The purpose of this Neonatal and Pediatric Heart and Renal Outcomes Network study was to describe the epidemiology and outcomes of cardiac surgery–associated acute kidney injury (CS-AKI) after ...cardiac surgery without cardiopulmonary bypass (non-CPB).
We performed a retrospective study of neonates (≤30 days) who underwent non-CPB cardiac surgery at 22 centers affiliated with the Pediatric Cardiac Critical Care Consortium. CS-AKI was defined using the modified Kidney Disease: Improving Global Outcomes serum creatinine and urine output criteria from postoperative days 0 to 6. CS-AKI defined by serum creatinine was further subclassified into transient (resolved by postoperative day 3) and persistent/late (≥3 days). Multivariable regression analyses were used to determine risk factors for CS-AKI and associations with outcomes of ventilation hours and cardiac intensive care unit length of stay.
Five hundred eighty-two neonates (median age at surgery, 9 days interquartile range, 5-15, 25% functional single ventricle were included. CS-AKI occurred in 38.3%: Rate and severity varied across centers. Aggregate daily CS-AKI prevalence peaked on postoperative day 1 (17.1%). No stage of CS-AKI was associated with ventilation hours or length of stay. Persistent/late CS-AKI occurred in 48 patients (8%). Prostaglandin use and single-ventricle surgery were associated with persistent/late CS-AKI. Higher baseline serum creatinine but not persistent/late CS-AKI was associated with longer ventilation duration and intensive care unit length of stay after adjusting for confounders.
Kidney Disease: Improving Global Outcomes–defined CS-AKI occurred commonly in neonates undergoing non-CPB cardiac surgery. However most CS-AKI was transient, and no CS-AKI classification was associated with worse outcomes. Further work is needed to determine the CS-AKI definition that best associates with outcomes in this cohort.
There is increasing evidence of the clinical utility of genetic and genomic testing (GT); however, factors influencing personal utility of GT, especially in diverse, multilingual populations, remain ...unclear. We explored these factors in a diverse cohort of parents/guardians (participants) whose children received clinical GT through the NYCKidSeq program. A total of 847 participants completed surveys at baseline, post-results disclosure, and 6 months (6m) post-results. The largest population groups were Hispanic/Latino(a) (48%), White/European American (24%), and Black/African American (16%). Personal utility was assessed using the Personal Utility (PrU) scale, adapted for pediatric populations and included on the surveys. Three PrU subscales were identified using factor analysis: practical, educational, and parental psychological utility. Overall personal utility summary score and the three subscales significantly decreased after receiving results and over time. Hispanic/Latino(a) participants identified greater overall personal utility than European American and African American participants at all time points (p < 0.001) as did participants whose children received positive/likely positive results compared with those with negative and uncertain results (post-results: p < 0.001 and p < 0.001; 6m post-results: p = 0.002 and p < 0.001, respectively). Post-results, higher utility subscale scores were associated with lower education levels (practical, parental psychological: p ≤ 0.02) and higher levels of trust in the healthcare system (practical, parental psychological: p ≤ 0.04). These findings help to understand the perspectives of diverse parents/guardians, which is critical to tailoring pre- and post-test counseling across a variety of populations and clinical settings.
This study evaluated personal utility of pediatric genomic testing among a diverse cohort, identifying three domains: practical, educational, and parental psychological. Personal utility decreased over time. Sociodemographic factors including education, health literacy, and healthcare distrust significantly influenced personal utility. Understanding these factors is crucial for tailored counseling across diverse populations.
Objective
To evaluate salivary progesterone as a predictor of early preterm birth (PTB) and compare it with transvaginal sonographic (TVS) cervical length in asymptomatic high‐risk women.
Design
...Prospective study.
Setting
Departments of Obstetrics and Gynaecology and Biochemistry at UCMS & GTBH, Delhi, India.
Sample
Ninety pregnant women.
Methods
The progesterone concentration in saliva of asymptomatic pregnant women at high risk for preterm delivery was estimated by immunoassay, and cervical length was measured by TVS, at the first antenatal visit at 24–28 weeks of gestation, and then repeated 3–4 weeks later.
Main outcome measures
Early PTB, mean and critical cut‐off values of salivary progesterone, and a diagnostic value comparison of salivary progesterone with TVS cervical length.
Results
The mean value of salivary progesterone was significantly lower in all women who delivered at <37 weeks of gestation (n = 38), compared with the term group (n = 52; P < 0.001). Salivary progesterone decreased significantly from the first to the second visit, with the maximum decrease observed in women who delivered at <34 weeks of gestation (29.6%, 95% CI 17.8–41.4%, P < 0.002). The single predictive critical cut‐off value for salivary progesterone was 2575 pg/ml, below which more than 80% of women delivered prematurely before 34 weeks of gestation, with sensitivity, specificity, and positive and negative predictive values of 83% (95% CI 58.6–96.4%), 86% (95% CI 75.9–93.1%), 60% (95% CI 38.6–78.8%) and 95% (95% CI 87.1–99.0%), respectively. The TVS cervical length decreased significantly (P < 0.001) in the women who delivered prematurely.
Conclusions
Low salivary progesterone concentration can be used for predicting early PTB in asymptomatic high‐risk women.
Viral infections of the central nervous system (CNS) often cause disease in an age‐dependent manner, with greater neuropathology during the fetal and neonatal periods. Transgenic CD46+ mice model ...these age‐dependent outcomes through a measles virus infection of CNS neurons. Adult CD46+ mice control viral spread and survive the infection in an interferon gamma (IFNγ)‐dependent manner, whereas neonatal CD46+ mice succumb despite similar IFNγ expression in the brain. Thus, we hypothesized that IFNγ signaling in the adult brain may be more robust, potentially due to greater basal expression of IFNγ signaling proteins. To test this hypothesis, we evaluated the expression of canonical IFNγ signaling proteins in the neonatal and adult brain, including the IFNγ receptor, Janus kinase (JAK) 1/2, and signal transducer and activator of transcription‐1 (STAT1) in the absence of infection. We also analyzed the expression and activation of STAT1 and IFNγ‐stimulated genes during MV infection. We found that neonatal brains have equivalent or greater JAK/STAT1 expression in the hippocampus and the cerebellum than adults. IFNγ receptor expression varied by cell type in the brain but was widely expressed on neuronal and glial cells. During MV infection, increased STAT1 expression and activation correlated with viral load in the hippocampus regardless of age, but not in the cerebellum where viral load was consistently undetectable in adults. These results suggest the neonatal brain is capable of initiating IFNγ signaling during a viral infection, but that downstream STAT1 activation is insufficient to limit viral spread.
Nonalcoholic fatty liver disease (NAFLD) is becoming the most common indication for liver transplantation. The growing prevalence of NAFLD not only increases the demand for liver transplantation, but ...it also limits the supply of available organs because steatosis predisposes grafts to ischemia/reperfusion injury (IRI) and many steatotic grafts are discarded. We have shown that monoacylglycerol acyltransferase (MGAT) 1, an enzyme that converts monoacylglycerol to diacylglycerol, is highly induced in animal models and patients with NAFLD and is an important mediator in NAFLD‐related insulin resistance. Herein, we sought to determine whether Mogat1 (the gene encoding MGAT1) knockdown in mice with hepatic steatosis would reduce liver injury and improve liver regeneration following experimental IRI. Antisense oligonucleotides (ASO) were used to knockdown the expression of Mogat1 in a mouse model of NAFLD. Mice then underwent surgery to induce IRI. We found that Mogat1 knockdown reduced hepatic triacylglycerol accumulation, but it unexpectedly exacerbated liver injury and mortality following experimental ischemia/reperfusion surgery in mice on a high‐fat diet. The increased liver injury was associated with robust effects on the hepatic transcriptome following IRI including enhanced expression of proinflammatory cytokines and chemokines and suppression of enzymes involved in intermediary metabolism. These transcriptional changes were accompanied by increased signs of oxidative stress and an impaired regenerative response. We have shown that Mogat1 knockdown in a mouse model of NAFLD exacerbates IRI and inflammation and prolongs injury resolution, suggesting that Mogat1 may be necessary for liver regeneration following IRI and that targeting this metabolic enzyme will not be an effective treatment to reduce steatosis‐associated graft dysfunction or failure.
Background. The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5—vectored vaccine ...designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial. Methods. Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5 human immunodeficiency virus type 1 vaccine containing from 3×106 to 1×1011 viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-γ enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose. Results. Of 259 randomized individuals, 257 (99%) received ⩾1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of ⩾3×109 viral particles elicited positive enzyme-linked immunosorbent spot responses to ⩾1 vaccine component in >60% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzyme-linked immunosorbent spot responses at all doses except the 3×1010 viral particle dose. Conclusions. The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy.
Abstract BACKGROUND Children and young adults diagnosed with high-grade glioma (HGG) face extremely poor prognoses. Despite multiple clinical trials testing new treatments in this population, a ...survival advantage has yet to be achieved. Herein we assessed, in a single-arm, multi-center pilot trial, the feasibility of molecular profiling of primary HGG tumor tissue to create an individualized treatment plan with up to four FDA approved medications. METHODS Patients aged <21 years with newly diagnosed, localized, hemispheric HGG (Stratum A) or midline HGG (non-DIPG; Stratum B) were eligible. Tumor tissue underwent comprehensive molecular profiling (targeted gene panel, whole exome, and whole transcriptome sequencing). Based on detailed review of the molecular data by a dedicated tumor board, an individualized treatment plan that combined up to four FDA approved drugs was recommended. Circulating tumor DNA (ctDNA), imaging, and quality of life (QOL) measures were collected at multiple timepoints. RESULTS Fifty-five patients enrolled between 2018 and 2023 (median age 11 years range 2-20, n=31 female, n=29 Stratum A). The most common integrated diagnoses included H3K27-altered diffuse midline glioma (n=17), H3/IDH-wildtype diffuse pediatric-type HGG (n=16), and H3G34-mutant diffuse hemispheric glioma (n=12). Median overall survival (OS) from the time of study enrollment was 26.5 months in Stratum A (lower 95% CI: 18.7) and 21.7 months in Stratum B (lower 95% CI: 16.8), with a median follow-up of 35.4 months for all patients (lower 95% CI: 32.5). The most common grade 3 or 4 treatment-related adverse events were decreased neutrophils (n=28), decreased platelets (n=22), and decreased white blood cells (n=16). As of December 2023, seven patients remain on therapy. Central imaging, ctDNA, and QOL analyses are underway. CONCLUSIONS A personalized treatment recommendation for children and young adults with HGG based on comprehensive transcriptomic and genomic analysis is feasible. Current survival data are encouraging, and molecular subgroup analyses are ongoing.
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•The nonlinear optical properties of LDS 821 in different solvents were investigated.•The nonlinear optical properties of LDS 821 dye were predicted theoretically.•Linear and ...nonlinear optical properties of LDS 821 dye in DNA was investigated.•The influence of dihedral angle on nonlinear optical properties of LDS 821 dye on DNA was studied.
Linear and nonlinear optical properties of near-infrared laser grade dye LDS 821 in different solvents and Salmon Deoxyribonucleic acid (DNA) were studied using spectroscopic and Z-scan techniques. UV–Vis absorption spectrum of the dye shows a bathochromic shift with a decrease in the solvent polarity parameter, and in DNA, the dye exhibits a hypochromic shift. The fluorescence spectrum of the dye does not show any notable correlation with the solvent polarity parameter, but in DNA, the fluorescence intensity of the dye decreases with the incremental addition of DNA. Molecular docking studies reveal that the dye intercalates on the major grooves of DNA. Nonlinear optical properties of the dye in different solvents and phosphate buffer solution with varying DNA concentrations were studied using the Z-scan technique using a Q-switched Nd: YAG laser operating at fundamental and second harmonics. A closed and open aperture Z-scan of dye in different solvents was carried out to estimate the nonlinear refractive index, excited-state absorption cross-section, and two-photon absorption coefficient (TPA). The variation in nonlinear optical properties of the dye in different solvents was due to solvent-induced structural modifications. Theoretical investigation on nonlinear optical properties of the dye in different solvents was carried out using density function theory. The theoretical first and second-order hyperpolarizability was calculated using B3LYP functional. The predicated nonlinear optical parameters of the dye in different solvents does not show any direct correlation with solvent polarity. Nonlinear absorption of the dye in phosphate buffer solution (PBS) and DNA were estimated. The nonlinear absorption of the dye in PBS decreases with the addition of DNA. Molecular docking studies were carried out to determine the structural changes induced in dye due to the intercalation with DNA.
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