66 research outputs found
Lack of sex-related analysis and reporting in Cochrane Reviews : a cross-sectional study
Background: Sex-specific analysis and reporting may allow a better understanding of intervention effects and can support the decision-making process. Well-conducted systematic reviews (SRs), like those carried out by the Cochrane Collaboration, provide clinical responses transparently and stress gaps of knowledge. This study aimed to describe the extent to which sex is analysed and reported in a cross-section of Cochrane SRs of interventions, and assess the association with the gender of main authorships. Methods: We searched SRs published during 2018 within the Cochrane Database of Systematic Reviews. An investigator appraised the sex-related analysis and reporting across sections of SRs and collected data on gender and country of affiliation of the review first and last authors, and a second checked for accuracy. We conducted descriptive statistics and bivariate logistic regression to explore the association between the gender of the authors and sex-related analysis and reporting. Results: Six hundred and ten Cochrane SRs were identified. After removing those that met no eligibility criteria, 516 reviews of interventions were included. Fifty-six reviews included sex-related reporting in the abstract, 90 considered sex in their design, 380 provided sex-disaggregated descriptive data, 142 reported main outcomes or performed subgroup analyses by sex, and 76 discussed the potential impact of sex or the lack of such on the interpretations of findings. Women represented 53.1 and 42.2% of first and last authorships, respectively. Women authors (in first and last position) had a higher possibility to report sex in at least one of the review sections (OR 2.05; CI 95% 1.12-3.75, P=0.020) than having none. Conclusions: Sex consideration amongst Cochrane SRs was frequently missing. Structured guidance to sex-related analysis and reporting is needed to enhance the external validity of findings. Likewise, including gender diversity within the research workforce and relevant authorship positions may foster equity in the evidence generated
Capturing yeast associated with grapes and spontaneous fermentations of the Negro Saurí minority variety from an experimental vineyard near León
‘Microbial terroir’ relates to the infuence of autochthonous yeasts associated with a grape cultivar on the resultant wine. Geographic region, vineyard site and topography, climate and vintage infuence the biodiversity of these microbial communities. Current research focus attempts to correlate their ‘microbial fngerprint’ to the sensorial and chemical characteristics of varietal wines from distinct geographical wine regions. This study focuses on the minor red grape variety, Negro Saurí, which has seen a resurgence in the León Appellation of Origin in Spain as a varietal wine. An experimental vineyard at Melgarajo S.A. (42° 15′ 48.68_N 5° 9′ 56.66_W) was sampled over four consecutive vintages, with autochthonous yeasts being isolated from grapes, must and pilot-scale un-inoculated fermentations, and identifed by ITS sequencing. Forty-nine isolates belonging to Metschnikowia pulcherrima, Lachancea thermotolerans, Hanseniaspora uvarum and Torulaspora delbrueckii were isolated from grapes and must, and early stages of fermentation dependent on seasonal variation. Saccharomyces cerevisiae predominated throughout fermentation, as a heterogeneous and dynamic population, with seven major biotypes identifed amongst 110 isolates across four consecutive vintages. Twenty-four S. cerevisiae isolates representing fve strains dominated in two or more vintages. Their persistence through fermentation warrants further validation of their oenological properties as starter culturesIsora González‑Alonso, Michelle Elisabeth Walker, María‑Eva Vallejo‑Pascual,
Gérmán Naharro‑Carrasco and Vladimir Jirane
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
Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis : Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model
Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P <.001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P <.001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF
Metabolic engineering to simultaneously activate anthocyanin and proanthocyanidin biosynthetic pathways in Nicotiana spp
[EN] Proanthocyanidins (PAs), or condensed tannins, are powerful antioxidants that remove harmful free oxygen radicals from cells. To engineer the anthocyanin and proanthocyanidin biosynthetic pathways to de novo produce PAs in two Nicotiana species, we incorporated four transgenes to the plant chassis. We opted to perform a simultaneous transformation of the genes linked in a multigenic construct rather than classical breeding or retransformation approaches. We generated a GoldenBraid 2.0 multigenic construct containing two Antirrhinum majus transcription factors (AmRosea1 and AmDelila) to upregulate the anthocyanin pathway in combination with two Medicago truncatula genes (MtLAR and MtANR) to produce the enzymes that will derivate the biosynthetic pathway to PAs production. Transient and stable transformation of Nicotiana benthamiana and Nicotiana tabacum with the multigenic construct were respectively performed. Transient expression experiments in N. benthamiana showed the activation of the anthocyanin pathway producing a purple color in the agroinfiltrated leaves and also the effective production of 208.5 nmol (-) catechin/g FW and 228.5 nmol (-) epicatechin/g FW measured by the p-dimethylaminocinnamaldehyde (DMACA) method. The integration capacity of the four transgenes, their respective expression levels and their heritability in the second generation were analyzed in stably transformed N. tabacum plants. DMACA and phoroglucinolysis/HPLC-MS analyses corroborated the activation of both pathways and the effective production of PAs in T0 and T1 transgenic tobacco plants up to a maximum of 3.48 mg/g DW. The possible biotechnological applications of the GB2.0 multigenic approach in forage legumes to produce "bloatsafe" plants and to improve the efficiency of conversion of plant protein into animal protein (ruminal protein bypass) are discussed.This work was supported by grants BIO2012-39849-C02-01 and BIO2016-75485-R from the Spanish Ministry of Economy and Competitiveness (MINECO) (http://www.idi.mineco.gob.es/portal/site/MICINN) to LAC and a fellowship of the JAE-CSIC program to SF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Fresquet-Corrales, S.; Roque Mesa, EM.; Sarrión-Perdigones, A.; Rochina, M.; López-Gresa, MP.; Díaz-Mula, HM.; Belles Albert, JM.... (2017). Metabolic engineering to simultaneously activate anthocyanin and proanthocyanidin biosynthetic pathways in Nicotiana spp. PLoS ONE. 12(9). https://doi.org/10.1371/journal.pone.0184839Se018483912
International lower limb collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures
Trauma remains a major cause of mortality and disability across the world1, with a higher burden in developing nations2. Open lower extremity injuries are devastating events from a physical3, mental health4, and socioeconomic5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability6. This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries
Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project
Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons.
Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II.
Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers.
Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry
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