Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

BACKGROUND: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcome of patients with liver cirrhosis. METHODS: In this retrospective international multicentric study, computed tomography (CT) scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. 1-year survival was primary and acute decompensation (oHE, variceal bleeding, ascites) secondary endpoint. RESULTS: 301 patients (169 male) were included in the training cohort. 30% of all patients presented >1 SPSS. TSA cut-off of 83 mm2 was determined to classify patients with small or large TSA (S-/L-TSA). L-TSA patients presented higher MELD (11 vs. 14) and more commonly history of oHE (12% vs. 21%, p83mm2 increases the risk for oHE and mortality in liver cirrhosis. Our results may have impact on clinical use of TSA/SPSS for risk stratification and clinical decision-making considering management of SPSS

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.Jonel Trebicka is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57, CRC1382), Cellex Foundation and European Union’s Horizon 2020 research and innovation program GALAXY study (No. 668031), LIVERHOPE (No. 731875) and MICROB-PREDICT (No. 825694) and the Cellex Foundation. Joan Genescà is a recipient of a Research Intensification grant from Instituto de Salud Carlos III, Spain. The study was partially funded by grants PI15/00066, and PI18/00947 from Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “Investing in your future”). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivasis supported by Instituto de Salud Carlos III. Macarena Simón-Talero is a recipient of the grant JR 17/00029 from Instituto de Salud Carlos II

How might acupuncture work? A systematic review of physiologic rationales from clinical trials

BACKGROUND: Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. METHODS: The author conducted a PubMed search to obtain a fair sample of acupuncture clinical trials published in English in 2005. Each article was reviewed for a physiologic rationale, as well as study objectives and outcomes, experimental and control interventions, country of origin, funding sources and journal type. RESULTS: Seventy-nine acupuncture clinical trials were identified. Twenty-six studies (33%) offered no physiologic rationale. Fifty-three studies (67%) posited a physiologic basis for acupuncture: 33 (62% of 53) proposed neurochemical mechanisms, 2 (4%) segmental nervous system effects, 6 (11%) autonomic nervous system regulation, 3 (6%) local effects, 5 (9%) effects on brain function and 5 (9%) other effects. No rationale was proposed for stroke; otherwise having a rationale was not associated with objective, positive or negative findings, means of intervention, country of origin, funding source or journal type. The dominant explanation for how acupuncture might work involves neurochemical responses and is not reported to be dependent on treatment objective, specific points, means or method of stimulation. CONCLUSION: Many acupuncture trials fail to offer a meaningful rationale, but proposing a rationale can help investigators to develop and test a causal hypothesis, choose an appropriate control and rule out placebo effects. Acupuncture may stimulate self-regulatory processes independent of the treatment objective, points, means or methods used; this would account for acupuncture's reported benefits in so many disparate pathologic conditions

Insights into CODE-DE - Germany's Copernicus Data and Exploitation Platform

This article presents and analyses the modular architecture and capabilities of CODE-DE (Copernicus Data and Exploitation Platform - Deutschland, www.code-de.org), the integrated German operational environment for accessing and processing Copernicus data and products, as well as the methodology to establish and operate the system. Since March 2017, CODE-DE has been online with access to Sentinel-1 and Sentinel-2 data, to Sentinel-3 data shortly after this time, and since March 2019 with access to Sentinel-5P data. These products are available and accessed by 1,682 registered users as of March 2019. During this period 654,895 products were downloaded and a global catalogue was continuously updated, featuring a data volume of 814 TByte based on a rolling archive concept supported by a reload mechanism from a long-term archive. Since November 2017, the element for big data processing has been operational, where registered users can process and analyse data themselves specifically assisted by methods for value-added product generation. Utilizing 195,467 core and 696,406 memory hours, 982,948 products of different applications were fully automatically generated in the cloud environment and made available as of March 2019. Special features include an improved visualization of available Sentinel-2 products, which are presented within the catalogue client at full 10 m resolution

Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis.

Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography. This study evaluated fat-free muscle area (FFMA) as a marker of sarcopenia using magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training cohort of 71 patients compared computed tomography-measured transversal psoas muscle thickness with FFMA. In 15 patients MRI was performed before and after TIPS, and in 12 patients follistatin serum measurements were carried out. The results on FFMA were confirmed in a validation cohort of 45 patients. FFMA correlated with follistatin and transversal psoas muscle thickness and showed slightly better association with survival than transversal psoas muscle thickness. Gender-specific cutoff values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure. FFMA was an independent predictor of survival in these patients. This study offers an easy-to-apply MRI-based measurement of fat-free muscle mass as a marker of sarcopenia in decompensated patients; while TIPS might improve sarcopenia and thereby survival, persistence of sarcopenia after TIPS is associated with a reduced response to TIPS and a higher risk of acute-on-chronic liver failure development and mortality. (Hepatology 2018;67:1014-1026)

Characterization of Severe Arterial Phase Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI – Assessment of Interrater Agreement and Reliability

Purpose To assess the interrater agreement and reliability of experienced abdominal radiologists in the characterization and grading of arterial phase gadoxetate disodium-related respiratory motion artifact on liver MRI. Materials and Methods This prospective multicenter study was initiated by the working group for abdominal imaging within the German Roentgen Society (DRG), and approved by the local IRB of each participating center. 11 board-certified radiologists independently reviewed 40 gadoxetate disodium-enhanced liver MRI datasets. Motion artifacts in the arterial phase were assessed on a 5-point scale. Interrater agreement and reliability were calculated using the intraclass correlation coefficient (ICC) and Kendall coefficient of concordance (W), with p<0.05 deemed significant. Results The ICC for interrater agreement and reliability were 0.983 (CI 0.973-0.990) and 0.985 (CI 0.978-0.991), respectively (both p<0.0001), indicating excellent agreement and reliability. Kendall's W for interrater agreement was 0.865. A severe motion artifact, defined as a mean motion score 4 in the arterial phase was observed in 12 patients. In these specific cases, a motion score 4 was assigned by all readers in 75% (n=9/12 cases). Conclusion Differentiation and grading of arterial phase respiratory motion artifact is possible with a high level of inter-/intrarater agreement and interrater reliability, which is crucial for assessing the incidence of this phenomenon in larger multicenter studies. Key Points Inter- and intrarater agreement for motion artifact scoring is excellent among experienced readers. Interrater reliability for motion artifact scoring is excellent among experienced readers. Characterization of severe motion artifacts proved feasible in this multicenter study. Citation Format Ringe KI, Luetkens JA, Fimmers R etal. Characterization ofSevere Arterial Phase Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI - Assessment of Interrater Agreement and Reliability. Fortschr Rontgenstr 2017; 190: 341-347 Zusammenfassung Ziel Evaluation der Interreader-ubereinstimmung und -Reliabilitat zwischen erfahrenen Radiologen im Hinblick auf die Beurteilung und Graduierung atemabhangiger Artefakte in der Leber-MRT mit Gd-EOB-DTPA. Material und Methoden In dieser prospektiven Multizenterstudie (initiiert durch die AG Gastrointestinal- und Abdominaldiagnostik der DRG) wurden Gd-EOB-DTPA verstarkte MRT-Untersuchungen von 40 Patienten (25 Manner, 15 Frauen; mittleres Alter 59 Jahre) durch 11 erfahrene Radiologen/innen aus Deutschland und der Schweiz ausgewertet. Evaluiert wurden das Auftreten und der Schweregrad atemabhangiger Artefakte in der arteriellen Phase der KM-Dynamik anhand eines 5-Punkte Scores. Zur Beurteilung von ubereinstimmung und Reliabilitat des Scorings zwischen den Radiologen wurden der Intraklassen-Korrelationskoeffizient (ICC) und der Kendall Konkordanzkoeffizient (W) berechnet. Ergebnisse Die ubereinstimmung zwischen den Radiologen bezuglich der Graduierung des Schweregrads des Artefakts war mit einem ICC von 0,933 (95% Konfidenzintervall 0,973-0,990; p<0,0001) bzw. einem Kendall W von 0,865 sehr gut. Die Reliabilitat bzgl. der Unterscheidung verschiedener Schweregrade war zwischen den Radiologen ebenfalls sehr gut mit einem ICC von 0,985 (95% Konfidenzintervall 0,978-0,991; p<0,0001). Schwere atemabhangige Artefakte (definiert als ein Score 4) wurden in 12 Untersuchungen beobachtet. In diesen Fallen wurde in 75% (9/12) von allen Radiologen ein Score 4 vergeben. Schlussfolgerung Die Differenzierung und Charakterisierung atemabhangiger Artefakte in der arteriellen Phase der MRT mit Gd-EOB-DTPA durch verschiedene Radiologen ist mit hoher ubereinstimmung und Reliabilitat moglich. Die zuverlassige und ubereinstimmende Bewertung von Artefakten durch unterschiedliche Radiologen ist eine unabdingbare Voraussetzung fur die Durchfuhrung gro ss er Multizenterstudien. Die Ergebnisse dieser Arbeit schaffen hierfur die Grundlage. Kernaussagen: Die Inter- und Intraraterubereinstimmung fur die Beurteilung atemabhangiger Artefakte ist sehr gut. Die Interrater Reliabilitat unter erfahrenen Radiologen bezuglich der Graduierung von atemabhangigen Artefakten ist sehr gut. Die Charakterisierung schwerer atemabhangiger Artefakte erwies sich in dieser Multizenterstudie als zuversichtlich moglich

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis.

BACKGROUND & AIMS Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. METHODS In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. RESULTS A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. CONCLUSION This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. LAY SUMMARY The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS