A Randomized, Controlled Trial of Catheter-Related Infectious Event Rates Using Antibiotic-Impregnated Catheters Versus Conventional Catheters in Pediatric Cardiovascular Surgery Patients

We conducted a randomized, controlled clinical trial to determine whether a difference in catheter-associated blood stream infection (CABSI) incidence existed between children who underwent cardiac surgery and had a central venous catheter impregnated with minocycline and rifampin versus those who had a conventional, nonimpregnated catheter after cardiac surgery. Due to a lower number of infections than expected, the study was terminated early. Among 288 evaluable patients, the rates of CABSI and line-related complications were similar between the 2 groups

Utilization of inhaled nitric oxide after surgical repair of truncus arteriosus: A multicenter analysis

BackgroundElevated pulmonary vascular resistance (PVR) is common following repair of truncus arteriosus. Inhaled nitric oxide (iNO) is an effective yet costly therapy that is frequently implemented postoperatively to manage elevated PVR.ObjectivesWe aimed to describe practice patterns of iNO use in a multicenter cohort of patients who underwent repair of truncus arteriosus, a lesion in which recovery is often complicated by elevated PVR. We also sought to identify patient and center factors that were more commonly associated with the use of iNO in the postoperative period.DesignRetrospective cohort study.Setting15 tertiary care pediatric referral centers.PatientsAll infants who underwent definitive repair of truncus arteriosus without aortic arch obstruction between 2009 and 2016.InterventionsDescriptive statistics were used to demonstrate practice patterns of iNO use. Bivariate comparisons of characteristics of patients who did and did not receive iNO were performed, followed by multivariable mixed logistic regression analysis using backward elimination to identify independent predictors of iNO use.Main ResultsWe reviewed 216 patients who met inclusion criteria, of which 102 (46%) received iNO in the postoperative period: 69 (68%) had iNO started in the operating room and 33 (32%) had iNO initiated in the ICU. Median duration of iNO use was 4 days (range: 1‐21 days). In multivariable mixed logistic regression analysis, use of deep hypothermic circulatory arrest (odds ratio: 3.2; 95% confidence interval: 1.2, 8.4) and center (analyzed as a random effect, p = .02) were independently associated with iNO use.ConclusionsIn this contemporary multicenter study, nearly half of patients who underwent repair of truncus arteriosus received iNO postoperatively. Use of iNO was more dependent on individual center practice rather than patient characteristics. The study suggests a need for collaborative quality initiatives to determine optimal criteria for utilization of this important but expensive therapy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152533/1/chd12849_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152533/2/chd12849.pd

Multicenter Analysis of Early Childhood Outcomes Following Repair of Truncus Arteriosus

Background Literature describing morbidity and mortality following truncus arteriosus repair is predominated by single-center reports. We created and analyzed a multicenter dataset to identify risk factors for late mortality and right ventricle-to-pulmonary artery (RV-PA) conduit reintervention for this patient population. Methods We retrospectively collected data on children who underwent repair of truncus arteriosus without concomitant arch obstruction at 15 centers between 2009 and 2016. Cox regression survival analysis was conducted to determine risk factors for late mortality, defined as death occurring after hospital discharge and greater than 30 days after surgery. Probability of any RV-PA conduit reintervention was analyzed over time using Fine-Gray modelling. Results We reviewed 216 patients, with median follow-up of 2.9 years (range:0.1-8.8). Operative mortaility occurred in 15 patients (7%). Of the 201 survivors, there were 14 (7%) late deaths. DiGeorge syndrome (HR:5.4; 95%CI:1.6-17.8) and need for postoperative tracheostomy (HR:5.9; 95%CI:1.8-19.4) were identified as independent risk factors for late mortality. At least one RV-PA conduit catheterization or surgical reintervention was performed in 109 patients (median time to reintervention:23 months, range:0.3-93). Risk factors for reintervention included use of pulmonary or aortic homografts versus Contegra® bovine jugular vein conduits (HR:1.9; 95%CI:1.2,3.1) and smaller conduit size (HR per mm/m2:1.05; 95%CI:1.03,1.08). Conclusions In a multicenter dataset, DiGeorge syndrome and need for tracheostomy postoperatively were found to be independent risk factors for late mortality after repair of truncus arteriosus, while risk of conduit reintervention was independently influenced by both initial conduit type and size

Trawl fishing impacts on the status of seabed fauna in diverse regions of the globe

Bottom trawl fishing is a controversial activity. It yields about a quarter of the world's wild seafood, but also has impacts on the marine environment. Recent advances have quantified and improved understanding of large-scale impacts of trawling on the seabed. However, such information needs to be coupled with distributions of benthic invertebrates (benthos) to assess whether these populations are being sustained under current trawling regimes. This study collated data from 13 diverse regions of the globe spanning four continents. Within each region, we combined trawl intensity distributions and predicted abundance distributions of benthos groups with impact and recovery parameters for taxonomic classes in a risk assessment model to estimate benthos status. The exposure of 220 predicted benthos-group distributions to trawling intensity (as swept area ratio) ranged between 0% and 210% (mean = 37%) of abundance. However, benthos status, an indicator of the depleted abundance under chronic trawling pressure as a proportion of untrawled state, ranged between 0.86 and 1 (mean = 0.99), with 78% of benthos groups > 0.95. Mean benthos status was lowest in regions of Europe and Africa, and for taxonomic classes Bivalvia and Gastropoda. Our results demonstrate that while spatial overlap studies can help infer general patterns of potential risk, actual risks cannot be evaluated without using an assessment model that incorporates trawl impact and recovery metrics. These quantitative outputs are essential for sustainability assessments, and together with reference points and thresholds, can help managers ensure use of the marine environment is sustainable under the ecosystem approach to management

Society and Learning Research Priority Area - Research share September 2021

The session, held in September 2021, is an introduction to the work of Society and Leaning Research Priority Area (RPA), in which we examine the nature and role of the RPA as well as the ways in which it supports research in the university. The largest part of the event is an opportunity for staff to share a slide on their research, including the focus of the work, ongoing and potential projects, and opportunities for others to get involved

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression), are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use discounted as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens

Critical Infrastructure and Cyber Security

We were tasked by CENTRA Technology, Inc., to create a methodology that could be used to prioritize critical cyber assets in the United States. We have answered that call by developing a user-friendly, consequence-based methodology that requires end users to carefully consider their cyber assets' contributions to vital missions of national security, economic security, and public safety. The user will be able to clearly visualize the potential impact of a loss of cyber assets on those three indicators vis-a-vis one another, which is especially important in the midst of the current budgetary uncertainty in Washington. In this study, we present our definitions of the three indicators; an overview of the eighteen sectors of critical infrastructure and commonalities and the characteristics of their operating systems; a brief review of the literature on cyber security to date; and, of course, a thorough discussion of the intricacies of how our methodology works.CENTRA Technolog