Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib.

BACKGROUND: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. METHODS: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. RESULTS: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. CONCLUSION: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC

Correlation of liver enhancement in gadoxetic acid-enhanced MRI with liver functions: a multicenter-multivendor analysis of hepatocellular carcinoma patients from SORAMIC trial

OBJECTIVES To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. METHODS A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin ALBI), and scanner characteristics were analyzed using uni- and multivariate analyses. RESULTS There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). CONCLUSIONS The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. KEY POINTS • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors

How to measure behavioural spillovers: a methodological review and checklist

A growing stream of literature at the interface between economics and psychology is currently investigating ‘behavioural spillovers’ in (and across) different domains, including health, environmental, and pro-social behaviours. A variety of empirical methods have been used to measure behavioural spillovers to date, from qualitative self-reports to statistical/econometric analyses, from online and lab experiments to field experiments. The aim of this paper is to critically review the main experimental and non-experimental methods to measure behavioural spillovers to date, and to discuss their methodological strengths and weaknesses. A consensus mixed-method approach is then discussed which uses between-subjects randomisation and behavioural observations together with qualitative self-reports in a longitudinal design in order to follow up subjects over time. In particular, participants to an experiment are randomly assigned to a treatment group where a behavioural intervention takes place to target behaviour 1, or to a control group where behaviour 1 takes place absent any behavioural intervention. A behavioural spillover is empirically identified as the effect of the behavioural intervention in the treatment group on a subsequent, not targeted, behaviour 2, compared to the corresponding change in behaviour 2 in the control group. Unexpected spillovers and additional insights (e.g., drivers, barriers, mechanisms) are elicited through analysis of qualitative data. In the spirit of the pre-analysis plan, a systematic checklist is finally proposed to guide researchers and policy- makers through the main stages and features of the study design in order to rigorously test and identify behavioural spillovers, and to favour transparency, replicability, and meta-analysis of studies

Einfluss von Rituximab auf die akute Graft-versus-Host-Reaktion nach allogener Stammzelltransplantation

B-Lymphozyten sind bei der Vermittlung chronischer T-zellulärer Auto- und Alloimmunreaktionen, wie zum Beispiel bei der Multiplen Sklerose, an zentraler Stelle beteiligt. In den letzten Jahren hat sich Rituximab unter anderem als effektive Therapie der steroidrefraktären chronischen GvH bewährt. Die Studie untersucht den Einfluss von Rituximab auf die akute GvH. Des Weiteren werden Daten zur Generierung von Hypothesen über mögliche Pathomechanismen vorgestellt. Es wurden 34 Patienten in die Studie eingeschlossen. 17 Patienten erhielten Rituximab in ihrer Konditionierung. Nur bei drei dieser Patienten ist aGvH aufgetreten (17.6%). Ohne Rituximab lag die aGvH-Rate bei 82.3% (14/17; p < 0,01). Berücksichtigt man lediglich aGvH II-IV° ergab sich eine Rate von 52,9% (9/17; p = 0,03). Wenn Patienten Rituximab und ATG in der Konditionierung zusammen erhielten (n = 10), war die aGvH-Rate sogar bei 0% (0/10). In der Vergleichsgruppe „ATG ohne Rituximab“ (n = 17) waren es zehn aGvH-Fälle (58.8%; p < 0,01) bzw. fünf mit aGvH II-IV° (29,4%; p < 0,01). Das Odds Ratio für aGvH nach Rituximabtherapie lag bei 0,043, während es im direkten Vergleich für ATG bei 0,94 lag. Patienten mit Rituximab hatten weniger Monocyten und B-Lymphozyten nach der Transplantation. Die CD8+ T-Zell-Rekonstitution war beschleunigt. Die Leukozytenbildung war ebenfalls verbessert bei gleichzeitig verringerten Thrombozytenzahlen in der Rituximabgruppe. Zusammenfassend zeigt diese Studie den deutlichen Effekt von Rituximab auf die aGvH-Inzidenz und lässt neue Schlüsse auf die mögliche Pathogenese zu.von Vincent Manuel Schütt

In situ XPS analysis of the electronic structure of silicon and titanium thin films exposed to low-pressure inductively-coupled RF plasma

Carbon contamination of synchrotron and free-electron lasers beamline optics continues to be a major nuisance due to the interaction of the intense photon beams with the surfaces of the optical elements in the presence of residual gases even in ultrahigh vacuum (UHV) conditions. Among the available in situ cleaning strategies, low-pressure radio frequency (RF) plasma treatment has emerged as a useful and relatively simple approach to remove such carbon contamination. However, the irreversible damage that the plasma may induce in such critical surfaces has to be carefully characterized before its general application. In this study, we focus on reducing the amount of carbon from UHV chamber inside surfaces via silicon and titanium coatings using a low-pressure inductively-coupled downstream plasma source and we characterize the surface alterations by in situ X-ray photoemission spectroscopy (XPS). The in situ mirror cleaning is simulated by means of silicon wafers. We observe upward band bending, which translates into lower binding energies of the photoemission lines, that we attribute to the generation of vacancies and trapped charges in the oxide layers

In situ XPS analysis of the electronic structure of silicon and titanium thin films exposed to low-pressure inductively-coupled RF plasma

Carbon contamination of synchrotron and free-electron lasers beamline optics continues to be a major nuisance due to the interaction of the intense photon beams with the surfaces of the optical elements in the presence of residual gases even in ultrahigh vacuum (UHV) conditions. Among the available in situ cleaning strategies, low-pressure radio frequency (RF) plasma treatment has emerged as a useful and relatively simple approach to remove such carbon contamination. However, the irreversible damage that the plasma may induce in such critical surfaces has to be carefully characterized before its general application. In this study, we focus on reducing the amount of carbon from UHV chamber inside surfaces via silicon and titanium coatings using a low-pressure inductively-coupled downstream plasma source and we characterize the surface alterations by in situ X-ray photoemission spectroscopy (XPS). The in situ mirror cleaning is simulated by means of silicon wafers. We observe upward band bending, which translates into lower binding energies of the photoemission lines, that we attribute to the generation of vacancies and trapped charges in the oxide layers.This research was supported by the Government of Catalonia’s Industrial Doctorates Plan and by the Spanish Ministry of Economy and Competitiveness (MINECO) under Contract No. PGC2018-095032-B-100. The ICN2 is funded by the CERCA program/Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa program of MINECO (Grant SEV-2017-0706).Peer reviewe

Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability

Purpose!#!Magnetic resonance imaging (MRI) signal intensity is correlated to structural postoperative changes of the anterior cruciate ligament (ACL) autograft. The purpose of this study was to investigate the ACL autograft maturation process via MRI over 2 years postoperatively, compare it to a native ACL signal and correlate the results with clinical outcome, return to preinjury sports levels, and knee laxity measurements.!##!Methods!#!ACL autograft signal intensity was measured in 17 male patients (age, 28.3 ± 7.0 years) who underwent ACL reconstruction with hamstring autograft at 6 weeks, 3-, 6-, 12-, and 24 months postoperatively by 3 Tesla MRI. Controls with an intact ACL served as control group (22 males, 8 females; age, 26.7 ± 6.8 years). An ACL/PCL ratio (APR) and ACL/muscle ratio (AMR) was calculated to normalize signals to soft tissue signal. APR and AMR were compared across time and to native ACL signal. Clinical outcome scores (IKDC, Lysholm), return to preinjury sports levels (Tegner activity scale), and knee laxity measurement (KT-1000) were obtained and correlated to APR and AMR at the respective time points.!##!Results!#!The APR and AMR of the ACL graft changed significantly from the lowest values at 6 weeks to reach the highest intensity after 6 months (p &amp;lt; 0.001). Then, the APR and AMR were significantly different from a native ACL 6 months after surgery (p &amp;lt; 0.01) but approached the APR and AMR of the native ACL at 1- and 2 years after surgery (p &amp;lt; 0.05). The APR changed significantly during the first 2 years postoperatively in the proximal (p &amp;lt; 0.001), mid-substance (p &amp;lt; 0.001), and distal (p &amp;lt; 0.01) intraarticular portion of the ACL autograft. A hypo-intense ACL MRI signal was associated with return to the preinjury sports level (p &amp;lt; 0.05). No correlation was found between ACL MRI graft signal and clinical outcome scores or KT-1000 measurements.!##!Conclusion!#!ACL grafts undergo a continuous maturation process in the first 2 years after surgery. The ACL graft signals became hyper-intense 6 months postoperatively and approximated the signal of a native intact ACL at 12- and 24 months. Patients with a hypo-intense ACL graft signal at 2 years follow-up were more likely to return to preinjury sports levels. The results of the present study provide a template for monitoring the normal ACL maturation process via MRI in case of prolonged clinical symptoms. However, subjective outcome and clinical examination of knee laxity remain important to assess the treatment success and to allow to return to sports.!##!Level of evidence!#!III

Subsurface Fine-Scale Patterns in an Anticyclonic Eddy Off Cap-Vert Peninsula Observed From Glider Measurements

International audienceGlider measurements acquired along four transects between Cap-Vert Peninsula and the Cape Verde archipelago in the eastern tropical North Atlantic during March-April 2014 were used to investigate fine-scale stirring in an anticyclonic eddy. The anticyclone was formed near 12°N off the continental shelf and propagated northwest toward the Cape Verde islands. At depth, between 100 and -400 m, the isolated anticyclone core contained relatively oxygenated, low-salinity South Atlantic Central Water, while the surrounding water masses were saltier and poorly oxygenated. The dynamical and thermohaline subsurface environment favored the generation of fine-scale horizontal and vertical temperature and salinity structures in and around the core of the anticyclone. These features exhibited horizontal scales of O(10-30 km) relatively small with respect to the eddy radius of O(150 km). The vertical scales of O(5-100 m) were associated to density-compensated gradient. Spectra of salinity and oxygen along isopycnals revealed a slope of around k-2 in the 10- to 100-km horizontal scale range. Further analyses suggest that the fine-scale structures are likely related to tracer stirring processes. Such mesoscale anticyclonic eddies and the embedded fine-scale tracers in and around them could play a major role in the transport of South Atlantic Central Water masses and ventilation of the North Atlantic Oxygen Minimum Zone

Extrahepatic Disease in Hepatocellular Carcinoma: Do We Always Need Whole-Body CT or Is Liver MRI Sufficient? A Subanalysis of the SORAMIC Trial

Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC