Objective:To characterize gestational age (GA)-specific serum creatinine (SCr) trajectories among level IV neonatal intensive care unit (NICU) infants and develop an interactive interpretation tool. Study Design:We analyzed ADVANCE database records linking kidney-specific data with Children's Hospitals Neonatal Consortium clinical data from ten level IV NICUs (2010-2022). Infants with ≥ 1 SCr measurement (DOL 1-365) were included. GA-specific trajectories were generated for DOL 1-28 and week of life 1-16; an interactive tool was developed for clinical use. Result:Among 34,306 infants contributing 390,612 SCr measurements, SCr trajectories differed by GA. Peak SCr ranged from 0.93 mg/dL (IQR 0.80-1.10) at 22-24 weeks' GA (DOL 4) to 0.76 mg/dL (IQR 0.65-0.90) among term infants (DOL 2), declining to a similar nadir (~ 0.20-0.23 mg/dL) across GA groups. Conclusion:SCr trajectories vary by GA and postnatal age in this population. These trajectories and the accompanying tool provide context for interpreting SCr values.

Perinatal mood and anxiety disorders are common obstetric complications. Caregivers of infants in neonatal intensive care units and those visiting paediatric emergency departments experience a significantly higher risk of these disorders, with up to 45% screening positive for depressive symptoms in the neonatal intensive care unit and 27% in the paediatric emergency department. However, current screening and treatment systems in both settings are insufficient, with only a fraction of caregivers being screened. This study seeks to identify the drivers and barriers to effective screening for perinatal mood and anxiety disorders in both the neonatal intensive care unit and paediatric emergency department using a systems thinking approach called group model building. By engaging participants in mapping the factors influencing the screening system at the Children's National Hospital, this study identifies key mechanisms, including barriers and drivers, that affect screening performance. One barrier to increasing screening is the identification of positive cases, which demand staff attention and limit their ability to approach new caregivers. High staff turnover, driven by stress, low pay and the repetitive nature of the work, further limits the system's screening capacity. On the other hand, several factors can drive improvements in screening performance. A critical driver for enhancing screening is highlighting the prevalence of post-partum depression among caregivers and securing financial resources to support a dedicated team. This allows for greater diagnosis of affected caregivers and ensures sustainability and expansion of the programme. While efforts to reduce mental health stigma are slow to take effect, they can significantly improve screening rates over time. Additionally, optimizing waiting times in the paediatric emergency department can increase screening opportunities. The insights from this study may help improve existing screening programmes and guide other hospitals in initiating and sustaining similar efforts, ultimately benefiting both caregiver mental health and infant health outcomes in the neonatal intensive care unit and paediatric emergency department.

BACKGROUND:Acute kidney injury (AKI) occurs in up to half of infants admitted to the neonatal intensive care unit (NICU) and is associated with increased risks of death and more days of mechanical ventilation, hospitalization, and vasopressor drug support. Our objective was to build a granular relational database to study the impact that AKI has on infants admitted to Level-IV NICUs. METHODS:A relational database was created by linking data from the Children's Hospitals Neonatal Database with AKI-focused data from electronic health records from 9 centers. RESULTS:The current cohort consists of 24,870 infants with a median (IQR) gestational age of birth of 37 weeks (32 weeks, 39 weeks), and a median birth weight of 2.720 kg (1.750 kg, 3.310 kg). There was a male predominance with 14,214 (57%) males. In all, 2434 (9.8%) of the mothers were of Hispanic ethnicity. The maternal race breakdown of the cohort was as follows: 741 (3.0%) Asian, 5911 (24%) Black, and 14,945 (60%) White. Overall mortality was 5.8%. CONCLUSION:The ADVANCE relational database is an innovative research tool to rigorously study the epidemiology of AKI in a large national cohort of infants admitted to Level-IV NICUs involved in the Children's Hospital Neonatal Consortium. IMPACT:We used a biomedical informatics approach to build a relational database to study acute kidney injury in infants. We highlight our methodology linking Children's Hospital Neonatal Consortium and electronic health record data from nine neonatal intensive care units. The ADVANCE relational database is a granular and innovative research tool to study risk factors and in-hospital outcomes of acute kidney injury and mortality in a vulnerable patient population.

Parental mental health is an essential sixth vital sign that, when taken into consideration, allows clinicians to improve clinical outcomes for both parents and infants. Although standards exist for screening, referral, and treatment for perinatal mood and anxiety disorders (PMADs), they are not reliably done in practice, and even when addressed, interventions are often minimal in scope. Quality improvement methodology can accelerate the implementation of interventions to address PMADs, but hurdles exist, and systems are not well designed, particularly in pediatric inpatient facilities. In this article, we review the effect of PMADs on parents and their infants and identify quality improvement interventions that can increase screening and referral to treatment of parents experiencing PMADs.

Abstract Pediatric chronic critical illness (PCCI) is characterized by prolonged and recurrent hospitalizations, multiorgan conditions, and use of medical technology. Our prior work explored the mismatch between intensive care unit (ICU) acute care models and the chronic needs of patients with PCCI. The objective of this study was to examine whether the number and frequency of treatment weans in ICU care were associated with clinical setbacks and/or length of stay for patients with PCCI. A retrospective chart review of the electronic medical record for 300 pediatric patients with PCCI was performed at the neonatal intensive care unit, pediatric intensive care unit, and cardiac intensive care unit of two urban children's hospitals. Daily patient care data related to weans and setbacks were collected for each ICU day. Data were analyzed using multilevel mixed multiple logistic regression analysis and a multilevel mixed Poisson regression. The patient-week level adjusted regression analysis revealed a strong correlation between weans and setbacks: three or more weekly weans yielded an odds ratio of 3.35 (95% confidence interval [CI] = 2.06–5.44) of having one or more weekly setback. There was also a correlation between weans and length of stay, three or more weekly weans were associated with an incidence rate ratio of 1.09 (95% CI = 1.06–1.12). Long-stay pediatric ICU patients had more clinical setbacks and longer hospitalizations if they had more than two treatment weans per week. This suggests that patients with PCCI may benefit from a slower pace of care than is traditionally used in the ICU. Future research to explore the causative nature of the correlation is needed to improve the care of such challenging patients.

Background:Neonates exposed to painful procedures require pain assessment and reassessment using nonverbal scales. Nurses perform initial assessments routinely, but reassessment is variable. The goal was to increase pain reassessments in neonates with a previous score of 4 or higher within 60 minutes from 50% to 75% within 12 months.Methods:After identifying key drivers, we tested several interventions using the IHI's Model for Improvement. The outcome measure was the rate of reassessments within 1 hour after scoring ≥4 on the Neonatal Pain Agitation and Sedation Scale (N-PASS). Duration of time between scoring and intervention was documented. Interventions included electronic health record (EHR) changes, direct communication with bedside nurses through text messages and emails, in-person education, and a yearly competency module. The process measure was the number of messages/emails to staff. Sedation scores were the balancing measure.Results:Baseline compliance was 50% with significant variability. A centerline shift occurred after the first intervention. After the first four interventions in the following 3 months, a 29% total increase occurred. Overall time-lapse between reassessments decreased from 102 to 90 minutes. Overall sedation scores decreased from -2.5 during the baseline to -1.7 during the sustain period. The goal of 75% pain reassessments was achieved and sustained for two years.Conclusions:Automated tools such as the trigger report provided data that increased noncompliance visibility. Real-time and personalized reminders and education improved awareness and set the tone for culture change. Electronic health record reminders for reassessments and standardized annual education helped in sustaining change.

INTRODUCTION:Previous studies in term newborns with hypoxic ischemic encephalopathy showed that the rate of serum creatinine (SCr) decline during the first week of life could be used to identify newborns with impaired kidney function (IKF) who are missed by standard definitions of neonatal acute kidney injury (nAKI).METHODS:Retrospective review of the medical records of 329 critically ill newborns ≥27 weeks of gestational age (GA) admitted to a level 4 neonatal intensive care unit (NICU). We tested the hypothesis that the rate of SCr decline combined with SCr thresholds provides a sensitive approach to identify term and preterm newborns with IKF during the first week of life.RESULTS:Excluding neonates with nAKI, an SCr decline <31% by the seventh day of life, combined with an SCr threshold ≥0.7 mg/dl, recognized newborns of 40 to 31 weeks of GA with IKF. An SCr decline <21% combined with an SCr threshold ≥0.8 mg/dl identified newborns of 30 to 27 weeks of GA with IKF. Neonates with IKF (∼17%), like those with nAKI (7%), showed a more prolonged hospital stay and required more days of mechanical ventilation, vasoactive drugs, and diuretics, when compared with the controls. Changes in urine output did not distinguish newborns with IKF.CONCLUSION:The rate of SCr decline combined with SCr thresholds identifies newborns with IKF during the first week of life. This distinctive group of newborns that is missed by standard definitions of nAKI, warrants close monitoring in the NICU to prevent further renal complications.

Objective This study aimed to evaluate the association between acute kidney injury (AKI) and lung outcomes in infants born >= 32 weeks of gestational age (GA). Study Design Secondary analysis of infants >= 32 weeks of GA in the assessment of worldwide acute kidney injury epidemiology in neonates (AWAKEN) retrospective cohort ( n = 1,348). We used logistic regression to assess association between AKI and a composite outcome of chronic lung disease (CLD) or death at 28 days of age and linear regression to evaluate association between AKI and duration of respiratory support. Results CLD occurred in 82/1,348 (6.1%) infants, while death occurred in 22/1,348 (1.6%); the composite of CLD/death occurred in 104/1,348 (7.7%). Infants with AKI had an almost five-fold increased odds of CLD/death, which remained after controlling for GA, maternal polyhydramnios, multiple gestations, 5-minute Apgar's score, intubation, and hypoxic-ischemic encephalopathy (adjusted odds ratio [OR] = 4.9, 95% confidence interval [CI]: 3.2-7.4; p < 0.0001). Infants with AKI required longer duration of respiratory support (count ratio = 1.59, 95% CI: 1.14-2.23, p = 0.003) and oxygen (count ratio = 1.43, 95% CI: 1.22-1.68, p < 0.0001) compared with those without AKI. Conclusion AKI is associated with CLD/death and longer duration of respiratory support in infants born at >= 32 weeks of GA. Further prospective studies are needed to elucidate the pathophysiologic relationship.

Neonates with serum creatinine (SCr) rise ≥0.3 mg/dL and/or ≥50% SCr rise are more likely to die, even when controlling for confounders. These thresholds have not been tested in newborns. We hypothesized that different gestational age (GA) groups require different SCr thresholds. Neonates in Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) with ≥1 SCr on postnatal days 1–2 and ≥1 SCr on postnatal days 3–8 were assessed. We compared the mortality predictability of SCr absolute (≥0.3 mg/dL) vs percent (≥50%) rise. Next, we determine usefulness of combining absolute with percent rise. Finally, we determined the optimal absolute, percent, and maximum SCr thresholds that provide the highest mortality area under curve (AUC) and specificity for different GA groups. The ≥0.3 mg/dL rise outperformed ≥50% SCr rise. Addition of percent rise did not improve mortality predictability. The optimal SCr thresholds to predict AUC and specificity were ≥0.3 and ≥0.6 mg/dL for ≤29 weeks GA, and ≥0.1 and ≥0.3 mg/dL for >29 week GA. The maximum SCr value provides great specificity. Unique SCr rise cutoffs for different GA improves outcome prediction. Percent SCr rise does not add value to the neonatal AKI definition.

A significant number of children infected with the human immunodeficiency virus 1 (HIV-1) virus all over the world are at risk of developing renal diseases that could have a significant impact on their treatment and quality of life. It is necessary to identify children undergoing the early stages of these renal diseases, as well as the potential renal toxicity that could be caused by antiretroviral drugs, in order to prevent the development of cardiovascular complications and chronic renal failure. This article describes the most common renal diseases seen in HIV-infected children, as well as the value and limitations of the clinical markers that are currently being used to monitor their renal function and histological damage in a noninvasive manner. In addition, we discuss the progress made during the last 10 years in the discovery and validation of new renal biomarkers for HIV-infected children and young adults. Although significant progress has been made during the early phases of the biomarkers discovery, more work remains to be done to validate the new biomarkers in a large number of patients. The future looks promising, however, the new knowledge needs to be integrated and validated in the context of the clinical environment where these children are living.

Capillary zone electrophoresis on-line coupled to mass spectrometry: A perspective application for clinical proteomics Martin Pejchinovski, Dajana Hrnjez, Adela Ramirez-Torres, Vasiliki Bitsika, George Mermelekas, Antonia Vlahou, Petra Zürbig, Harald Mischak, Jochen Metzger and Thomas Koeck Proteomics Clin. Appl. 2015, 9, 453–468. DOI: 10.1002/prca.201400113 State-of-the-art nanoplatform-integrated MALDI-MS impacting resolutions in urinary proteomics Judy Gopal, Manikandan Muthu, SeChul Chun and Hui-Fen Wu Proteomics Clin. Appl. 2015, 9, 469–481. DOI: 10.1002/prca.201400182

Acute kidney injury (AKI) increases the morbidity of critically ill children. Thus, it is necessary to identify better renal biomarkers to follow the outcome of these patients. This prospective case–control study explored the clinical value of a urinary biomarker profile comprised of neutrophil gelatinase lipocalin (uNGAL), fibroblast growth factor-2 (uFGF-2), and epidermal growth factor (uEGF) to follow these patients.

The goal of this study was to assess the value of a urinary biomarker profile comprised of neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n = 10). Urine was collected at baseline, 48 h of illness, and > 24 h post-recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 h and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50 % post-recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. Fifteen at-risk newborns had AKI. In the first 48 h of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74 % and specificity of 84 %. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery identified critically ill neonates with AKI. These findings require validation in larger prospective studies.

Fibroblast growth factor-2 (FGF-2) is an angiogenic growth factor involved in renal growth and regeneration. Previous studies in rodents revealed that single intrarenal injections of FGF-2 improved the outcome of acute kidney injury (AKI). Septic children usually show elevated plasma levels of FGF-2, and are at risk of developing AKI. However, the role of circulating FGF-2 in the pathogenesis of AKI is not well understood. We have developed a mouse model to determine how FGF-2 released into the circulation modulates the outcome of AKI induced by lipopolysaccharide (LPS). Young FVB/N mice were infected with adenoviruses carrying a secreted form of human FGF-2 or control LacZ vectors. Subsequently, when the circulating levels of FGF-2 were similar to those seen in septic children, mice were injected with a non-lethal dose of LPS or control buffer. All mice injected with LPS developed hypotension and AKI, from which they recovered after 5 days. FGF-2 did not improve the outcome of AKI, and induced more significant renal proliferative and apoptotic changes during the recovery phase. These findings suggest that circulating FGF-2 may not necessarily prevent the development or improve the outcome of AKI. Moreover, the renal accumulation of FGF-2 might cause further renal damage.

1. Novel Biomarkers of Stroke Progression Identified by Temporal Quantitative Proteomic Screening MingMing Ning, Mary Lopez, Dave Sarracino, Michael Athenas, David McMullin, Ferdinando S. Buonanno, Eng H. Lo Neurology, Mass Gen Hosp/Harvard Med School, Boston, MA, United States. 2. Speckle Tracking-Derived Diastolic Function Predicts Mortality in Patients with Acute Coronary Syndrome Sirikarn Napan, Thaslim Kassim, Bryan Curry, Michael Greenberg Howard University, Washington, DC, United States. 3. The Effect of Race on All-Cause Mortality After Cardiac Surgery: A Single Institutional Experience in a Veteran Population Over 20 Years Isaac Opoku-Asare, Thaslim Kassim, Rebecca Chornock, Jason Morrissette, Erin Goheen, Peter Kokkinos, Micheal D. Greenberg, Gregory Trachiotis Cardiovascular Medicine, Howard University Hospital, Washington, DC, United States; Cardiothoracic Surgery, Veteran Medical Center, Washington, DC, United States; Cardiology, Veteran Medical Center, Washington, DC, United States; Internal Medicine, Howard University Hospital, Washington, DC, United States. 4. Olfactory Phenotyping in Isolated Gonadotropin Releasing Hormone Deficiency: A Systematic Analysis Hilana M. Lewkowitz-Shpuntoff, Ravikumar Balasubramanian, Virginia Hughes, Margaret Au, William F. Crowley Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, United States. 5. Outcomes and Survival With Aortic Valve Replacement Compared With Medical Therapy in Patients With Low-, Moderate-, and Severe-Gradient Severe Aortic Stenosis and Normal Left Ventricular Ejection Fraction Mala Sharma, Omar Khalique, Wilbert S. Aronow, Robert N. Belkin, Chul Ahn Cardiology, Westchester Medical Center of New York Medical College, Valhalla, NY, United States; University of Texas Southwestern Medical Center, Dallas, TX, United States.