732-1 An Institutional Experience with Second and Third Stage Palliative Procedures for Hypoplastic Left Heart Syndrome: The Impact of the Bidirectional Cavopulmonary Shunt

We reviewed 71 consecutive pts who underwent stage II and III operations following stage I palliation for hypoplastic left heart syndrome (HLHS) at our institution since 1983. 6 surgeons participated in the care of these pts. Follow-up is 97% complete. We examined 17 potential risk factors for mortality, including preoperative anatomic and physiologic factors, and procedural features of the stage II operation. Multivariate analysis revealed that the only significant risk factor for stage II mortality was the performance of a non-fenestrated completion Fontan procedure (p<0.001). There were 9 hospital deaths (69%) in the 13 pts undergoing the Fontan procedure at stage II. In contrast, 49 pts underwent bidirectional cavopulmonary shunting (47) or hemi-Fontan procedure(2) as an intermediate step to the Fontan procedure with 4 (8%) early deaths. The first bidirectional cavopulmonary shunt was performed in this population in 1988. Median age at this stage II procedure was 8.4 months. Surgical augmentation of the pulmonary arteries was performed in 18 (37%) pts at the time of stage II surgery and was not associated with increased operative risk. Also, HLHS anatomic subtype was not a risk factor for stage II mortality or pre-stage III attrition. There have been 2 (4%) intermediate deaths prior to the performance of a stage III procedure, which at our institution is the fenestrated Fontan procedure. This has been performed in 25 pts at a median age of 30 months with 1 early death and no mortality at a median follow-up of 22 months. There are presently 34 HLHS pts who have modified Fontan anatomy following a course of surgical palliation performed entirely at this institution. Follow-up in this group ranges up to 92 months, with a median of 28 months. 33 of these patients are NYHA class 1 or 2.2 pts have required pacemaker implantation, but there have otherwise been no surgical reinterventions in pts who have completed palliation. We conclude that the incorporation of the bidirectional cavopulmonary shunt into a course of surgical palliation for HLHS has dramatically reduced mortality in this challenging group of pts, allowing them to undergo the modified fenestrated Fontan procedure with low operative mortality and good intermediate outcome

Self-reported dual sensory impairment and related factors: a European population-based cross-sectional survey

International audienceBackground Data on population-based self-reported dual vision and hearing impairment are sparse in Europe. We aimed to investigate self-reported dual sensory impairment (DSI) in European population. Methods A standardised questionnaire was used to collect medical and socio-economic data among individuals aged 15 years or more in 29 European countries. Individuals living in collective households or in institutions were excluded from the survey. Results Among 296 677 individuals, the survey included 153 866 respondents aged 50 years old or more. The crude prevalence of DSI was of 7.54% (7.36–7.72). Among individuals aged 60 or more, 9.23% of men and 10.94% of women had DSI. Eastern and southern countries had a higher prevalence of DSI. Multivariable analyses showed that social isolation and poor self-rated health status were associated with DSI with ORs of 2.01 (1.77–2.29) and 2.33 (2.15–2.52), while higher income was associated with lower risk of DSI (OR of 0.83 (0.78–0.89). Considering country-level socioeconomic factors, Human Development Index explained almost 38% of the variance of age-adjusted prevalence of DSI. Conclusion There are important differences in terms of prevalence of DSI in Europe, depending on socioeconomic and medical factors. Prevention of DSI does represent an important challenge for maintaining quality of life in elderly population

Low serum zinc levels predict presence of depression symptoms, but not overall disease outcome, regardless of ATG16L1 genotype in Crohn's disease patients.

Zinc deficiency (ZD) in Crohn's disease (CD) is considered a frequent finding and may exacerbate CD activity. ZD is associated with depression in non-CD patients. We aimed to assess the prevalence of ZD in CD patients in clinical remission, its association with mood disturbances and to analyze a potential impact on future disease course. Zinc levels from CD patients in clinical remission at baseline and an uncomplicated disease course within the next 3 years ( <i>n</i> = 47) were compared with those from patients developing complications ( <i>n</i> = 50). Baseline symptoms of depression and anxiety were measured with the Hospital Anxiety and Depression scale. Mean zinc level in the 97 patients (40.4 ± 15.7 years, 44.3% males) was 18.0 ± 4.7 μmol/l. While no ZD (<11 μmol/l) was observed, we found low zinc levels (<15.1 μmol/l) in 28 patients (28.9%). Males had higher zinc levels compared with females (19.4 ± 5.7 <i>versus</i> 16.8 ± 3.3, <i>p</i> = 0.006). Patients with low zinc levels more often reported depression symptoms compared with patients with higher levels (27.3 <i>versus</i> 9.4%, <i>p</i> = 0.047). In a multivariate analysis, zinc levels were an independent negative predictor for depression symptoms [odds ratio (OR) 0.727, 95% confidence interval (CI) 0.532-0.993, <i>p</i> = 0.045]. Zinc levels of patients with a complicated disease course were not different from those of patients without (17.7 ± 4.3 <i>versus</i> 18.3 ± 5.1, n.s.). Baseline zinc levels did not predict disease outcome regardless of ATG16L1 genotype. Low-normal zinc levels were an independent predictor for the presence of depression symptoms in CD patients. Zinc levels at baseline did not predict a complicated disease course, neither in CD patients overall, nor ATG16L1 <sup>T300A</sup> carriers

Self-reported visual difficulties in Europe and related factors: a European population-based cross-sectional survey.

PURPOSE: There is a relative paucity of self-reported vision problems data in European countries. METHODS: In this context, we investigated self-reported vision problems through European Health Interview Survey 2, a cross-sectional European population survey based on a standardized questionnaire including 147 medical, demographic and socioeconomic variables applied to non-institutionalized individuals aged 15 years or more in 28 European countries, in addition to Iceland and Norway. RESULTS: The survey included 311 386 individuals (54.18% women), with overall crude prevalence of self-reported vision problems of 2.07% [95% CI; 2.01-2.14]. Among them, 1.70 % [1.61-1.78] of men, 2.41% [2.31-2.51] of women and 4.71% [4.53-4.89] of individuals aged 60 or more reported to have a lot of vision problems or to be not able to see. The frequency of self-reported vision problems was the highest in Eastern European countries with values of 2.43% [2.30-2.56]. In multivariate analyses, limiting long-standing illness, depression, daily smoking, lack of physical activity, lower educational level and social isolation were associated with self-reported vision problems with ORs of 2.66 [2.42-2.92], 2.16 [2.01-2.32], 1.11 [1.01-1.23], 1.31 [1.21-1.42], 1.29 [1.19-1.40] and 1.45 [1.26-1.67], respectively, while higher income was associated with less self-reported vision problems with OR of 0.80 [0.73-0.86]. CONCLUSIONS: This study demonstrated inequalities in terms of prevalence of self-reported vision problems in Europe, with higher prevalence in Eastern European countries and among women and older individuals

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy

Why we need sustainable networks bridging countries, disciplines, cultures and generations for Aquatic Biomonitoring 2.0: A Perspective Derived From the DNAqua-Net COST Action

Aquatic biomonitoring has become an essential task in Europe and many other regions as a consequence of strong anthropogenic pressures affecting the health of lakes, rivers, oceans and groundwater. A typical assessment of the environmental quality status, such as it is required by European but also North American and other legislation, relies on matching the composition of assemblages of organisms identified using morphological criteria present in aquatic ecosystems to those expected in the absence of anthropogenic pressures. Through decade-long and difficult intercalibration exercises among networks of regulators and scientists in European countries, a pragmatic biomonitoring approach was developed and adopted, which now produces invaluable information. Nonetheless, this approach is based on several hundred different protocols, making it susceptible to issues with comparability, scale and resolution. Furthermore, data acquisition is often slow due to a lack of taxonomic experts for many taxa and regions and time-consuming morphological identification of organisms. High-throughput genetic screening methods such as (e)DNA metabarcoding have been proposed as a possible solution to these shortcomings. Such "next-generation biomonitoring", also termed "biomonitoring 2.0", has many advantages over the traditional approach in terms of speed, comparability and costs. It also creates the potential to include new bioindicators and thereby further improves the assessment of aquatic ecosystem health. However, several major conceptual and technological challenges still hinder its implementation into legal and regulatory frameworks. Academic scientists sometimes tend to overlook legal or socioeconomic constraints, which regulators have to consider on a regular basis. Moreover, quantification of species abundance or biomass remains a significant bottleneck to releasing the full potential of these approaches. Here, we highlight the main challenges for next-generation aquatic biomonitoring and outline principles and good practicCOST - European Cooperation in Science and Technology(CA15219). COST Action DNAqua-Net (CA15219), supported by the COST (European Cooperation in Science and Technology) programm

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.)

A pair of Sub-Neptunes transiting the bright K-dwarf TOI-1064 characterised with CHEOPS

Funding: TGW, ACC, and KH acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant ST/R003203/1.We report the discovery and characterization of a pair of sub-Neptunes transiting the bright K-dwarf TOI-1064 (TIC 79748331), initially detected in the Transiting Exoplanet Survey Satellite (TESS) photometry. To characterize the system, we performed and retrieved the CHaracterising ExOPlanets Satellite (CHEOPS), TESS, and ground-based photometry, the High Accuracy Radial velocity Planet Searcher (HARPS) high-resolution spectroscopy, and Gemini speckle imaging. We characterize the host star and determine Teff,⋆=4734±67K⁠, R⋆=0.726±0.007R⊙⁠, and M⋆=0.748±0.032M⊙⁠. We present a novel detrending method based on point spread function shape-change modelling and demonstrate its suitability to correct flux variations in CHEOPS data. We confirm the planetary nature of both bodies and find that TOI-1064 b has an orbital period of Pb = 6.44387 ± 0.00003 d, a radius of Rb = 2.59 ± 0.04 R⊕, and a mass of Mb=13.5+1.7−1.8 M⊕, whilst TOI-1064 c has an orbital period of Pc=12.22657+0.00005−0.00004 d, a radius of Rc = 2.65 ± 0.04 R⊕, and a 3σ upper mass limit of 8.5 M⊕. From the high-precision photometry we obtain radius uncertainties of ∼1.6 per cent, allowing us to conduct internal structure and atmospheric escape modelling. TOI-1064 b is one of the densest, well-characterized sub-Neptunes, with a tenuous atmosphere that can be explained by the loss of a primordial envelope following migration through the protoplanetary disc. It is likely that TOI-1064 c has an extended atmosphere due to the tentative low density, however further radial velocities are needed to confirm this scenario and the similar radii, different masses nature of this system. The high-precision data and modelling of TOI-1064 b are important for planets in this region of mass–radius space, and it allow us to identify a trend in bulk density–stellar metallicity for massive sub-Neptunes that may hint at the formation of this population of planets.Publisher PDFPeer reviewe

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe