Transposition of the great arteries is the most common cyanotic congenital heart defect. Surgical correction usually occurs in the first week of life; presence of restrictive interatrial ...communication and severe hypoxemia warrants urgent intervention with balloon atrial septostomy and medical stabilization prior to surgery. The main objective of this study is to compare the characteristics, outcomes, and mortality risks in patients with transposition of the great arteries who underwent balloon atrial septostomy during their hospitalization versus transposition of the great arteries patients who have not undergone this procedure.
Retrospective analysis of administrative data.
Data from Kids' Inpatient Database complemented with the National Inpatient Sample dataset for the years 1998-2014, this includes data from participating hospitals in 47 U.S. States and the District of Columbia.
Neonates admitted with transposition of the great arteries.
None.
A total of 17,392 neonates with diagnosis of transposition of the great arteries were captured in the databases we used. Male-to-female ratio was 2:1. The rate of balloon atrial septostomy in patients with transposition of the great arteries was 27.7% without significant change over the years. There was no significant difference in mortality between balloon atrial septostomy and no balloon atrial septostomy (6.3% vs 6.7%; p = 0.29). Neonates with balloon atrial septostomy had a two-fold increase in their length of stay compared with no balloon atrial septostomy (16 d vs 7 d; p < 0.0001). Stroke was present in 1.1% of balloon atrial septostomy group versus 0.6% in those who did not have balloon atrial septostomy (odds ratio, 1.85; 95% CI, 1.29-2.65; p < 0.0001). Extracorporeal membrane oxygenation was used more in balloon atrial septostomy group (5.1% vs 3.1%; p < 0.0001).
There was no difference in mortality rate between balloon atrial septostomy and no balloon atrial septostomy patients. The prevalence of the diagnosis of stroke in this study was higher in patients who underwent balloon atrial septostomy. Furthermore, comparison of in-hospital mortality in balloon atrial septostomy and no balloon atrial septostomy revealed increased mortality risk in no balloon atrial septostomy patients transferred from other institution, no balloon atrial septostomy patients supported with extracorporeal membrane oxygenation, and balloon atrial septostomy patients diagnosed with stroke. Finally, length of stay and charges were higher in balloon atrial septostomy patients.
Background and Objectives
The use of inhaled nitric oxide (iNO) in +late preterm and term infants with pulmonary hypertension is Food and Drug Administration (FDA) approved and has improved outcomes ...and survival. iNO use is not FDA approved for preterm infants and previous studies show no mortality benefit. The objectives were 1) to determine the usage of iNO among preterm neonates <35 weeks before and after the 2010 National Institutes of Health consensus statement and 2) to evaluate characteristics and outcomes among preterm neonates who received iNO.
Methods
This is a population‐based cross‐sectional study. Billing and procedure codes were used to determine iNO usage. Data were queried from the National Inpatient Sample from 2004 to 2016. Neonates were included if gestational age was <35 weeks. The epochs were spilt into 2004–2010 (Epoch 1) and 2011–2016 (Epoch 2). Prevalence of iNO use, mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, length of stay, mechanical ventilation, and cost of hospitalization.
Results
There were 4865 preterm neonates <35 weeks who received iNO. There was a significant increase in iNO use during Epoch 2 (p < 0.001). There was significantly higher use in Epoch 2 among neonates small for gestational age (SGA) 2.3% versus 7.2%, congenital heart disease (CHD) 11.1% versus 18.6%, and BPD 35.2% versus 46.8%. Mortality was significantly lower in Epoch 2 19.8% versus 22.7%.
Conclusion
Usage of iNO was higher after the release of the consensus statement. The increased use of iNO among preterm neonates may be targeted at specific high‐risk populations such as SGA and CHD neonates. There was lower mortality in Epoch 2; however, the cost was doubled.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk-based diet (HUM).
In a multicenter retrospective cohort study, ...infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2-3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD).
A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group.
Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.
The objective of this study was to use current national data to evaluate the characteristics and survival trends of preterm infants born with CDH from 2004 to 2014.
Data was queried from the National ...Inpatient Sample (NIS) and KID database from 2004 to 2014. Infants were included if diagnosed with CDH by ICD-9 coding and gestational age <37 weeks. Descriptive statistics, chi-square, and trend analysis were completed.
We identified 2356 infants born prematurely with CDH. The overall survival rate was 49%. The survival range is 21.2-62.3% for gestational age <26 weeks to 35-36 weeks, respectively. Total mortality was 1183; of them, 1052 (89%) were not repaired and 363 (30.7%) did not receive mechanical ventilation. Surgical repair occurred in 55.1% of infants.
Preterm infants have lower survival compared with term infants. Survival rates decrease with lower gestational age and have improved over time.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
The prevalence, morbidity, and mortality associated with Ebstein anomaly (EA) remains poorly characterized in neonates. EA is a rare form of congenital heart disease (CHD) with significant ...heterogeneity.
Objective
To determine the recent, 2000–2018, prevalence, mortality, outcomes, and healthcare utilization of infants admitted at ≤28 days of life with EA in comparison to other critical congenital heart defects (CCHD) in the United States using a national data set.
Methods
The National Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP) was queried for infants admitted for any reason at ≤28 days of life with a diagnosis of EA between 2000 and 2018 using ICD‐9 and 10 codes in the United States. Patient characteristics, morbidity, mortality, and healthcare utilization were evaluated for EA and compared with other CCHD.
Results
From 2000 to 2018 a total of 68,312,952 neonatal admissions were identified, of them 4,398 neonates with isolated EA were identified, representing 7 per 100,000 neonatal admissions and 2.2% of CCHD admissions (4,398/197,881). The number of new EA cases ranged from 138 to 375 per year. In‐hospital mortality was 12.3% and surgical repair occurred in 4.2% for infants with EA. There were 470 deaths without surgical repair which is 86.6% of the mortality. Arrhythmias were diagnosed in 10.6% and ECMO was used for 2.6% of neonates with EA.
Conclusion
EA is a rare form of CHD. The prevalence has remained stable over the 19 years whereas other congenital heart defects have had an increase. The mortality in neonates with EA was significantly higher than in pooled CCHD; the burden of mortality occurred in the neonates without surgical intervention.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The clinical development of an inhibitor of cellular proteasome function suggests that compounds targeting other components of the ubiquitin-proteasome system might prove useful for the treatment of ...human malignancies. NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that controls the activity of the cullin-RING subtype of ubiquitin ligases, thereby regulating the turnover of a subset of proteins upstream of the proteasome. Substrates of cullin-RING ligases have important roles in cellular processes associated with cancer cell growth and survival pathways. Here we describe MLN4924, a potent and selective inhibitor of NAE. MLN4924 disrupts cullin-RING ligase-mediated protein turnover leading to apoptotic death in human tumour cells by a new mechanism of action, the deregulation of S-phase DNA synthesis. MLN4924 suppressed the growth of human tumour xenografts in mice at compound exposures that were well tolerated. Our data suggest that NAE inhibitors may hold promise for the treatment of cancer.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Post-acute sequelae of COVID-19 (PASC, “Long COVID”) pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several ...hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.
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•Long COVID is associated with reduced circulating serotonin levels•Serotonin depletion is driven by viral RNA-induced type I interferons (IFNs)•IFNs reduce serotonin through diminished tryptophan uptake and hypercoagulability•Peripheral serotonin deficiency impairs cognition via reduced vagal signaling
Post-viral syndromes are associated with serotonin reduction, which may contribute to the neurological and cognitive symptoms seen in individuals with Long COVID.
Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ ...FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a "bridging strategy" to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance.
Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis.
Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14-20), 472 cells/mm3 (IQR 384-651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2-4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms.
Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed.
Clinical Trials.gov NCT01338025.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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