Multicenter Validation of the Vasoactive-Ventilation-Renal Score as a Predictor of Prolonged Mechanical Ventilation After Neonatal Cardiac Surgery

Objectives: We sought to validate the Vasoactive-Ventilation-Renal score, a novel disease severity index, as a predictor of outcome in a multicenter cohort of neonates who underwent cardiac surgery. Design: Retrospective chart review. Setting: Seven tertiary-care referral centers. Patients: Neonates defined as age less than or equal to 30 days at the time of cardiac surgery. Interventions: Ventilation index, Vasoactive-Inotrope Score, serum lactate, and Vasoactive-Ventilation-Renal score were recorded for three postoperative time points: ICU admission, 6 hours, and 12 hours. Peak values, defined as the highest of the three measurements, were also noted. Vasoactive-Ventilation-Renal was calculated as follows: ventilation index + Vasoactive-Inotrope Score + Δ creatinine (change in creatinine from baseline × 10). Primary outcome was prolonged duration of mechanical ventilation, defined as greater than 96 hours. Receiver operative characteristic curves were generated, and abilities of variables to correctly classify prolonged duration of mechanical ventilation were compared using area under the curve values. Multivariable logistic regression modeling was also performed. Measurements and Main Results: We reviewed 275 neonates. Median age at surgery was 7 days (25th–75th percentile, 5–12 d), 86 (31%) had single ventricle anatomy, and 183 (67%) were classified as Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Category 4 or 5. Prolonged duration of mechanical ventilation occurred in 89 patients (32%). At each postoperative time point, the area under the curve for prolonged duration of mechanical ventilation was significantly greater for the Vasoactive-Ventilation-Renal score as compared to the ventilation index, Vasoactive-Inotrope Score, and serum lactate, with an area under the curve for peak Vasoactive-Ventilation-Renal score of 0.82 (95% CI, 0.77–0.88). On multivariable analysis, peak Vasoactive-Ventilation-Renal score was independently associated with prolonged duration of mechanical ventilation, odds ratio (per 1 unit increase): 1.08 (95% CI, 1.04–1.12). Conclusions: In this multicenter cohort of neonates who underwent cardiac surgery, the Vasoactive-Ventilation-Renal score was a reliable predictor of postoperative outcome and outperformed more traditional measures of disease complexity and severity

Extubation Failure after Neonatal Cardiac Surgery: A Multicenter Analysis

Objectives To describe the epidemiology of extubation failure and identify risk factors for its occurrence in a multicenter population of neonates undergoing surgery for congenital heart disease. Study design We conducted a prospective observational study of neonates ≤30 days of age who underwent cardiac surgery at 7 centers within the US in 2015. Extubation failure was defined as reintubation within 72 hours of the first planned extubation. Risk factors were identified with the use of multivariable logistic regression analysis and reported as OR with 95% CIs. Multivariable logistic regression analysis was conducted to examine the relationship between extubation failure and worse clinical outcome, defined as hospital length of stay in the upper 25% or operative mortality. Results We enrolled 283 neonates, of whom 35 (12%) failed their first extubation at a median time of 7.5 hours (range 1-70 hours). In a multivariable model, use of uncuffed endotracheal tubes (OR 4.6; 95% CI 1.8-11.6) and open sternotomy of 4 days or more (OR 4.8; 95% CI 1.3-17.1) were associated independently with extubation failure. Accordingly, extubation failure was determined to be an independent risk factor for worse clinical outcome (OR 5.1; 95% CI 2-13). Conclusions In this multicenter cohort of neonates who underwent surgery for congenital heart disease, extubation failure occurred in 12% of cases and was associated independently with worse clinical outcome. Use of uncuffed endotracheal tubes and prolonged open sternotomy were identified as independent and potentially modifiable risk factors for the occurrence of this precarious complication

Near-Infrared Spectroscopy for Prediction of Extubation Success after Neonatal Cardiac Surgery

Introduction: Reliable predictors of extubation readiness are needed and may reduce morbidity related to extubation failure. We aimed to examine the relationship between changes in pre-extubation near-infrared spectroscopy measurements from baseline and extubation outcomes after neonatal cardiac surgery. Materials and Methods: In this retrospective cross-sectional multi-centre study, a secondary analysis of prospectively collected data from neonates who underwent cardiac surgery at seven tertiary-care children’s hospitals in 2015 was performed. Extubation failure was defined as need for re-intubation within 72 hours of the first planned extubation attempt. Near-infrared spectroscopy measurements obtained before surgery and before extubation in patients who failed extubation were compared to those of patients who extubated successfully using t-tests. Results: Near-infrared spectroscopy measurements were available for 159 neonates, including 52 with single ventricle physiology. Median age at surgery was 6 days (range: 1–29 days). A total of 15 patients (9.4 %) failed extubation. Baseline cerebral and renal near-infrared spectroscopy measurements were not statistically different between those who were successfully extubated and those who failed, but pre-extubation cerebral and renal values were significantly higher in neonates who extubated successfully. An increase from baseline to time of extubation values in cerebral oximetry saturation by ≥ 5 % had a positive predictive value for extubation success of 98.6 % (95%CI: 91.1–99.8 %). Conclusion: Pre-extubation cerebral near-infrared spectroscopy measurements, when compared to baseline, were significantly associated with extubation outcomes. These findings demonstrate the potential of this tool as a valuable adjunct in assessing extubation readiness after paediatric cardiac surgery and warrant further evaluation in a larger prospective study

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

PMCID: PMC3754866Rockefeller University Press grants the public the non-exclusive right to copy, distribute, or display this Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts