Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation.

SARS-CoV-2 induces a hyperinflammatory reaction due to the excessive release of cytokines during the immune response. The bacterial endotoxin lipopolysaccharide (LPS) contributes to the low-grade inflammation associated with the metabolic syndrome, enhancing the hyperinflammatory reaction induced by the SARS-CoV-2 infection. The intake of sodium nitrate, a precursor of nitrite and nitric oxide, influences the antioxidant and pro-inflammatory gene expression profile after immune stimulation with LPS in peripheral blood mononuclear cells from metabolic syndrome patients. We aimed to assess the inflammatory and antioxidant responses of immune cells from metabolic syndrome patients to exposure to the SARS-CoV-2 spike protein (S protein) together with LPS and the effect of nitrite in these responses. Whole blood samples obtained from six metabolic syndrome patients were cultured for 16 h at 37 °C with four different media: control medium, control medium plus LPS (100 ng/mL), control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL), and control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL) plus nitrite (5 µM). Immune stimulation with the LPS/S protein enhanced nitrate biosynthesis from nitrite oxidation and probably from additional organic precursors. In vitro incubations with the LPS/S protein enhanced the expression and/or release of pro-inflammatory TNFα, IL-6, IL-1ß, and TLR4, as well as the expression of the anti-inflammatory IL-1ra and IL-10 and antioxidant enzymes. Nitrite attenuated the pro- and anti-inflammatory response induced by the S protein without interfering with the activation of TLR4 and antioxidant enzyme expression, raising the possibility that nitrite could have potential as a coadjutant in the treatment of COVID-19.

Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification.

Background: Patients receiving dialysis have high cardiovascular risk in part due to extensive vascular calcification. In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52 weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC). This report examines pharmacokinetic/pharmacodynamic (PK/PD) and exposure-efficacy in CaLIPSO. Methods: We measured hexasodium fytate plasma concentrations (PK) by validated liquid chromatography-mass spectroscopy, and hydroxyapatite crystallization in plasma (PD) by validated spectrophotometry. Analyses included patients evaluable for PK, PD, and CAC change (per-protocol analysis). We developed a simple Emax model for maximum concentration (Cmax) and PD effect, and linear and non-linear Emax models for exposure-efficacy among individual average Cmax and absolute and percent changes in CAC score from baseline to week 52. Results: Among evaluable patients receiving placebo (n = 15), 300 mg (n = 20), or 600 mg (n = 20), average Cmax across visits was not quantifiable (<0.76 µM), 15 µM, and 46 µM, respectively. These results suggest a more-than-proportional increase, without accumulation, with a Cmax ratio of approximately 3 for the doses administered. Average inhibition of hydroxyapatite crystallization was 15%, 61%, and 75%, respectively, and similar across visits. Simple Emax models described 80% maximal effect at exposures >21.9 µM and a plateau in exposure-efficacy above the third quartile of Cmax (≥32 µM). Conclusion: Hexasodium fytate has exposure-dependent effects on hydroxyapatite crystallization and progression of cardiovascular calcification. Simple Emax models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028.

Tratamiento endovascular de aneurismas con anatomía aórtica compleja / Endovascular treatment of aneurysms with complex aortic anatomy

RESUMEN Introducción: la anatomía arterial es la principal limitante para el abordaje aórtico endovascular estándar. Presentamos nuestra experiencia para la reparación endovascular de aneurismas aórticos complejos. Material y métodos: estudio observacional retrospectivo en pacientes con aneurismas complejos (yuxta/pararrenales y toracoabdominales) tratados en forma consecutiva mediante: endoprótesis fenestradas (FEVAR), ramificadas (BEVAR), con EndoAnchors (ESAR), o en chimenea (ChEVAR). La decisión de la técnica fue determinada con base en la anatomía arterial. Resultados: se evaluaron los últimos 50 procedimientos (6 mujeres; edad promedio 71,3 años; diámetro 69,6mm; 3 pacientes con aneurismas complicados), de los cuales 22 recibieron FEVAR (2,8 fenestraciones / paciente), 11 BEVAR, 11 ESAR y 6 ChEVAR (1,8 chimeneas /paciente). La tasa de éxito técnico fue del 100% (ausencia de endoleak I o III con permeabilidad adecuada de los vasos viscerales). A 30 días 3 pacientes fallecieron (6%). Durante el seguimiento, 5 pacientes presentaron oclusión de la arteria renal, repermeabilizada en 4. Cuatro pacientes desarrollaron un endoleak tipo IA (3 ESAR secundarios y un ChEVAR), un paciente un endoleak IC y un cuarto uno IIIB (22%, 3 de los 11 ESAR, ninguno de los FEVAR industriales). En el análisis de supervivencia, la supervivencia global fue del 88,6% al año, y libre de reoperación del 86,5%. Conclusiones: se trata de la primera publicación en nuestro medio que muestra un enfoque global del paciente con un aneurisma de aorta complejo, de acuerdo con sus características anatómicas. Estas tecnologías ya desempeñan un papel primario en el tratamiento de estos pacientes.

ABSTRACT Background: Arterial anatomy is the main limiting factor for standard endovascular aortic (EVAR) approach. We present our experience for endovascular repair of complex aortic aneurysms. Material and Methods: This is a retrospective observational study in patients with complex aneurysms (juxta/pararenal and thoracoabdominal) treated consecutively with: fenestrated (FEVAR), branched (BEVAR), EndoAnchors (ESAR), or chimney (ChEVAR) stents. The decision of the technique was determined based on the arterial anatomy. Results: The last 50 procedures were evaluated (6 women; mean age 71.3 years; diameter 69.6 mm; and 3 patients with complicated aneurysms), among whom 22 received FEVAR (2.8 fenestrated stents/patient), 11 BEVAR, 11 ESAR and 6 ChEVAR (1.8 chimney stents/patient). Technical success rate was 100% (absence of type I or III endoleak with adequate patency of the visceral vessels). Three patients died within the first 30 days (6%). During follow-up, 5 patients presented with renal artery occlusion, treated successfully in 4 cases. Four patients developed type IA endoleak (3 secondary ESAR and one ChEVAR), one patient IC endoleak and almost a quarter of cases type IIIB endoleak (22%, 3 out of 11 patients receiving ESAR, none of the industrial FEVAR group). In survival analysis, overall survival analysis was 88.6% at one year, and 86.5% of cases were free from reoperation. Conclusions: This is the first publication in our setting that shows a global approach to the patient with complex aortic aneurysm, according to the anatomical characteristics. These technologies already play a primary role in the treatment of these patients.

Tratamiento endovascular de aneurismas de arterias viscerales. Experiencia de 10 años en un solo centro / Endovascular treatment of visceral artery aneurysms. A single center 10-year experience

RESUMEN Antecedentes : los aneurismas de arterias viscerales (AAV) tienen una frecuencia baja (0,1 a 2%). Hasta un 25% puede presentarse como rotura, con una alta mortalidad (hasta 70%). La terapia endovascular ha ganado terreno y se recomienda como primera opción según las últimas guías. Hoy en día, es posible adaptarse a casi cualquier anatomía utilizando tecnología cerebral. Objetivo : describir la experiencia y enfoque en el manejo endovascular de AAV, con resultados a corto, mediano y largo plazo. Material y métodos : llevamos a cabo una evaluación retrospectiva de pacientes tratados por AAV verdaderos por vía endovascular en un solo centro entre 2010 y 2020, con un seguimiento mínimo de 6 meses. Resultados : analizamos 19 procedimientos en 18 pacientes (9 hombres y 9 mujeres). La edad promedio fue 61,9 años; el promedio de tiempo de internación fue 1,94 días y el promedio de seguimiento de 40 meses. La arteria más involucrada fue la esplénica (n = 9, 50%). El tamaño aneurismático promedio fue 30,1 mm. La estrategia terapéutica más utilizada fue colocación de diversor de flujo (n = 8, 42,1%). Dos pacientes fueron reintervenidos (11,1%). Las tasas de exclusión completa fueron del 47,4%, 68,4% y 94,7% a los 3, 6 y 12 meses, respectivamente. No hubo casos de mortalidad a 30 días ni mortalidad relacionada con el aneurisma durante el seguimiento. Conclusión : el tratamiento endovascular de los AAV es seguro y eficaz. Sin embargo, se debe contar con la tecnología adecuada, para la planificación preoperatoria y el tratamiento.

ABSTRACT Background : the prevalence of visceral artery aneurysms (VAAs) is low (0.1 to 2%). Up to 25% may present as rupture which is associated with high mortality (up to 70%). Endovascular treatment has gained ground and is even considered the first option according to the most recent recommendations. Nowadays, almost any anatomy can be approached with endovascular techniques used to treat intracranial aneurysms. Objective : the aim of our study was to describe the experience and approach for the endovascular management of VAAs with short-, mid-, and long-term results. Material and methods : we conducted a retrospective evaluation of patients with true VAAs undergoing endovascular treatment in a single center between 2010 and 2020 who were followed up for a minimum of 6 months. Results : we analyzed 19 procedures in 18 patients (9 men and 9 women). Mean age was 61.9 years; mean length of hospital stay was 1.94 days and mean follow-up was 40 months. The splenic artery was the vessel most affected (n = 9, 50%). Mean aneurysm size was 30.1 mm. Flow diversion was the strategy most used (n = 8, 42.1%). Two patients required reintervention (11%). Complete exclusion rate was 38.4%, 47.4%, 68.4% and 94.7% at 3, 6 and 12 months, respectively. There were no cases of mortality within the first 30 days and no aneurysm-related mortality during the follow-up period. Conclusion : endovascular treatment of VAAs is a safe and efficient strategy but requires adequate technology for preoperative planning and treatment.

Polyunsaturated and Saturated Oxylipin Plasma Levels Allow Monitoring the Non-Alcoholic Fatty Liver Disease Progression to Severe Stages.

Hepatic fat accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD). Our aim was to determine the plasma levels of oxylipins, free polyunsaturated fatty acids (PUFA) and markers of lipid peroxidation in patients with NAFLD in progressive stages of the pathology. Ninety 40-60-year-old adults diagnosed with metabolic syndrome were distributed in without, mild, moderate or severe NAFLD stages. The free PUFA and oxylipin plasma levels were determined by the UHPLC-MS/MS system. The plasma levels of oxylipins produced by cyclooxygenases, lipoxygenases and cytochrome P450, such as prostaglandin 2α (PGF2α), lipoxinB4 and maresin-1, were higher in severe NAFLD patients, pointing to the coexistence of both inflammation and resolution processes. The plasma levels of the saturated oxylipins 16-hydroxyl-palmitate and 3-hydroxyl-myristate were also higher in the severe NAFLD patients, suggesting a dysregulation of oxidation of fatty acids. The plasma 12-hydroxyl-estearate (12HEST) levels in severe NAFLD were higher than in the other stages, indicating that the hydroxylation of saturated fatty acid produced by reactive oxygen species is more present in this severe stage of NAFLD. The plasma levels of 12HEST and PGF2α are potential candidate biomarkers for diagnosing NAFLD vs. non-NAFLD. In conclusion, the NAFLD progression can be monitored by measuring the plasma levels of free PUFA and oxylipins characterizing the different NAFLD stages or the absence of this disease in metabolic syndrome patients.

Hacking techniques improve health and nutritional status of nestling White-tailed Eagles.

Birds of prey frequently feature in reintroductions and the hacking technique is typically used. Hacking involves removing large nestlings from donor populations, transferring them to captivity, feeding them ad libitum. Potentially, via the hacking method, the stress of captivity and disruption of parental feeding may be detrimental. Alternatively, the provision of ad libitum food may be advantageous. Although hacking has underpinned reintroduction project successes there has been no research on how the method may affect the health and nutritional status of translocated birds during captivity. We compared blood chemistry data from 55 young White-tailed Eagles, translocated from Norway as part of the species' reintroduction to Scotland, from sampling soon after arriving in captivity and again (≈42 days later) before their release. Numerous significant differences between the first and second samples were found, but no significant interactions showed that the sexes responded similarly to captivity. According to hematological and biochemical metrics, individuals showed several changes during captivity, including in red blood cell parameters, plasma proteins, and white cellular parameters related to the immune system, that indicated improved health status. Captivity with ad libitum food was associated with decreased urea and uric acid values: high values can indicate nutritional stress. Urea values became more normally distributed before release, indicating that ad libitum food had reduced nutritional differences between early nestlings in the season and later ones. Despite plentiful food, both sexes lost body mass before release, suggesting an inherent physiological mechanism to improve flight performance in fledglings. We conclude that hacking improved the health and nutritional status of released eagles which is likely to enable birds to cope with greater costs of exploratory behavior which they may require in reintroduction projects. In this context, we note the absence of survival differences between hacked and wild raptors in previous research.

Enhancing monitoring and transboundary collaboration for conserving migratory species under global change: The priority case of the red kite.

Calls for urgent action to conserve biodiversity under global change are increasing, and conservation of migratory species in this context poses special challenges. In the last two decades the Convention on the Conservation of Migratory Species of Wild Animals (CMS) has provided a framework for several subsidiary instruments including action plans for migratory bird species, but the effectiveness and transferability of these plans remain unclear. Such laws and policies have been credited with positive outcomes for the conservation of migratory species, but the lack of international coordination and on-ground implementation pose major challenges. While research on migratory populations has received growing attention, considerably less emphasis has been given to integrating ecological information throughout the annual cycle for examining strategies to conserve migratory species at multiple scales in the face of global change. We fill this gap through a case study examining the ecological status and conservation of a migratory raptor and facultative scavenger, the red kite (Milvus milvus), whose current breeding range is limited to Europe and is associated with agricultural landscapes and restricted to the temperate zone. Based on our review, conservation actions have been successful at recovering red kite populations within certain regions. Populations however remain depleted along the southern-most edge of the geographic range where many migratory red kites from northern strongholds overwinter. This led us to a forward-looking and integrated strategy that emphasizes international coordination involving researchers and conservation practitioners to enhance the science-policy-action interface. We identify and explore key issues for conserving the red kite under global change, including enhancing conservation actions within and outside protected areas, recovering depleted populations, accounting for climate change, and transboundary coordination in adaptive conservation and management actions. The integrated conservation strategy is sufficiently general such that it can be adapted to inform conservation of other highly mobile species subject to global change.

Fenestrated endovascular aortic aneurysm repair promotes positive infrarenal neck remodeling and greater sac shrinkage compared with endovascular aortic aneurysm repair.

OBJECTIVE: Endovascular aortic aneurysm repair (EVAR) has become the standard of care for abdominal aortic aneurysms (AAAs) in the modern era. Although numerous devices exist for standard infrarenal AAA repair, fenestrated EVAR (fEVAR) offers a minimally invasive alternative to traditional open repair for patients with a short infrarenal neck. Over time, aortic neck dilation can occur, leading to loss of the proximal seal, endoleaks, and AAA sac growth. In the present study, we analyzed aortic remodeling after EVAR vs fEVAR and further evaluated whether fEVAR confers a benefit in terms of sac shrinkage. METHODS: A retrospective review of prospectively collected data from 120 patients who had undergone EVAR was performed. Of these 120 patients, 30 had been treated with fEVAR (Zenith fenestrated; Cook Medical Inc, Bloomington, IN) and 90 patients were treated with EVAR devices (30 each with Endurant [Medtronic, Dublin, Ireland], Excluder [W.L. Gore & Associates, Flagstaff, AZ], and Zenith [Cook Medical Inc]). The demographic data were recorded. Also, anatomic measurements were performed for each patient preoperatively, at 30 days postoperatively, and at the longest follow-up point using three-dimensional reconstruction software. RESULTS: No significant differences were found in demographic data between the four groups. fEVAR had been used more often in aortas with large necks and irregular morphology (P = .004). At the longest follow-up, the suprarenal aorta encompassing 5, 10, and 15 mm above the lowest renal artery had dilated the most for the fEVAR group vs all EVAR groups. However, the infrarenal segment had tended to increase the least, or to even have regressed, for fEVAR compared with all three EVAR groups and was associated with the overall greatest proportion of sac shrinkage for the fEVAR group compared with the Medtronic, Gore, and Cook devices (-13.90% vs -5.75% vs -2.31% vs -4.68%, respectively; P = .025). CONCLUSIONS: Compared with EVAR, the patients treated with fEVAR had experienced greater suprarenal dilation over time, consistent with an overall greater burden of disease in the proximal native aorta. However, the infrarenal segment had dilated significantly less over time in the fEVAR group compared with all three EVAR groups, suggesting that fEVAR might stabilize the infrarenal neck, promoting positive sac remodeling, which was evidenced by the greatest degree of decrease in the largest AAA diameter in the fEVAR group.

ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure.

BACKGROUND: High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). MATERIALS AND METHODOLOGY: The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. RESULTS: The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. CONCLUSIONS: HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.

Metalliferous Mining Pollution and Its Impact on Terrestrial and Semi-terrestrial Vertebrates: A Review.

Metalliferous mining, a major source of metals and metalloids, has severe potential environmental impacts. However, the number of papers published in international peer-reviewed journals seems to be low regarding its effects in terrestrial wildlife. To the best of our knowledge, our review is the first on this topic. We used 186 studies published in scientific journals concerning metalliferous mining or mining spill pollution and their effects on terrestrial and semi-terrestrial vertebrates. We identified the working status of the mine complexes studied, the different biomarkers of exposure and effect used, and the studied taxa. Most studies (128) were developed in former mine sites and 46 in active mining areas. Additionally, although several mining accidents have occurred throughout the world, all papers about effects on terrestrial vertebrates from mining spillages were from Aznalcóllar (Spain). We also observed a lack of studies in some countries with a prominent mining industry. Despite >50% of the studies used some biomarker of effect, 42% of them only assessed exposure by measuring metal content in internal tissues or by non-invasive sampling, without considering the effect in their populations. Most studied species were birds and small mammals, with a negligible representation of reptiles and amphibians. The information gathered in this review could be helpful for future studies and protocols on the topic and it facilitates a database with valuable information on risk assessment of metalliferous mining pollution.

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.

We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele ORMeta=0.83, PMeta=0.000077; PHet=0.61). In addition, we found that each copy of the LRRC55rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; PHet=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; PHet=0.45; PInteraction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the MAFBrs6071980 and CNTN5rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; PHet=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; PHet=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; PHet=0.12; PInteraction=0.032). Mechanistically, we found that subjects carrying the LINC02549rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated.

Dietary Sodium Nitrate Activates Antioxidant and Mitochondrial Dynamics Genes after Moderate Intensity Acute Exercise in Metabolic Syndrome Patients.

Exercise can induce a pro-inflammatory response in aged subjects with metabolic disorders and nitrate supplementation has shown anti-inflammatory effects. We evaluated the influence of dietary nitrate on the response of the antioxidant and mitochondrial dynamics genes to acute exercise in peripheral blood mononuclear cells (PBMCs), as well as the antioxidant and the inflammatory response of PBMCs against immune stimulation. Metabolic syndrome patients participated in a crossover study in which they consumed a beverage containing 16 mM sodium nitrate or a placebo with the same composition without nitrate before performing a submaximal test at 60%-70% of their maximal heart rate for 30 min. The intake of nitrate increased the nitrate plus nitrite plasma levels about 8-fold and induced the upregulation of catalase, superoxide dismutase, glutathione peroxidase, mitofusin 2 and PGC1α in PBMCs after exercise. The gene expression of catalase and TNFα was enhanced by phorbol myristate acetate (PMA) only in the placebo group, while the glutathione peroxidase expression was enhanced by PMA only after nitrate intake. The intake of nitrate by metabolic syndrome patients induces an antioxidant and mitochondrial response to exercise at the same time that it attenuates the pro-inflammatory response to immune stimulation.

Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials.

BACKGROUND: Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning. METHODS: In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation. RESULTS: We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, - 3.43; 95% CI - 5.17 to - 1.69 days, p < 0.001), a shorter duration of total days spent on mechanical ventilation (mean difference, - 2.04; 95% CI - 3.82 to - 0.27 days, p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality. CONCLUSIONS: Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation. TRIAL REGISTRATION: The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.

Temporal trends of inorganic elements in a common kestrel (Falco tinnunculus) population from south west Spain.

Historical variations (1966-2016) in the exposure to inorganic elements in raptors of South West Spain have been little studied. Therefore, uncertainty exists concerning whether environmental or anthropogenic inputs, as well as dietary strategy shift, may cause changes in exposure patterns. To address this gap, essential and non-essential inorganic elements were measured in Common kestrel (Falco tinnunculus) feathers from museum specimens and free-living individuals spanning a 50-year period. Moreover, stable isotopes of δ13C and δ15N were also measured as proxies of Common kestrel feeding ecology over time. In general, all elements showed significant increasing trends overtime, suggesting changes of inputs from local sources. Moreover, δ15N signatures were correlated to the variations in Al, Cr, Cu, Fe, K, Li, Mg, Mn, Ni, P, Pb, Rb, Sr, Ti, V and Zn concentrations, suggesting trophic changes in this kestrel population as well as possible biomagnification processes. Finally, some values of Cr, Mn and Pb were above the threshold concentrations of potential toxicity.

A novel assay to measure calcification propensity: from laboratory to humans.

Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N = 38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Inhibition of CVC was 50-65% with SNF472 3 mg/kg and ~ 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r = 0.628, P = 0.005). In patients with calciphylaxis (N = 14), infusion of SNF472 (~ 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N = 274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r = 0.401, P = 0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors.