Intubation and Lower Saturation in the Delivery Room are Associated with Balloon Atrial Septostomy in Neonates with Transposition of the Great Arteries.

OBJECTIVE: To identify delivery room (DR) characteristics of patients with transposition of the great arteries (TGA) who underwent preoperative balloon atrial septostomy (BAS). STUDY DESIGN: Retrospective cohort study of all patients with prenatally diagnosed TGA delivered at our center between 2013 and 2023 who underwent arterial switch operation during the newborn admission. RESULTS: A total of 168 patients were included (median gestational age 39.5 weeks, 64% male, 33% with ventricular septal defect [VSD], 8% with aortic arch hypoplasia). BAS was performed in 84 patients (50%). Patients who underwent BAS had higher proportion of intubation in the DR (87% vs. 33%, p<0.001), lower maximum oxygen saturation in the first 10 minutes (64% vs. 74%, p<0.001) and 20 minutes (71% vs. 81%, p<0.001) of life, and lower maximum oxygen saturation at any point in the DR (79% vs. 87%, p<0.001). Adjusting for confounders (VSD, aortic arch anomaly, 5-minute Apgar, birth weight), intubation in the DR (adjusted odds ratio [aOR] 9.5, 95% CI 3.9, 25.0) and lower maximum oxygen saturation in the DR (aOR 0.9, 95% CI 0.8, 0.9) were independently associated with BAS. By receiver operating characteristic analysis, a maximum oxygen saturation of less than 86% at any timepoint in the DR discriminated for BAS with a specificity of 0.88, sensitivity of 0.70, and area under the curve of 0.82. CONCLUSIONS: Intubation and lower oxygen saturation in the DR are independently associated with BAS in patients with TGA born at our center. A maximum DR saturation of less than 86% best discriminates patients who undergo BAS in our population.

Coil Embolization of a Ruptured Mycotic Coronary Artery Aneurysm in a Pediatric Patient.

Mycotic coronary artery aneurysms are rare but have a high risk of mortality. Traditional management is surgical, but percutaneous intervention can be performed in patients with high surgical risk. In this report, we describe a case of mycotic coronary aneurysm in a pediatric patient successfully managed with percutaneous coil embolization. (Level of Difficulty: Advanced.).

Lung and Pleural Findings of Children with Pulmonary Vein Stenosis with and without Aspiration: MDCT Evaluation.

Purpose: To retrospectively compare the lung and pleural findings in children with pulmonary vein stenosis (PVS) with and without aspiration on multidetector computed tomography (MDCT). Materials and Methods: All consecutive children (≤18 years old) with PVS who underwent thoracic MDCT studies from August 2004 to December 2021 were categorized into two groups: children with PVS with aspiration (Group 1) and children with PVS without aspiration (Group 2). Two independent pediatric radiologists retrospectively evaluated thoracic MDCT studies for the presence of lung and pleural abnormalities as follows: (1) in the lung (ground-glass opacity (GGO), consolidation, nodule, mass, cyst(s), interlobular septal thickening, and fibrosis) and (2) in the pleura (thickening, effusion, and pneumothorax). Interobserver agreement between the two reviewers was evaluated by the proportion of agreement and the Kappa statistic. Results: The final study population consisted of 64 pediatric patients (36 males (56.3%) and 43 females (43.7%); mean age, 1.7 years; range, 1 day−17 years). Among these 64 patients, 19 patients (29.7%) comprised Group 1 and the remaining 45 patients (70.3%) comprised Group 2. In Group 1 (children with PVS with aspiration), the detected lung and pleural MDCT abnormalities were: GGO (17/19; 89.5%), pleural thickening (17/19; 89.5%), consolidation (16/19; 84.5%), and septal thickening (16/19; 84.5%). The lung and pleural MDCT abnormalities observed in Group 2 (children with PVS without aspiration) were: GGO (37/45; 82.2%), pleural thickening (37/45; 82.2%), septal thickening (36/45; 80%), consolidation (3/45; 6.7%), pleural effusion (1/45; 2.2%), pneumothorax (1/45; 2.2%), and cyst(s) (1/45; 2.2%). Consolidation was significantly more common in pediatric patients with both PVS and aspiration (Group 1) (p < 0.001). There was high interobserver agreement between the two independent reviewers for detecting lung and pleural abnormalities on thoracic MDCT studies (Kappa = 0.98; CI = 0.958, 0.992). Conclusion: Aspiration is common in pediatric patients with PVS who undergo MDCT and was present in nearly 30% of all children with PVS during our study period. Consolidation is not a typical radiologic finding of PVS in children without clinical evidence of aspiration. When consolidation is present on thoracic MDCT studies in pediatric patients with PVS, the additional diagnosis of concomitant aspiration should be considered.

Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis.

Intraluminal pulmonary vein stenosis is a disease with significant morbidity and mortality, though recent progress has been made using multimodal therapy with antiproliferative agents. The aim of this study was to evaluate the association between aspiration and poor treatment response in patients with intraluminal pulmonary vein stenosis. A retrospective, single-center cohort analysis was performed of patients treated with a combination of imatinib mesylate and multimodal anatomic relief between March 2009 and November 2019. Analysis focused on 2-ventricle patients due to small numbers and clinical heterogeneity of single ventricle patients. Among the 84 patients included, 15 had single ventricle physiology and 69 had 2-ventricle physiology. Among the 2-ventricle group, multivariable analysis revealed that patients with clinical aspiration had nearly five times higher odds of poor treatment response than patients without aspiration (OR 4.85, 95% CI [1.37, 17.2], p = 0.014). Furthermore, male patients had higher odds of poor treatment response than their female counterparts (OR 3.67, 95% CI [1.04, 12.9], p = 0.043). Aspiration is a novel, potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology.

Cholestasis affects enteral tolerance and prospective weight gain in the NICU.

BACKGROUND: Intestinal Failure-Associated Liver Disease is characterized by cholestasis and hepatic dysfunction due to parenteral nutrition (PN) therapy. We described key features of cholestatic infants receiving PN to assess overall outcomes in this population at our institution. METHODS: This is a retrospective single center study of 163 neonates grouped into cholestatic (n = 63) and non-cholestatic (n = 100) as defined by peak conjugated bilirubin of ≥2.0 mg/dL or < 0.8 mg/dL, respectively. Univariate and multiple regression models were used to study associations between variables and outcomes of interest. RESULTS: Lower Apgar scores (4 ± 3 vs. 6 ± 3, p-value = <0.005 at 1 min; 6 ± 2 vs. 7 ± 2, p < 0.005 at 5 min) and lower birth weight (adj ß [SE] = 0.62 [0.27], p-value = 0.024) were risk factors for developing cholestasis. Cholestatic infants were more likely to have had gastrointestinal surgery (31 [49%] vs. 15 [15%], p-value <0.005), received PN for a longer duration (40 ± 39 days vs. 11 ± 7 days, p-value <0.005), and started enteral feeds later in life (86 ± 23 days vs. 79 ± 20 days, p-value <0.005) when compared to non-cholestatic infants. Weight percentiles in cholestatic infants were lower both at hospital discharge (14 ± 19 vs. 24 ± 22, p-value <0.005) and at 6 months of age (24 ± 28 vs. 36 ± 31, p-value = 0.05). CONCLUSIONS: Cholestasis in the NICU is a multifactorial process, but it has a long lasting effect on prospective weight gain in infants who receive PN in the NICU. This finding highlights the importance of follow-up for adequate growth and the potential benefit from aggressive nutritional support.

Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists.

Diacylglycerol kinase alpha (DGKα) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Recently, DGKα was identified as a therapeutic target in various cancers, as well as in immunotherapy. Application of small-molecule DGK inhibitors, R59022 and R59949, induces cancer cell death in vitro and in vivo. The pharmacokinetics of these compounds in mice, however, are poor. Thus, there is a need to discover additional DGK inhibitors not only to validate these enzymes as targets in oncology, but also to achieve a better understanding of their biology. In the present study, we investigate the activity of ritanserin, a compound structurally similar to R59022, against DGKα. Ritanserin, originally characterized as a serotonin (5-HT) receptor (5-HTR) antagonist, underwent clinical trials as a potential medicine for the treatment of schizophrenia and substance dependence. We document herein that ritanserin attenuates DGKα kinase activity while increasing the enzyme's affinity for ATP in vitro. In addition, R59022 and ritanserin function as DGKα inhibitors in cultured cells and activate protein kinase C (PKC). While recognizing that ritanserin attenuates DGK activity, we also find that R59022 and R59949 are 5-HTR antagonists. In conclusion, ritanserin, R59022 and R59949 are combined pharmacological inhibitors of DGKα and 5-HTRs in vitro.

Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight.

Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.