Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Galectin-1: Biphasic growth regulation of Leydig tumor cells

Galectin-1 (Gal-1) is a widely expressed β-galactoside-binding protein that exerts pleiotropic biological functions. To gain insight into the potential role of Gal-1 as a novel modulator of Leydig cells, we investigated its effect on the growth and death of MA-10 tumor Leydig cells. In this study, we identified cytoplasmic Gal-1 expression in these tumor cells by cytofluorometry. DNA fragmentation, caspase-3, -8, and -9 activation, loss of mitochondrial membrane potential (ΔΨ m), cytochrome c (Cyt c) release, and FasL expression suggested that relatively high concentrations of exogenously added recombinant Gal-1 (rGal-1) induced apoptosis by the mitochondrial and death receptor pathways. These pathways were independently activated, as the presence of the inhibitor of caspase-8 or -9 only partially prevented Gal-1-effect. On the contrary, low concentrations of Gal-1 significantly promoted cell proliferation, without inducing cell death. Importantly, the presence of the disaccharide lactose prevented Gal-1 effects, suggesting the involvement of the carbohydrate recognition domain (CRD). This study provides strong evidence that Gal-1 is a novel biphasic regulator of Leydig tumor cell number, suggesting a novel role for Gal-1 in the reproductive physiopathology. © Copyright 2006 Oxford University Press.Fil:Troncoso, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Patrignani, Z.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Pignataro, O.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

eEdad 40Ar/39Ar para la biota de plantas, anuros e insectos del Eoceno Temprano de Pampa de Jones (Formación Huitrera, provincia del Neuquén, Argentina)

The Pampa de Jones fossil site, a stratigraphically isolated roadcut near the northeastern shore of Nahuel Huapi Lake in Neuquén Province, Argentina, holds a rich fossil biota including a macroflora, a microflora, insects, and most famously, an ontogenetic series of pipid frogs. The site exposes tuffaceous mudstone and sandstone beds of probable lacustrine origin, considered to belong to the volcanic Huitrera Formation. However, there have been no reliable age constraints for the fossil assemblage. We undertook laser fusion analyses of sanidine and biotite crystals occurring in a tuff layer found 4.4 m above the main fossil horizon. Twentyeight sanidine crystals yielded an 40ArZ39Ar age of 54.24 ± 0.45 Ma that is preferred over our biotite age of 53.64 ± 0.35 Ma. Pampa de Jones is thus the oldest well-dated Eocene fossil site in Patagonia, predating two other recently 40Ar/39Ar-dated sites: Laguna del Hunco (51.91 ± 0.22 Ma) and Rio Pichileufu (47.46 ± 0.05 Ma). The improved age control makes possible a finer scale of evolutionary hypothesis testing and turnover analysis in the region. The age is concordant with the site's placement in the Huitrera Formation and a depositional origin related to Early Paleogene arc volcanism, and it correlates to an interval of significant climate fluctuations following the Paleocene-Eocene boundary. ©Asociación Paleontológica Argentina.La localidad de Pampa de Jones es un afloramiento estratigráficamente aislado, cercano a la costa noreste del Lago Nahuel Huapi en la Provincia del Neuquén, Argentina. Contiene una rica biota fósil que incluye macroflora, microflora, insectos y una reconocida serie ontogenética de pípidos. La secuencia estratigráfica consiste de fangolitas y areniscas tufáceas de probable origen lacustre, asignada a la Formación Huitrera. La ausencia de datos geocronológicos directos ha impedido la estimación de edades confiables para esta paleobiota. En este trabajo se analizan por fusión láser los cristales de sanidina y biotita presentes en un nivel de toba ubicado a 4.4 m por encima del principal horizonte fosilífero. Veintiocho cristales de sanidina arrojaron una edad 40Ar/39Ar de 54.24 ± 0.45 Ma, la cual se prefiere a la edad de 53.64 ± 0.35 Ma estimada a partir de la biotita. La biota de Pampa de Jones es la más antigua del Eoceno de Patagonia datada radiométricamente, y precede a las dos localidades Eocenas datadas en la región: Laguna del Hunco (51.91 ± 0.22 Ma) y Río Pichileufú (47.46 ± 0.05 Ma). El control cronológico ajustado permitirá evaluar hipótesis evolutivas y analizar recambios en la región con una mayor resolución temporal. La edad obtenida concuerda con la ubicación de la secuencia dentro de la Formación Huitrera y con el origen de los depósitos asociados al volcanismo de arco del Paleógeno temprano, y se correlaciona con un lapso de significativas fluctuaciones climáticas ocurridas con posterioridad al pasaje Paleoceno-Eoceno.Fil: Wilf, Peter. State University of Pennsylvania; Estados UnidosFil: Singer, Brad S.. University of Wisconsin; Estados UnidosFil: Zamaloa, María del Carmen. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Johnson, Kirk R.. Denver Museum of Nature & Science; Estados UnidosFil: Cúneo, Néstor Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; Argentin

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically

Safety of hospital discharge before return of bowel function after elective colorectal surgery

© 2020 BJS Society Ltd Published by John Wiley & Sons LtdBackground: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P < 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients