Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients

The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage

Influence of denitrifiers abundance on N2O emissions in long term tillage system under a rainfed legume crop

Current studies about nitrous oxide (N2O) emissions from legume crops have raised considerable doubt, observing a high variability between sites (0.03-7.09 kg N2O–N ha−1 y -1) [1]. This high variability has been associated to climate and soil conditions, legume species and soil management practices (e.g. conservation or conventional tillage). Conservation tillage (i.e. no tillage (NT) and minimum tillage (MT)) has spread during the last decades because promotes several positive effects (increase of soil organic content, reduction of soil erosion and enhancement of carbon (C) sequestration). However, these benefits could be partly counterbalanced by negative effects on the release of N2O emissions. Among processes responsible for N2O production and consumption in soils, denitrification plays an importantrole both in tilled and no-tilled ropping systems [2]. Recently, amplification of functional bacterial genes involved in denitrification is being used to examine denitrifiers abundance and evaluate their influence on N2O emissions. NirK and nirS are functional genes encoding the cytochrome cd1 and copper nitrite reductase, which is the key enzyme regulating the denitrification process

In Vitro Antioxidant and Antihypertensive Activity of Edible Insects Flours (Mealworm and Grasshopper) Fermented with Lactococcus lactis Strains

The objective of the present study was to evaluate the potential antioxidant and angiotensin converting enzyme inhibition (ACEI) activity of edible insect flours fermented with Lactococcus lactis strains. For the fermentation, mealworm and grasshoppers flours were dissolved (0.5% w/v) in buffer solution (pH 7.0) and individually inoculated (3%) with Lactococcus lactis strains (NRRL B-50571, NRRL B-50572). The samples were incubated for 72 h at 30 ◦C, and the pH was recorded. The degree of hydrolysis (DH) and protein content were determined. The total polyphenol compounds, antioxidant activity (ABTS, DPPH, ORAC, and FRAP), and ACEI of the \u3c3 kDa fractions were ana- lyzed. The pH of the fermented samples decreased to 3.5–3.9 (p \u3c 0.05). The fermented grasshopper flour showed an increased DH (0.42%) and overall higher total polyphenol content (8.23 mg Gallic Acid Equivalent/mL). In general, the highest antioxidant activity was for the grasshopper fractions fermented for 24 h by Lactococcus lactis NRRL B-50572, which also showed 23.47% ACEI inhibition with an IC50 of 0.97 mg/mL. The peptide profile obtained increased after fermentation, being higher for the mealworm flour fermented sample. This study presents, for the first time, the use of specific strains of Lactococus lactis for fermenting edible insect-derived products in the production of bioactive compounds with potential antioxidant and antihypertensive activity

Optimal Loop-Unrolling Mechanisms and Architectural Extensions for an Energy-Efficient Design of Shared Register Files in MPSoCs

In this paper we introduce a new hardware/software approach to reduce the energy of the shared register file in upcoming embedded architectures with several VLIW processors. This work includes a set of architectural extensions and special loop unrolling techniques for the compilers of MPSoC platforms. This complete hardware/software support enables reducing the energy consumed in the register file of MPSoC architectures up to a 60% without introducing performance penalties

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation

This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035)

XIAP as a Target of New Small Organic Natural Molecules Inducing Human Cancer Cell Death

X-linked inhibitor of apoptosis protein (XIAP) is an emerging crucial therapeutic target in cancer. We report on the discovery and characterisation of small organic molecules from Piper genus plants exhibiting XIAP antagonism, namely erioquinol, a quinol substituted in the 4-position with an alkenyl group and the alkenylphenols eriopodols A-C. Another isolated compound was originally identified as gibbilimbol B. Erioquinol was the most potent inhibitor of human cancer cell viability when compared with gibbilimbol B and eriopodol A was listed as intermediate. Gibbilimbol B and eriopodol A induced apoptosis through mitochondrial permeabilisation and caspase activation while erioquinol acted on cell fate via caspase-independent/non-apoptotic mechanisms, likely involving mitochondrial dysfunctions and aberrant generation of reactive oxygen species. In silico modelling and molecular approaches suggested that all molecules inhibit XIAP by binding to XIAP-baculoviral IAP repeat domain. This demonstrates a novel aspect of XIAP as a key determinant of tumour control, at the molecular crossroad of caspase-dependent/independent cell death pathway and indicates molecular aspects to develop tumour-effective XIAP antagonists

Involvement of patients or their representatives in quality management functions in EU hospitals:implementation and impact on patient-centred care strategies

OBJECTIVE: The objective of this study was to describe the involvement of patients or their representatives in quality management (QM) functions and to assess associations between levels of involvement and the implementation of patient-centred care strategies. DESIGN: A cross-sectional, multilevel STUDY DESIGN: that surveyed quality managers and department heads and data from an organizational audit. SETTING: Randomly selected hospitals (n = 74) from seven European countries (The Czech Republic, France, Germany, Poland, Portugal, Spain and Turkey). PARTICIPANTS: Hospital quality managers (n = 74) and heads of clinical departments (n = 262) in charge of four patient pathways (acute myocardial infarction, stroke, hip fracture and deliveries) participated in the data collection between May 2011 and February 2012. MAIN OUTCOME MEASURES: Four items reflecting essential patient-centred care strategies based on an on-site hospital visit: (1) formal survey seeking views of patients and carers, (2) written policies on patients' rights, (3) patient information literature including guidelines and (4) fact sheets for post-discharge care. The main predictors were patient involvement in QM at the (i) hospital level and (ii) pathway level. RESULTS: Current levels of involving patients and their representatives in QM functions in European hospitals are low at hospital level (mean score 1.6 on a scale of 0 to 5, SD 0.7), but even lower at departmental level (mean 0.6, SD 0.7). We did not detect associations between levels of involving patients and their representatives in QM functions and the implementation of patient-centred care strategies; however, the smallest hospitals were more likely to have implemented patient-centred care strategies. CONCLUSIONS: There is insufficient evidence that involving patients and their representatives in QM leads to establishing or implementing strategies and procedures that facilitate patient-centred care; however, lack of evidence should not be interpreted as evidence of no effect

EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting

[EN] Introduction: Durvalumab is the new standard of care for unresectable locally advanced NSCLC, with PD-L1 _1% and who did not have progression after CRT treatment in the European Union. Our study compares the effectiveness and the frequency of radiation pneumonitis in patients treated with concurrent CRT with or without durvalumab consolidation during the same period in real clinical practice. Methods: A single-center retrospective study. 71 treated patients with unresectable stage III NSCLC were included between March 2018 and December 2021, 37 with CRT followed by durvalumab and 34 with CRT alone. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated since the date of the end CRT. Propensity score matching (PSM) 1:1 was used to account for differences in baseline characteristics. Results: Median age was 67 years (range 46-82). 25.4% of the patients were _75 years old. 78.9% were men and 53.5% former smokers. 54.9% had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel (43.7%), receiving induction chemotherapy in up to 54.9% of patients. 73.2% received between 60-66 Gy doses of radiotherapy. Median time from end of CRT to onset durvalumab was 44 days (range 13-120) with a median of 14 infusions (range 6-27). Of the 34 patients without durvalumab treatment, the expression PD-L1 <1% (58.8%) was the most frequent cause for rejecting consolidation therapy. After PSM analysis, patients distributions were well balanced. With a median follow-up of 19.7 months (range 1.4-36.6); median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013). Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab and 29.9 months (95% CI, 23.3-36.6) with durvalumab (p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and 49% vs 100%, 86% and 74%, respectively. The rate of radiation pneumonitis was more frequent with durvalumab consolidation (56.8% against 44.1%), (p¼0.346), especially within 3 months after CRT. G3 pneumonitis was only observed in the consolidation therapy. Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation after CRT in real-world patients with unresectable stage III NSCLC. Further sample and longer follow-up are required to obtain more accurate results. Active surveillance and appropriate management for radiation pneumonitis are needed, in especially in candidates for consolidation treatmentS

EP05.02-002 Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?

[EN] Introduction: Durvalumab received EMA approval as consolidation therapy (CT) for unresectable stage III NSCLC with PD-L1 _1% and who did not have progression after CRT. Our objective was to analyze in real clinical practice the effectiveness of durvalumab and explore the clinical factors that may be associated with the benefit from CT. Methods: Retrospective study was made at Hospital of Leon (Spain), including 37 patients with locally advanced NSCLC treated with durvalumab after CRT treatment between March 2018 and october 2021 (40.5% patients were included in the durvalumab early access program). The neutrophil-to-lymphocyte ratio (NLR) could identified after CRT as a factor that may be benefit from durvalumab. Results: Median age was 67 years (range 46-82 years). 40.5% of patients were _70 years old. 78.4% were male and 51.4% smokers. 54% had non-squamous histology. PD-L1 expression was <1% in 5% and not available in 8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were 24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to onset durvalumab was 44 days (range 13-120 days). Overall median CT duration was 214.8 days (range 69-399 days) with a median of 14 infusions (range 6-27 infusions). With a median follow up of 19.7 months (range 1.4-34.9 months); 67.6% had stopped CT: 37.8% due to completing treatment, 16.2% disease progression, 10.8% adverse event and 2.7% due to COVID19 infection. Median real-world progressionfree survival (rwPFS) was 17 months (95% CI, 11-23). Median realworld overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). % rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively. For patients with post-CRT NLR not exceeding the cohort median value of 6, receipt of durvalumab was associated with an improvement in rwOS (median not reached vs 25.7 months; p¼0.025). 56.8% patients had any grade of radiation pneumonitis (median time from CRT start: 119 days [range 36-241 days]). Of these, 19% patients developed worsening of radiation pneumonitis with durvalumab. 54,1% developed immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation in this patients population in a real-life setting. We identified low NLR after CRT as a potentially predictive factor for the benefit of CT in locally advanced NSCLC.S