FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel - results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO.

BACKGROUND: Ramucirumab and paclitaxel is the standard second-line therapy in patients with metastatic gastroesophageal adenocarcinoma. We report the efficacy and safety analyses of FOLFIRI and ramucirumab versus paclitaxel and ramucirumab after the failure of a platinum- and fluoropyrimidine-containing chemotherapy. METHODS: This multicenter, investigator initiated, phase II trial randomised patients with gastroesophageal adenocarcinoma to either FOLFIRI plus ramucirumab (RAM) (arm A) or paclitaxel plus RAM (arm B). The primary end-point was 6-month overall survival (OS) rate, with a proportion of ≥65% in arm A considered a positive signal for further investigation. RESULTS: 111 patients (65% of patients had prior docetaxel) were enrolled and 110 patients qualified for ITT population (arm A, 72; arm B, 38). The study did not meet the primary end-point for the comparison with historical control, as 6-month OS rate in the FOLFIRI plus RAM arm was 54% (95% CI 44-67). In between arm comparison, OS was similar (hazard ratio, HR 0.97 [95% CI 0.62-1.52]), while objective response rates (ORRs) and PFS were numerically better in arm A versus arm B (HR for PFS 0.73; ORR, 22% versus 11%). These differences were largely attributed to favourable efficacy results for arm A in docetaxel-pretreated patients (HR, 0.49; ORR, 25% versus 8%). In the safety population (n = 106), grade 3-5 adverse events were similar between arms (arm A, 75%; arm B, 68%). CONCLUSION: The RAMIRIS trial demonstrated feasibility of FOLFIRI plus RAM. While the study was formally negative, it provided a signal to further investigate this combination for the group of patients with previous docetaxel therapy. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03081143.

Plant diversity effects on forage quality, yield and revenues of semi-natural grasslands.

In agricultural settings, plant diversity is often associated with low biomass yield and forage quality, while biodiversity experiments typically find the opposite. We address this controversy by assessing, over 1 year, plant diversity effects on biomass yield, forage quality (i.e. nutritive values), quality-adjusted yield (biomass yield × forage quality), and revenues across different management intensities (extensive to intensive) on subplots of a large-scale grassland biodiversity experiment. Plant diversity substantially increased quality-adjusted yield and revenues. These findings hold for a wide range of management intensities, i.e., fertilization levels and cutting frequencies, in semi-natural grasslands. Plant diversity was an important production factor independent of management intensity, as it enhanced quality-adjusted yield and revenues similarly to increasing fertilization and cutting frequency. Consequently, maintaining and reestablishing plant diversity could be a way to sustainably manage temperate grasslands.

Independent Risk Factors for Fast-Track Failure Using a Predefined Fast-Track Protocol in Preselected Cardiac Surgery Patients.

OBJECTISVES: The purpose of this study was to identify the independent risk factors for fast-track failure (FTF) in cardiac surgery patients. DESIGN: A retrospective analysis. SETTING: A university-affiliated heart center. PARTICIPANTS: In a 2-year period, 1,704 consecutive preselected patients undergoing elective cardiac surgery were treated according to the local fast-track protocol in the postanesthetic care unit (PACU), bypassing the intensive care unit (ICU). MEASUREMENTS AND RESULTS: Independent risk factors for FTF in the univariate regression analysis were tested in a multivariate regression analysis. FTF was defined as any transfer of the preselected patient to the ICU. FTF was primary when the patient was transferred directly from the postanesthetic care unit to the ICU and secondary when the patient was transferred from the intermediate care unit or ward to the ICU. FTF rate was 11.6% for primary and 5.6% for secondary FTF. In the multivariate regression analysis, age>70 years, female sex, prolonged surgery, and prolonged cross-clamp time could be defined as independent risk factors for FTF. CONCLUSIONS: In a preselected patient population, fast-track treatment could be done with a low FTF rate. Independent risk factors for FTF are age, female sex, prolonged surgery, and prolonged cross-clamp time.

A specialized post anaesthetic care unit improves fast-track management in cardiac surgery: a prospective randomized trial.

INTRODUCTION: Fast-track treatment in cardiac surgery has become the global standard of care. We compared the efficacy and safety of a specialised post-anaesthetic care unit (PACU) to a conventional intensive care unit (ICU) in achieving defined fast-track end-points in adult patients after elective cardiac surgery. METHODS: In a prospective, single blinded, randomized study, 200 adult patients undergoing elective cardiac surgery (coronary artery bypass graft (CABG), valve surgery or combined CABG and valve surgery), were selected to receive their postoperative treatment either in the ICU (n = 100), or in the PACU (n = 100). Patients who, at the time of surgery, were in cardiogenic shock, required renal dialysis, or had an additive EuroSCORE of more than 10 were excluded from the study. The primary end points were: time to extubation (ET), and length of stay in the PACU or ICU (PACU/ICU LOS respectively). Secondary end points analysed were the incidences of: surgical re-exploration, development of haemothorax, new onset cardiac arrhythmia, low cardiac output syndrome, need for cardio-pulmonary resuscitation, stroke, acute renal failure, and death. RESULTS: Median time to extubation was 90 [50; 140] min in the PACU vs. 478 [305; 643] min in the ICU group (P < 0.001). Median length of stay in PACU was 3.3 [2.7; 4.0] hours vs. 17.9 [10.3; 24.9] hours in the ICU (P < 0.001). Of the adverse events examined, only the incidence of new onset cardiac arrhythmia (25 in PACU vs. 41 in ICU, P = 0.02) was statistically different between groups. CONCLUSIONS: Treatment in a specialised PACU rather than an ICU, after elective cardiac surgery leads to earlier extubation and quicker discharge to a step down unit, without compromising patient safety. TRIAL REGISTRATION: ISRCTN71768341. Registered 11 March 2014.

Recognition memory for high- and low-frequency words in adult normal and dyslexic readers: an event-related brain potential study.

Differences in word processing between adult developmental dyslexic (n = 12) and normal readers (n = 12) were studied using event-related brain potentials recorded while subjects performed a recognition memory task. During the first part of the experiment, words were presented consecutively, and within this phase one third of the words were repeated. Subjects had to indicate whether a given word had previously been seen or not. After a delay of 1 hr, a second phase was administered. Here, another list containing 33% old words (presented in Phase 1) and 66% new words was shown and an old/new decision was required. In both categories, half of the words presented in either phase were of high normative frequency, and the other half were of low-frequency in the German language. Recognition performance was superior in normal readers for both high- and low-frequency words. In Phase 1, a fronto-centrally distributed N400 repetition effect discriminated between correctly identified old and new words (new words more negative). This effect was present for dyslexic as well as normal readers and for high- and low-frequency words. Between 450 and 800 ms, a 'P600 old/new effect' emerged (ERPs evoked by old words were more positive than those for new words). This effect was larger for low-frequency words. In Phase 2, an old/new effect was obtained for normal readers only. These findings are discussed in relation to current concepts of dyslexia and of semantic processing.