medication safety checks and if drug-related problems were discovered, gave valid recommendations to the attending healthcare team. Drug-related problems were classified using the APS-Doc system. For statistical analyses, SAS(®) 9.1.3, SAS Institute, Cary NC, USA was applied. The project was approved by the local ethics committee. MAIN OUTCOME MEASURE: Type, occurrence and frequency of DRP in different medical departments. RESULTS: On average, 2.3 drug-related problems per patient were documented for all three departments. Drug-related problems were found in each category of the APS-Doc system. The most pronounced drug-related problems found were drug-drug interactions (34.6 %). 37 % of the identified drug-related problems occurred before hospital admission, 27 % during transitional care, and 36 % on the ward. Subgroup analysis revealed specific drug-related problem patterns for each clinical department. The number of drug-related problems was found to be associated with the number of drugs and age. CONCLUSION: Drug-related problems frequently occur in all investigated clinical departments. A holistic pharmaceutical care service could be an option to address this issue. In case of limited resources, individual drug-related problem patterns can be used as a basis for a tailored pharmaceutical care service. As number of drugs and age have been shown to be significant risk factors, it is crucial that the healthcare team including the pharmacist pays special attention to elderly patients and those with polymedication.

Diagnostic accuracy of diffusion-weighted magnetic resonance imaging versus positron emission tomography/computed tomography for early response assessment of liver metastases to Y90-radioembolization.

OBJECTIVES: Patients with hepatic metastases who are candidates for Y90-radioembolization (Y90-RE) usually have advanced tumor stages with involvement of both liver lobes. Per current guidelines, these patients have usually undergone several cycles of potentially hepatotoxic systemic chemotherapy before Y90-RE is at all considered, requiring split (lobar) treatment sessions to reduce hepatic toxicity. Assessing response to Y90-RE early, that is, already after the first lobar session, would be helpful to avoid an ineffective and potentially hepatotoxic second lobar treatment. We investigated the accuracy with which diffusion- weighted magnetic resonance imaging (DWI-MRI) and positron emission tomography/computed tomography (PET/CT) can provide this information. METHODS: An institutional review board-approved prospective intraindividual comparison trial on 35 patients who underwent fluorodeoxyglucose PET/CT and DWI-MRI within 6 weeks before and 6 weeks after Y90-RE to treat secondary-progressive liver metastases from solid cancers (20 colorectal, 13 breast, 2 other) was performed. An increase of minimal apparent diffusion coefficient (ADCmin) or decrease of maximum standard uptake value (SUVmax) by at least 30% was regarded as positive response. Long-term clinical and imaging follow-up was used to distinguish true- from false-response classifications. RESULTS: On the basis of long-term follow-up, 23 (66%) of 35 patients responded to the Y90 treatment. No significant changes of metastases size or contrast enhancement were observable on pretreatment versus posttreatment CT or magnetic resonance images.However, overall SUVmax decreased from 8.0 ± 3.9 to 5.5 ± 2.2 (P < 0.0001), and ADCmin increased from 0.53 ± 0.13 × 10(-3) mm2/s to 0.77 ± 0.26 × 10(-3) mm2/s (P < 0.0001). Pretherapeutic versus posttherapeutic changes of ADCmin and SUVmax correlated moderately (r = -0.53). In 4 of the 35 patients (11%), metastases were fluorodeoxyglucose-negative such that no response assessment was possible by PET. In 25 (71%) of the 35 patients, response classification by PET and DWI-MRI was concordant; in 6 (17%) of the 35, it was discordant. In 5 of the 6 patients with discordant classifications, follow-up confirmed diagnoses made by DWI. The positive predictive value to predict response was 22 (96%) of 23 for MRI and 15 (88%) of 17 for PET. The negative predictive value to predict absence was 11 (92%) of 12 for MRI and 10 (56%) of 18 for PET. Sensitivity for detecting response was significantly higher for MRI (96%; 22/23) than for PET (65%; 15/23) (P < 0.02). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging appears superior to PET/CT for early response assessment in patients with hepatic metastases of common solid tumors. It may be used in between lobar treatment sessions to guide further management of patients who undergo Y90-RE for hepatic metastases.

Liver dysplasia: US molecular imaging with targeted contrast agent enables early assessment.

PURPOSE: To investigate the ability of vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted ultrasonographic (US) microbubbles for the assessment of liver dysplasia in transgenic mice. MATERIALS AND METHODS: Animal experiments were approved by the governmental review committee. Nuclear factor-κB essential modulator knock-out mice with liver dysplasia and wild-type mice underwent liver imaging by using a clinical US system. Two types of contrast agents were investigated: nontargeted, commercially available, second-generation microbubbles (SonoVue) and clinically translatable PEGylated VEGFR2-targeted microbubbles (BR55). Microbubble kinetics was investigated over the course of 4 minutes. Targeted contrast material-enhanced US signal was quantified 5 minutes after injection. Competitive in vivo binding experiments with BR55 were performed in knock-out mice. Immunohistochemical and hematoxylin-eosin staining of liver sections was performed to validate the in vivo US results. Groups were compared by using the Mann-Whitney test. RESULTS: Peak enhancement after injection of SonoVue and BR55 did not differ in healthy and dysplastic livers (SonoVue, P = .46; BR55, P = .43). Accordingly, immunohistochemical findings revealed comparable vessel densities in both groups. The specificity of BR55 to VEGFR2 was proved by in vivo competition (P = .0262). While the SonoVue signal decreased similarly in healthy and dysplastic livers during the 4 minutes, there was an accumulation of BR55 in dysplastic livers compared with healthy ones. Furthermore, targeted contrast-enhanced US signal indicated a significantly higher site-specific binding of BR55 in dysplastic than healthy livers (P = .005). Quantitative immunohistologic findings confirmed significantly higher VEGFR2 levels in dysplastic livers (P = .02). CONCLUSION: BR55 enables the distinction of early stages of liver dysplasia from normal liver.

Assessment of inflammatory and fibrotic stenoses in patients with Crohn's disease using contrast-enhanced ultrasound and computerized algorithm: a pilot study.

PURPOSE: The development of stenosis is a typical complication of Crohn's disease and represents a serious diagnostic and therapeutic challenge. The aim of the present study was to define objective quantitative measures of stricture characteristics (fibrostenotic/cicartricial vs. inflammatory) using contrast-enhanced ultrasound (CEUS) in patients with stenotic Crohn's disease. MATERIALS AND METHODS: During a period of 18 months, 18 consecutive patients with Crohn's disease and manifestation of a localized significant small bowel stenosis were prospectively recruited. Standardized ultrasound (US) examination, color-coded duplex sonography and CEUS using SonoVue® were performed. Quantitative measurements of bowel wall vascularity were determined using computerized algorithms (Bracco QONTRAST software). The quality of stenosis (fibrostenotic vs. inflammatory) was classified in a 4-point scale, and the diagnostic/prognostic power of the US and clinical tests upon initial presentation were compared. RESULTS: We established a novel standardized CEUS procedure using computerized algorithms to quantitatively examine stenoses in Crohn's disease. An inflammatory origin of stenosis correlated significantly with a high Crohn's Disease Activity Index (CDAI) (p < 0.01), the length of stenosis (p < 0.01) as well as the Limberg score (p < 0.01). There was no correlation between the type of stenosis and quantitative results of CEUS. CONCLUSION: Although bowel wall vascularity can be quantitatively assessed in stenotic areas by CEUS, this analysis does not improve the diagnostic power for the objective determination of the quality of stenosis at a single measurement. Semiquantitative analysis of bowel wall vascularity, length of stenosis, and CDAI may help to discriminate the origin of small bowel stenosis in Crohn's disease.