Clearance and nutrition in neonatal continuous kidney replacement therapy using the Carpediem™ system.

BACKGROUND: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). METHODS: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal-Wallis analysis were performed using SAS version 9.4. RESULTS: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). CONCLUSIONS: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein.

Nutritional Considerations for the Neonate With Congenital Heart Disease.

The importance of nutrition in managing critically ill infants with congenital heart disease (CHD) is foundational to optimizing short- and long-term health outcomes. Growth failure and malnutrition are common in infants with CHD. The etiology of growth failure in this population is often multifactorial and may be related to altered metabolic demands, compromised blood flow to the intestine leading to nutrient malabsorption, cellular hypoxia, inadequate energy intake, and poor oral-motor skills. A dearth of high-quality studies and gaps in previously published guidelines have led to wide variability in nutrition practices that are locally driven. This review provides recommendations from the nutrition subgroup of the Neonatal Cardiac Care Collaborative for best evidence-based practices in the provision of nutritional support in infants with CHD. The review of evidence and recommendations focused on 6 predefined areas of clinical care for a target population of infants <6 months with CHD admitted to the ICU or inpatient ward. These areas include energy needs, nutrient requirements, enteral nutrition, feeding practice, parenteral nutrition, and outcomes. Future progress will be directed at quality improvement efforts to optimize perioperative nutrition management with an increasing emphasis on individualized care based on nutritional status, cardiorespiratory physiology, state of illness, and other vulnerabilities.

Training pathways and careers for neonatologists interested in cardiovascular care.

Neonatologists and neonatal-perinatal trainees continue to be invested in the cardiovascular care of the newborn, many focusing their careers in this area of expertise. Multiple formalized structured and non-structured training pathways have evolved for neonatologists caring for infants with congenital heart disease and other cardiovascular pathologies. Furthermore, the evolution of neonatal hemodynamic science over the past decade has also spawned a formal training pathway in hemodynamics consultation to enhance standard of care and guide the management of infants at risk for cardiovascular compromise. Neonatologists have also chosen to expand upon on their neonatology training with clinical and research exposure to enhance their roles in neonatal cardiovascular care, including fetal care consultation, delivery room management, and perioperative cardiac intensive care consultation. To provide insight and career guidance to interested neonatal trainees and early career physicians, this perspective article highlights several different pathways in the care of neonates with cardiovascular disease.

A preoperative standardized feeding protocol improves human milk use in infants with complex congenital heart disease.

OBJECTIVE: To evaluate the hypothesis that implementation of a preoperative standardized feeding protocol increases human milk use in infants with complex congenital heart disease (CHD). STUDY DESIGN: Single-center, quasi-experimental study of infants with complex CHD. A cohort of 546 infants pre protocol was compared to 55 patients post protocol. Feeding regimen and peri-operative outcomes information were collected. RESULT: Human milk use increased significantly (58.4% versus 100%, p < 0.01) and there was no formula use post protocol (18.7% versus 0%, p < 0.01). Preoperative necrotizing enterocolitis occurred in 18/546 (3.3%) infants pre protocol versus 1/55 (1.8%) post protocol, p = 1.00. Days to full feeds and length of hospital stay in both cohorts were not significantly different. CONCLUSION: Successful implementation of a preoperative standardized feeding protocol can increase human milk and decrease formula use in infants with complex CHD without significant adverse outcomes. A larger study is needed to evaluate the association of human milk use with peri-operative outcomes.

The Relationship Between Preoperative Feeding Exposures and Postoperative Outcomes in Infants With Congenital Heart Disease.

OBJECTIVES: To evaluate the association of preoperative risk factors and postoperative outcomes in infants with complex congenital heart disease. DESIGN: Single-center retrospective cohort study. SETTING: Neonatal ICU and cardiovascular ICU. PATIENTS: Infants of all gestational ages, born at Texas Children's Hospital between 2010 and 2016, with complex congenital heart disease requiring intervention prior to discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 399 patients were enrolled in the study. Preoperative risk factors included feeding, type of feeding, feeding route, and cardiac lesion. Postoperative outcomes included necrotizing enterocolitis, hospital length of stay, and days to full feeds. The occurrence rate of postoperative necrotizing enterocolitis (all stages) was 8%. Preoperative feeding, type of feeding, feeding route, and cardiac lesion were not associated with higher odds of postoperative necrotizing enterocolitis. Cardiac lesions with ductal-dependent systemic blood flow were associated with a hospital length of stay of 19.6 days longer than those with ductal-dependent pulmonary blood flow (p < 0.001) and 2.9 days longer to reach full feeds than those with ductal-dependent pulmonary blood flow (p < 0.001), after controlling for prematurity. Nasogastric feeding route preoperatively was associated with a length of stay of 29.8 days longer than those fed by mouth (p < 0.001) and 2.4 days longer to achieve full feeds (p < 0.001), after controlling for prematurity and cardiac lesion. Preoperative diet itself was not associated with significant change in length of stay or days to reach full feeds. CONCLUSIONS: Although cardiac lesions with ductal-dependent systemic blood flow are considered high risk and may increase length of stay and days to achieve full feeds, they are not associated with a higher risk of postoperative necrotizing enterocolitis. Nasogastric route is not associated with a significantly higher risk of necrotizing enterocolitis, but longer length of stay and days to reach full feeds. These findings challenge our perioperative management strategies in caring for these infants, as they may incur more hospital costs and resources without significant medical benefit.

Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.

OBJECTIVE: In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes. METHODS: In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type. RESULTS: Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise. CONCLUSIONS: Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.

Preoperative Feeds in Ductal-Dependent Cardiac Disease: A Systematic Review and Meta-analysis.

CONTEXT: Our aim for this review is to determine if preoperative feeds in neonates with ductal-dependent congenital heart disease are harmful or beneficial. OBJECTIVES: To summarize current evidence for preoperative feeding in neonates with ductal-dependent congenital heart disease. DATA SOURCES: We used the following databases: Medline, Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: We included observational studies in which the following outcomes were addressed: necrotizing enterocolitis (NEC), hospital length of stay (LOS), time to achieve full postoperative enteral feeding, and feeding intolerance. DATA EXTRACTION: Two reviewers independently screened each study for eligibility and extracted data. Methodologic quality was assessed by using a standardized item bank, and certainty of evidence for each outcome was assessed by using Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: Five retrospective cohort studies were eligible for inclusion, for which risk of bias was significant. When comparing neonates who received preoperative feeds with those who did not, there was no significant difference in NEC (pooled odds ratio = 1.09 [95% confidence interval 0.06-21.00; P = .95]; 3 studies, 6807 participants, very low certainty evidence), hospital LOS (mean of 14 days for those not fed versus 9.9 days for those fed preoperatively; P < .01; 1 study, 57 participants, very low certainty evidence), or feeding intolerance (odds ratio = 2.014 [95% confidence interval 0.079-51.703; P = .67]; 1 study, 56 participants, very low certainty evidence). No data were available for the outcome time to achieve full postoperative enteral feeding. All studies were observational and had small sample sizes. CONCLUSIONS: There is insufficient evidence to suggest that preoperative enteral feeds in patients with ductal-dependent cardiac lesions adversely influence the rate of NEC, LOS, or feeding intolerance.

Fibrin as a Tissue Adhesive and Scaffold with an Angiogenic Agent (FGF-1) to Enhance Burn Graft Healing In Vivo and Clinically.

There is a need for a strategy to reduce scarring in meshed skin graft healing leading to a better cosmetic result without a significant increase in cost. The strategy in this paper is to increase the closure rate of a meshed skin graft to reduce scarring, which should also decrease the infection rate. Specifically, we used fibrin glue to attach all parts of the graft to the wound bed and added in an angiogenic growth factor and made the fibrin porous to further help the growth of blood vessels from the wound bed into the graft. There was a 10-day animal study and a one-month clinical study. Neither making the fibrin porous or adding an angiogenic agent (i.e., fibroblast growth factor-1 (FGF-1)) seemed to make a significant improvement in vivo or clinically. The use of fibrin on a meshed skin graft appears to speed up the regenerative healing rate leading to less scarring in the holes in the mesh. It appears to shorten the healing time by five days and keep the tissue stiffness close to normal levels vs. the doubling of the stiffness by the controls. A larger clinical study, however, is needed to definitively prove this benefit as well as the mechanism for this improvement.

Successful Management of Neobladder Variceal Bleeding.

Hematuria from a neobladder can occur due to a variety of pathologies including tumors, stones, and fistulas. Variceal bleeding in a neobladder is a very rare condition with only one case reported in literature. We present a case of a patient with cirrhosis and portal hypertension and an ileocolic orthotopic neobladder presenting with hematuria. Computed tomographic angiography showed dilated varices around the neobladder which were successfully embolized. To the best of our knowledge, this is the first report case of variceal bleeding in a neobladder successfully managed with the combination of TIPS (transjugular intrahepatic portosystemic shunt) procedure and embolization.

Sirtuin 3 deficiency does not augment hypoxia-induced pulmonary hypertension.

Alveolar hypoxia elicits increases in mitochondrial reactive oxygen species (ROS) signaling in pulmonary arterial (PA) smooth muscle cells (PASMCs), triggering hypoxic pulmonary vasoconstriction. Mice deficient in sirtuin (Sirt) 3, a nicotinamide adenine dinucleotide-dependent mitochondrial deacetylase, demonstrate enhanced left ventricular hypertrophy after aortic banding, whereas cells from these mice reportedly exhibit augmented hypoxia-induced ROS signaling and hypoxia-inducible factor (HIF)-1 activation. We therefore tested whether deletion of Sirt3 would augment hypoxia-induced ROS signaling in PASMCs, thereby exacerbating the development of pulmonary hypertension (PH) and right ventricular hypertrophy. In PASMCs from Sirt3 knockout (Sirt3(-/-)) mice in the C57BL/6 background, we observed that acute hypoxia (1.5% O2; 30 min)-induced changes in ROS signaling, detected using targeted redox-sensitive, ratiometric fluorescent protein sensors (roGFP) in the mitochondrial matrix, intermembrane space, and the cytosol, were indistinguishable from Sirt3(+/+) cells. Acute hypoxia-induced cytosolic calcium signaling in Sirt3(-/-) PASMCs was also indistinguishable from Sirt3(+/+) cells. During sustained hypoxia (1.5% O2; 16 h), Sirt3 deletion augmented mitochondrial matrix oxidant stress, but this did not correspond to an augmentation of intermembrane space or cytosolic oxidant signaling. Sirt3 deletion did not affect HIF-1α stabilization under normoxia, nor did it augment HIF-1α stabilization during sustained hypoxia (1.5% O2; 4 h). Sirt3(-/-) mice housed in chronic hypoxia (10% O2; 30 d) developed PH, PA wall remodeling, and right ventricular hypertrophy that was indistinguishable from Sirt3(+/+) littermates. Thus, Sirt3 deletion does not augment hypoxia-induced ROS signaling or its consequences in the cytosol of PASMCs, or the development of PH. These findings suggest that Sirt3 responses may be cell type specific, or restricted to certain genetic backgrounds.

Size-selective synthesis of immobilized copper oxide nanoclusters on silica.

We report a straightforward route for preparing bulk quantities of size-controlled and low size dispersity copper oxide nanoclusters on amorphous silica. Adsorption of the copper-dendrimer complex on the silica surface minimizes aggregation, which results in previously unachieved low size dispersity of the nanoclusters. Copper oxide nanoclusters with mean diameters of 1-5 nm with size dispersities of only 8-15% were prepared by calcination of silica impregnated with Cu(II)-poly(propylene imine) dendrimer complexes of varying stoichiometry. The size and size distribution of the copper oxide nanoparticles are tunably controlled by the ratio of the Cu(II) to the terminal primary amines in the copper-dendrimer complex, DAB-Am n -Cu(II) x , the surface coverage of the DAB-Am n -Cu(II) x , and the impregnation procedure. This method is anticipated to be useful in the preparation of other metal oxide nanoparticles, e.g., Ni and Fe, and with other oxide substrates.