As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass. On the first day of serum creatinine-defined AKI, we measured urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days). In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively. If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.
Background Inflammation is a key component of both acute kidney injury (AKI) and response to cardiopulmonary bypass. Since AKI poses risks to children after cardiac surgery, we investigated the value of inflammatory biomarkers interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF) for predicting AKI and other complications. Methods We enrolled 412 children between 1 month and 18 years old undergoing cardiopulmonary bypass for cardiac surgery. We collected blood both preoperatively and postoperatively (within 6 hours post-surgery) and measured plasma IL-8 and TNF. Results IL-8 and TNF did not predict AKI in children <2 years, but strongly associated with AKI in children ≥2 years. There were significant associations between biomarker levels and age (<2 or ≥2). In children ≥2, patients in the highest tertile of preoperative IL-8 and postoperative TNF had 4.9 [95% CI: 1.8–13.2]- and 3.3 [95% CI: 1.2–9.0]-fold higher odds of AKI compared to those in the lowest tertile. Children <2 with higher biomarker levels also had higher odds of AKI, but the difference was not significant. We also found that postoperative TNF levels were significantly higher in patients with longer hospital stays, and that both postoperative IL-8 and TNF levels were significantly higher in patients with longer ventilation lengths. However there was no evidence that biomarker levels mediated the association between AKI and length of ventilation; they appear to be independent predictors. Conclusions Preoperative IL-8 and postoperative TNF are significantly associated with higher odds of AKI and greater lengths of hospital stays and ventilator use in children ≥2.
Although intravenous racemic ketamine has rapid antidepressant properties, it is not approved for depression treatment. 1 However, the US Food and Drug Administration has approved intranasal esketamine for treatment-resistant depression. 1 Correia-Melo et al 2 treated 63 participants with intravenous ketamine or esketamine and observed that esketamine was noninferior to ketamine. A recent meta-analysis suggested that intravenous ketamine was more effective, 3 but the only head-to-head trial included was from Correia-Melo et al, 2 rendering interpretation difficult. To our knowledge, no multidose, head-to-head comparisons of these treatments have been reported.The Yale Interventional Psychiatry Service (IPS) provides both intravenous ketamine (0.5 mg/kg over 40 minutes) and intranasal esketamine (56 or 84 mg). Patients receive similar care with comparable protocols in the same physical space. We analyzed Yale IPS clinical data to evaluate these treatments in a clinical setting.Methods | For this comparative analysis, we reviewed retrospective data for all Yale IPS patients receiving intravenous ketamine or intranasal esketamine between September 2016 and April 2021 (eMethods in the Supplement). The Yale Institutional Review Board approved this analysis of existing clinical data and waived informed consent per the Common Rule. The analysis followed the ISPOR reporting guideline.Results | Of 210 included patients, 129 (61.4%) received intravenous ketamine and 81 (38.6%) received intranasal esketamine. There were no differences in baseline demographic factors (Table ). The estimated group difference in Montgomery-Åsberg Depression Rating Scale (MADRS) score by treatment end (primary outcome) was 2.15 (95% CI, −0.06 to 4.37; P = .06). Estimated group differences in Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores after full treatment course and MADRS and QIDS-SR scores after the first 6 treatments (secondary outcomes) were 1.59 (95% CI, 0.24-2.94; P = .02), 2.49 (95% CI, 0.01-4.98; P < .05), and 1.64 (0.08-3.19; P = .04), respectively, all favoring intravenous ketamine (Figure). Other models produced similar results. There were no group differences in response rates (37.8% [95% CI, 30.0%-46.3%] vs 36.0% [95% CI, 25.9%-47.5%]) or remission (29.6% [95% CI, 22.5%-37.9%] vs 24.0% [95% CI, 15.6%-35.0%]) for ketamine vs esketamine, respectively.
Analysis of California newborn screening (NBS) data revealed a high prevalence of Hispanic infants testing positive for methylmalonic acidemia (MMA), a trend seen for both true- and false-positive cases. Here we show that Hispanic infants have significantly higher levels of MMA screening markers than non-Hispanics. Preterm birth and increased birth weight were found to be associated with elevated MMA marker levels but could not entirely explain these differences. While the preterm birth rate was higher in Blacks than Hispanics, Black infants had on average the lowest MMA marker levels. Preterm birth was associated with lower birth weight and increased MMA marker levels suggesting that gestational age is the stronger predictive covariate compared to birth weight. These findings could help explain why MMA false-positive results are more likely in Hispanic than in Black infants, which could inform screening and diagnostic procedures for MMA and potentially other disorders in newborns.
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