Cancer surgery induces inflammation, immunosuppression and neo-angiogenesis, but is it influenced by analgesics?

Grant information: This work was exclusively supported by the Department of Anesthesiology of the Université catholique de Louvain, St-Luc Hospital, Belgium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Diagnosis of alpha-1 antitrypsin deficiency : a population-based study

Altres ajuts: This study was funded by unrestricted grants from Grifols, Fundació Catalana de Pneumologia, and the Spanish Society of Pneumology and Thoracic Surgery.Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain. We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested. A total of 12,409 AAT determinations were performed (5,559 in 2007-2008 and 6,850 in 2010-2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50-100 mg/dL), 24 (0.2%) individuals had a severe deficiency (<50 mg/dL), with a prevalence of 0.19 cases of severe deficiency per 100 determinations. Nine (41%) of the adults with severe deficiency had a previous diagnosis of COPD/emphysema, and four (16.7%) were diagnosed with COPD within 6 months. The number of AAT determinations in the PC is low in relation to the prevalence of COPD but increased slightly along the study period. The indication to perform the test is not always clear, and patients detected with deficiency are not always referred to a specialist

Categories of Resistance, Antibiosis and Tolerance, to Biotype I Greenbug (\u3ci\u3eSchizaphis graminum\u3c/i\u3e (Rondani) Homoptera: Aphididae) in Four Sorghum (\u3ci\u3eSorghum bicolor\u3c/i\u3e (L.) Moench. Poales:Gramineae) Hybrids

Resistance categories (antibiosis and tolerance) of four sorghum (Sorghum bicolor (L.) Moench) hybrids to biotype I greenbug, Schizaphis graminum (Rondani), were determined in environmental growth chamber and field studies. Greenbug weight and fecundity were lower on ‘Cargill 607E’ compared with ‘Cargill 797’. Percentage of leaf damage area was significantly less on two resistant hybrids (Cargill 607E and Cargill 797) after a 14-d greenbug feeding period compared to two susceptible hybrids (‘Golden Harvest 510B’ and Garst 5715). In growth chamber studies on sorghum seedlings, ‘Cargill 607E’ and ‘Cargill 797’ reduced greenbug weight significantly compared with ‘Golden Harvest 510B’ and ‘Garst 5715’. Greenbug weight was 2.9 mg/25 greenbugs on ‘Cargill 607E’, 3.1 mg/25 greenbugs on ‘Cargill 797’, 3.9 mg/25 greenbugs on ‘Golden Harvest 510B’, and 4.8 mg/25 greenbugs on ‘Garst 5715’. On field grown sorghum plants, ‘Cargill 797’ did not reduce greenbug growth compared with ‘Golden Harvest 510B’. ‘Cargill 607E’ had a negative impact on weight of greenbugs. Greenbug weight was 7.9 mg/25 greenbugs on ‘Cargill 607E’, 9.2 mg/25 greenbugs on ‘Cargill 797’, and 10.0 mg/25 greenbugs on ‘Golden Harvest 510B’. ‘Cargill 607E’ and ‘Cargill 797’ were resistant to biotype I greenbugs compared with susceptible ‘Golden Harvest 510B’ and ‘Garst 5715’. Antibiosis was confirmed as the primary category of resistance in ‘Cargill 607E.’ ‘Cargill 797’ was primarily tolerant but may have some level of antibiosis, because smaller greenbugs developed in some of the studies

Diversity As A Key To Analyze French Organic Farms: Methodological Elements

Many typologies of organic farms exist but they fail to take into account diversity, i.e. the combination of productions, which is a core principle in agroecology.Our aims were multifold: i) increase the knowledge of the organic farms (OF) ii) better characterize organic systems in terms of diversity, iii) analyze the territorial distribution of diversity types, and iv) compare diversity between conventional farms (CF) and OF.The French Observatory of Organic Agriculture (ONAB) database from Agence Bio was used. It collects data from all French organic farms and provides detail on surfaces and livestock (about 200 species).We explored complementary methods to build a classification able to reflect the type and level of diversity within the farms’ systems, and to take into account their localization. Nevertheless it was challenging and further work is needed to improve methods to better characterize organic systems with this focus on diversity

Factor VIII-von Willebrand Factor Complex Inhibits Osteoclastogenesis and Controls Cell Survival

Factor VIII-von Willebrand factor (FVIII·vWF) complex, a molecule involved in coagulation, can be physically associated with osteoprotegerin (OPG). OPG is an anti-osteoclastic protein and a soluble receptor for the proapoptotic protein TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), suggesting a potential role of FVIII·vWF complex in bone and cancer biology. We, thus, assessed the effects of FVIII·vWF complex on osteoclastogenesis and cell survival. We first evidenced that FVIII·vWF complex inhibited RANKL-induced osteoclastogenesis and enhanced the inhibitory effect of OPG. Interestingly, we revealed by surface plasmon resonance that FVIII·vWF complex bound to RANKL, whereas recombinant FVIII and vWF did not. By modeling, we showed that the OPG binding domain to the A1 domain of vWF was closely located and partially overlapped to its binding site to RANKL. Then, we demonstrated that FVIII·vWF complex cancelled the inhibitory activity of OPG on TRAIL-induced apoptosis and characterized interactions between these molecules. The present work evidenced a direct activity of FVIII·vWF complex on osteoclasts and on induced cell apoptosis, pointing out its potential involvement in physiological bone remodeling or in bone damages associated with severe hemophilia and cancer development

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

Spanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD

The Spanish COPD Guidelines (GesEPOC) were first published in 2012, and since then have undergone a series of updates incorporating new evidence on the diagnosis and treatment of COPD. GesEPOC was drawn up in partnership with scientific societies involved in the treatment of COPD and the Spanish Patients' Forum. Their recommendations are based on an evaluation of the evidence using GRADE methodology, and a narrative description of the evidence in areas in which GRADE cannot be applied. In this article, we summarize the recommendations on the pharmacological treatment of stable COPD based on 9 PICO questions. COPD treatment is a 4-step process: 1) diagnosis, 2) determination of the risk level, 3) initial and subsequent inhaled therapy, and 4) identification and management of treatable traits. For the selection of inhaled therapy, high-risk patients are divided into 3 phenotypes: non-exacerbator, eosinophilic exacerbator, and non-eosinophilic exacerbator. Some treatable traits are general and should be investigated in all patients, such as smoking or inhalation technique, while others affect severe patients in particular, such as chronic hypoxemia and chronic bronchial infection. COPD treatment is based on long-acting bronchodilators with single agents or in combination, depending on the patient's risk level. Eosinophilic exacerbators must receive inhaled corticosteroids, while non-eosinophilic exacerbators require a more detailed evaluation to choose the best therapeutic option. The new GesEPOC also includes recommendations on the withdrawal of inhaled corticosteroids and on indications for alpha-1 antitrypsin treatment. GesEPOC offers a more individualized approach to COPD treatment tailored according to the clinical characteristics of patients and their level of complexity.Peer reviewe

Optimization of Suture-Free Laser-Assisted Vessel Repair by Solder-Doped Electrospun Poly(ε-caprolactone) Scaffold

Poor welding strength constitutes an obstacle in the clinical employment of laser-assisted vascular repair (LAVR) and anastomosis. We therefore investigated the feasibility of using electrospun poly(ε-caprolactone) (PCL) scaffold as reinforcement material in LAVR of medium-sized vessels. In vitro solder-doped scaffold LAVR (ssLAVR) was performed on porcine carotid arteries or abdominal aortas using a 670-nm diode laser, a solder composed of 50% bovine serum albumin and 0.5% methylene blue, and electrospun PCL scaffolds. The correlation between leaking point pressures (LPPs) and arterial diameter, the extent of thermal damage, structural and mechanical alterations of the scaffold following ssLAVR, and the weak point were investigated. A strong negative correlation existed between LPP and vessel diameter, albeit LPP (484 ± 111 mmHg) remained well above pathophysiological pressures. Histological analysis revealed that thermal damage extended into the medial layer with a well-preserved internal elastic lamina and endothelial cells. Laser irradiation of PCL fibers and coagulation of solder material resulted in a strong and stiff scaffold. The weak point of the ssLAVR modality was predominantly characterized by cohesive failure. In conclusion, ssLAVR produced supraphysiological LPPs and limited tissue damage. Despite heat-induced structural/mechanical alterations of the scaffold, PCL is a suitable polymer for weld reinforcement in medium-sized vessel ssLAVR

Spanish COPD Guidelines (GesEPOC) 2021 Update Diagnosis and Treatment of COPD Exacerbation Syndrome

[ES] En este artículo se presentan las recomendaciones sobre el diagnóstico y tratamiento del síndrome de agudización de la enfermedad pulmonar obstructiva crónica (EPOC) (SAE) de GesEPOC 2021. Como principales novedades, la guía propone una definición y aproximación sindrómica, una nueva clasificación de gravedad y el reconocimiento de diferentes rasgos tratables (RT), lo que supone un nuevo paso hacia la medicina personalizada. La evaluación de la evidencia se realiza mediante la metodología Grading of Recommendations Assessment, Development and Evaluation (GRADE), con la incorporación de seis nuevas preguntas con enfoque paciente, intervención, comparación y resultados (PICO). El proceso diagnóstico comprende cuatro etapas: 1) establecer el diagnóstico del SAE, 2) valorar la gravedad del episodio, 3) identificar el factor desencadenante y 4) abordar los RT. En este proceso diagnóstico se diferencia una aproximación ambulatoria, en la que se recomienda incluir una batería básica de pruebas y una hospitalaria, más exhaustiva, en la que se contempla el estudio de diferentes biomarcadores y pruebas de imagen. El tratamiento broncodilatador destinado al alivio inmediato de los síntomas se considera esencial para todos los pacientes, mientras que el uso de antibióticos, corticoides sistémicos, oxigenoterapia, ventilación asistida o el tratamiento de las comorbilidades variará en función de la gravedad y de los posibles RT. El empleo de antibióticos estará especialmente indicado ante un cambio en el color del esputo, cuando se requiera asistencia ventilatoria, en los casos que cursen con neumonía y también para aquellos con proteína-C reactiva elevada (≥ 20 mg/L). Los corticoides sistémicos se recomiendan en el SAE que necesita ingreso y se sugieren en el SAE moderado. La eficacia de estos fármacos es mayor en pacientes con recuento de eosinófilos en sangre ≥ 300 células/mm3. La ventilación mecánica no invasiva en fase aguda se establece fundamentalmente para pacientes con SAE que cursen con acidosis respiratoria, a pesar del tratamiento inicial.[EN] This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm3. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.Peer reviewe