Global and regional heterogeneity of lung aeration in neonates with different respiratory disorders: a physiological, observational study.

BACKGROUND.: Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). We hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support. METHODS.: Observational, prospective study. Neonates with respiratory distress syndrome (RDS), transient tachypnea (TTN), evolving bronchopulmonary dysplasia (BPD) and neonatal ARDS (NARDS) were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and inter-patient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes. RESULTS.: 230 (50 RDS, TTN or evolving BPD and 80 NARDS) patients were studied. Intra-patient aeration heterogeneity was higher in TTN (mean: 61% [standard deviation: 33%]) and evolving BPD (mean: 57% [standard deviation: 20%], p<0.001), with distinctive aeration distributions. Inter-patient aeration heterogeneity was high for all disorders (Gini-Simpson index: between 0.6 and 0.72) except RDS (Gini-Simpson index: 0.5) whose heterogeneity was significantly lower than all others (p<0.001). NARDS and evolving BPD had the most diffuse injury and worst gas exchange metrics. Regional aeration heterogeneity was mostly localized in upper anterior and posterior zones. Aeration heterogeneity and total lung aeration had an exponential relationship (p<0.001; adj-R 2=0.62). Aeration heterogeneity is associated with greater total lung aeration (i.e., higher heterogeneity means a relatively higher proportion of normally aerated lung zones, thus greater aeration; p<0.001; adj-R 2=0.83) and better oxygenation metrics upon multivariable analyses. CONCLUSIONS.: Global aeration heterogeneity and regional aeration heterogeneity differ amongst neonatal respiratory disorders. TTN and evolving BPD have the highest intra-patient aeration heterogeneity. TTN, evolving BPD and NARDS have the highest inter-patient aeration heterogeneity, but the latter two have the most diffuse injury and worst gas exchange. Higher aeration heterogeneity is associated with better total lung aeration and oxygenation.

Critical care of severe bronchiolitis during shortage of ICU resources.

Large seasonal outbreaks of bronchiolitis put pressure on healthcare systems and particularly on intensive care units (ICUs). ICU admission is necessary to provide respiratory support to the severest cases, otherwise bronchiolitis can result in substantial mortality. ICU resources are often insufficient and there is scant evidence to guide the ICU clinical management. Most available studies do not cover the ICU-admitted cases and do not consider the associated public health issues. We review this topic through a multidisciplinary approach from both the clinical and public health perspectives, with an analysis based on pathophysiology and cost-effectiveness. We suggest ways to optimise respiratory care, minimise ICU stay, "protect" ICU beds and, whenever possible, make them available for other critically ill children. We also provide guidance on how to prepare ICUs to work under stressful conditions due to outbreaks and to reduce the risk of nosocomial cross-contamination, particularly in ICUs caring for high-risk children. Funding: None.

Inspiratory-expiratory variation of pleural line thickness in neonates with and without acute respiratory failure.

BACKGROUND: There are relatively few data about the ultrasound evaluation of pleural line in patients with respiratory failure. We measured the pleural line thickness during different phases of the respiratory cycle in neonates with and without acute respiratory failure as we hypothesized that this can significantly change. METHODS: Prospective, observational, cohort study performed in an academic tertiary neonatal intensive care unit recruiting neonates with transient tachypnoea of the neonate (TTN), respiratory distress syndrome (RDS) or neonatal acute respiratory distress syndrome (NARDS). Neonates with no lung disease (NLD) were also recruited as controls. Pleural line thickness was measured with high-frequency ultrasound at end-inspiration and end-expiration by two different raters. RESULTS: Pleural line thickness was slightly but significantly higher at end-expiration (0.53 [0.43-0.63] mm) than at end-inspiration (0.5 [0.4-0.6] mm; p = 0.001) for the whole population. End-inspiratory (NLD: 0.45 [0.38-0.53], TTN: 0.49 [0.43-0.59], RDS: 0.53 [0.41-0.62], NARDS: 0.6 [0.5-0.7] mm) and -expiratory (NLD: 0.47 [0.42-0.56], TTN: 0.48 [0.43-0.61], RDS: 0.53 [0.46-0.65], NARDS: 0.61 [0.54-0.72] mm) thickness were significantly different (overall p = 0.021 for both), between the groups although the absolute differences were small. The inter-rater agreement was optimal (ICC: 0.95 (0.94-0.96)). Coefficient of variation was 2.8% and 2.5% for end-inspiratory and end-expiratory measurements, respectively. These findings provide normative data of pleural line thickness for the most common forms of neonatal acute respiratory failure and are useful to design future studies to investigate possible clinical applications.

Effect of preterm chorioamnionitis on lung ultrasound score used to guide surfactant replacement.

OBJECTIVE: Lung ultrasound score (LUS) accurately guides surfactant replacement in preterm neonates with respiratory distress syndrome due to surfactant deficiency. However, surfactant deficiency is not the unique pathobiological feature, as there may be relevant lung inflammation, such as in certain cases of clinical chorioamnionitis (CC). We aim to investigate if CC influences LUS and ultrasound-guided surfactant treatment. DESIGN: Retrospective (2017-2022), large, cohort study targeted to recruit a homogeneous population treated with unchanged respiratory care policy and lung ultrasound protocol. Patients with (CC+: 207) and without (CC-: 205) chorioamnionitis were analyzed with propensity score matching and subsequent additional multivariate adjustments. RESULTS: LUS was identical at unmatched and matched comparisons. Consistently, at least one surfactant dose was given in 98 (47.3%) and 83 (40.5%) neonates in the CC+ and CC- matched cohorts, respectively (p = .210). Multiple doses were needed in 28 (13.5%) and 21 (10.2%) neonates in the CC+ and CC- cohorts, respectively (p = .373). Postnatal age at surfactant dosing was also similar. LUS was higher in patients who were diagnosed with neonatal acute respiratory distress syndrome (NARDS) (CC+ cohort: 10.3 (2.9), CC- cohort: 11.4 (2.6)), than in those without NARDS (CC+ cohort: 6.1 (3.7), CC- cohort: 6.2 (3.9); p < .001, for both). Surfactant use was more frequent in neonates with, than in those without NARDS (p < .001). Multivariate adjustments confirmed NARDS as the variable with greater effect size on LUS. CONCLUSIONS: CC does not influence LUS in preterm neonates, unless inflammation is enough severe to trigger NARDS. The occurrence of NARDS is key factor influencing the LUS.

Ultra-high frequency lung ultrasound in preterm neonates: a test validation study on interpretation agreement and reliability.

OBJECTIVE: To verify if increasing frequency, through the use of ultra-high frequency transducers, has an impact on lung ultrasound pattern recognition. DESIGN: Test validation study. SETTING: Tertiary academic referral neonatal intensive care unit. PATIENTS: Neonates admitted with respiratory distress signs. INTERVENTIONS: Lung ultrasound performed with four micro-linear probes (10, 15, 20 and 22 MHz), in random order. Anonymised images (600 dpi) were randomly included in a pictorial database: physicians with different lung ultrasound experience (beginners (n=7), competents (n=6), experts (n=5)) blindly assessed it. Conformity and reliability of interpretation were analysed using intraclass correlation coefficient (ICC), area under the curve (AUC) of the multi-class ROC analysis, correlation and multivariate linear regressions (adjusting for frequency, expertise and their interaction). OUTCOME MEASURES: A (0-3) score based on classical lung ultrasound semiology was given to each image as done in the clinical routine. RESULTS: ICC (0.902 (95% CI: 0.862 to 0.936), p<0.001) and AUC (0.948, p<0.001) on the whole pictorial database (48 images acquired on 12 neonates), and irrespective of the frequency and physicians' expertise, were excellent. Physicians detected more B-lines with increasing frequency: there was a positive correlation between score and frequency (ρ=0.117, p=0.001); multivariate analysis confirmed the score to be higher using 22 MHz-probes (ß=0.36 (0.02-0.7), p=0.041). CONCLUSION: Overall conformity and reliability of interpretations of lung ultrasound patterns were excellent. There were differences in the identification of the B-patterns and severe B-patterns as increasing probe frequency is associated with higher score given to these patterns.

Effect of Different Probes and Expertise on the Interpretation Reliability of Point-of-Care Lung Ultrasound.

BACKGROUND: The effect of different probes and operator experience on the reliability of lung ultrasound (LU) interpretation has not been investigated. We studied the effect of probes and operator experience on the interpretation reliability of LU in critically ill neonates. METHODS: This was a prospective, blind, cohort study enrolling patients with basic patterns ("B," "severe B," consolidation). Patients were scanned with microlinear (15 MHz; L15), phased-array sectorial (6-12 MHz; S7), and microconvex (8 MHz; C8) probes, in random order. Static images were acquired in high resolution, anonymized, and included in a pictorial database in random sequences. Seventeen clinicians with different LU experience were asked to blindly assess the pictorial database. Interrater agreement and interpretation reliability were analyzed. Subanalyses according to expertise and probe, and multivariate linear regression (including an "expertise × probe" interaction factor), were also performed. RESULTS: The agreement tends to be lower and more heterogeneous for residents (intraclass correlation coefficient [ICC], 0.82 [95% CI, 0.74-0.9], P < .001; I2, 67%, P = .04) and for fellows (ICC, 0.93 [95% CI, 0.9-0.97], P < .001; I2, 69%, P = .04), especially when using nonlinear probes, compared with senior physicians (ICC, 0.95 [95% CI, 0.93-0.96], P < .001; I2, 0%, P = .433). Area under the curve (AUC) values were high for all probes (L15, 0.96 [95% CI, 0.93-0.99]; C8, 0.91 [95% CI, 0.85-0.98]; S7, 0.86 [95% CI, 0.82-0.91]) and physicians (senior physicians, 0.95 [95% CI, 0.83-0.99]; fellows, 0.95 [95% CI, 0.75-0.99]; residents, 0.86 [95% CI, 0.5-0.99]). Worse reliability and higher heterogeneity were found when the evaluation was performed by residents (AUC, 0.9 [95% CI, 0.85-0.94], P < .01; I2, 93.6%, P < .001) than by fellows (AUC, 0.99 [95% CI, 0.9-0.999], P < .001; I2, 34.3%, P = .09) and/or by senior physicians (AUC, 0.99 [95% CI, 0.9-0.999], P < .001; I2, 18%, P = .236). The "expertise × probe" interaction factor was associated with lower ICC (standardized regression coefficient ß, -0.69; P < .0001; adjusted R2, 0.99) and AUC (standardized regression coefficient ß, -0.76; P < .0001; adjusted R2, 0.98). CONCLUSIONS: LU interpretation in neonates shows good interrater agreement and reliability, irrespective of the probe and rater expertise. The use of nonlinear probes by novice operators is associated with the lowest agreement and reliability.

Reduction of CFU-GM and circulating hematopoietic progenitors in a subgroup of children with chronic neutropenia associated with severe infections and delayed recovery.

Myelopoiesis was evaluated in 66 pediatric patients with chronic neutropenia who were positive for anti-neutrophil antibodies (median age at diagnosis: 11 months, median neutrophil count at diagnosis: 419/µl). Other causes of neutropenia were excluded. Bone marrow morphology, clonogenic tests and/or the peripheral blood CD 34+ cell count, and apoptotic rate were evaluated in 61 patients with neutropenia lasting > 12 months or severe infections. The peripheral blood CD 34+ cell count and apoptotic rate were evaluated in five patients with shorter neutropenia. The median follow-up time was 29 months (range 7-180 months). Forty-seven patients (71.2%) had a spontaneous recovery after 7-180 months (median 29 months). The group of patients younger than 24 months at diagnosis (n = 50) had a higher probability of recovery (40/50 vs. 7/16 χ2 p<0.01) with a shorter period of neutropenia (median 26 versus 47 months, Kaplan-Meier analysis p = 0.001). The colony-forming units-granulocyte-macrophage (CFU-GM) were significantly decreased in 26/35 patients (74%) evaluated for clonogenic tests. All patients with normal CFU-GM recovered (9/9 patients); whereas, neutropenia persisted in 12/26 patients with reduced CFU-GM (46%, Pearson χ2 p = 0.02). In 36/55 (65%) patients evaluated by flow cytometry we observed reduced circulating CD34+ cells compared with controls of the same age. An increase in the circulating CD34+ cell apoptotic rate was observed in 28/55 patients (51%). Infections requiring hospitalization were observed in 9/18 (50%; Pearson χ2, p = 0.03) patients with both decreased circulating CD34+ cells and increased CD34+ apoptotic rates. In the group aged < 24 months, we observed a significant correlation between the persistence of neutropenia and decreased circulating CD34+ cells (Pearson χ2 p = 0.008). In conclusion, reduced CFU-GM and circulating hematopoietic progenitors were observed in a subgroup of children with chronic neutropenia who were positive for anti-neutrophil antibodies and had a higher incidence of severe infections and delayed spontaneous remission.

Very long-term results of surgical and transcatheter ablation of long-standing persistent atrial fibrillation.

BACKGROUND: New hybrid approaches for atrial fibrillation (AF) ablation, combining surgical and percutaneous procedures, are emerging to enhance the long-term success rate of these 2 procedures severally considered. Recent guidelines underline the need for long-term follow-up to really assess the efficacy of AF ablation. METHODS: From 2000 to 2002, 33 patients with long-standing persistent AF and valvular heart disease underwent valve surgery and cryoablation (pulmonary veins isolation and mitral isthmus and roof line lesions). The surgically created ablation scheme was validated with electroanatomic mapping and percutaneous radiofrequency ablation was performed in case of lesion incompleteness. RESULTS: In 19 of 33 patients (58%) the electroanatomic mapping showed a complete lesion scheme, which increased to 79% (26 of 33) with the addition of radiofrequency ablation. At the mean follow-up of 10.7 ± 3.1 years, 73% (24 of 33) of patients were in sinus rhythm (SR), whereas 27% had permanent AF. At the end of follow-up 81% of patients with a complete lesion scheme were in SR, while 43% with an incomplete one maintained SR (p = 0.048). CONCLUSIONS: In patients with long-standing persistent AF and valvular heart disease, the hybrid approach with surgical cryoablation consisting of pulmonary veins isolation and left atrial linear lesions combined with transcatheter radiofrequency ablation was highly effective in maintaining SR for a very long-term follow-up. Electrophysiological evaluation, to validate the transmurality of the surgical lesions and to complete the lesion scheme applying radiofrequency energy, improved the long-term efficacy.

Linear cryoablation of the left atrium versus pulmonary vein cryoisolation in patients with permanent atrial fibrillation and valvular heart disease: correlation of electroanatomic mapping and long-term clinical results.

BACKGROUND: The aim of this study was to clarify the role of pulmonary vein isolation (PVI) alone versus left atrial linear lesions in the treatment of permanent atrial fibrillation (AF) in patients with left atrial dilatation and valvular disease. The primary end point was to assess the persistence of sinus rhythm (SR) off antiarrhythmic drugs (AADs) at 2-year follow-up and to correlate clinical outcome with surgical results validated with electroanatomic mapping (EAM). METHODS AND RESULTS: A total of 105 patients with permanent AF undergoing valve surgery were assigned to 3 different groups: in groups "U" and "7," left atrial linear cryoablation was performed, whereas in group "PV" patients, anatomic cryoisolation of pulmonary veins only was performed. In groups U and 7, SR was achieved in 57% of patients, whereas it was achieved in 20% of PV patients during 2-year follow-up. In the first 51 patients, the ablation schemes were validated with EAM. The EAM showed that the U lesion was never obtained: in 59% of these patients, a complete 7 lesion was achieved instead; in the 7 group, a complete 7 lesion was present in 65% of patients, whereas a complete PVI was obtained in 71% of patients. Considering patients in whom a complete 7 lesion was demonstrated with the EAM, SR without AADs was achieved in 86% of patients, whereas only 25% of patients with complete PVI were in SR without AADs. CONCLUSIONS: In patients with permanent AF, left atrial dilatation and valvular heart disease linear lesions in the posterior region of the left atrium are more effective than PVI alone. With cryoablation, the surgical intent is fulfilled in only approximately 65% of the cases. Knowing the real anatomic and electrophysiological effects of surgical ablation is necessary to correctly interpret the clinical outcome.

Cryoenergy catheter ablation: a new technique for treatment of permanent junctional reciprocating tachycardia in children.

INTRODUCTION: Permanent junctional reciprocating tachycardia (PJRT) is an infrequent form of reciprocating tachycardia, almost incessant from childhood and usually refractory to drug therapy. Radiofrequency catheter ablation currently is the first-line therapy for PJRT, but its application in the septal region may be associated with complications. In contrast, cryoenergy has several advantages, such as the ability to test the effects of ablation while the lesion is still forming, thus reducing the number of ineffective, useless, and potentially harmful lesions. The aim of this study was to investigate the potential clinical utility of percutaneous cryoenergy catheter ablation for treatment of pediatric patients with PJRT. METHODS AND RESULTS: Four patients (age 14 +/- 5 years; mean +/- SD) with a clinical diagnosis of PJRT underwent catheter cryoablation. The ablation was successfully accomplished in 4 (100%) of 4 patients. The mean +/- SD number of cryoapplications was 1.8 +/- 0.8, and from 1 to 6 cryomappings were performed for each permanent cryolesion. The successful site was in the mid-septal region (2 patients), at the coronary sinus orifice (1 patient), and in the middle cardiac vein (1 patient). No complications with cryoablation were reported, nor was there prolongation of the AH interval during cryomapping or cryoablation. No pain was reported by patients during the cryoenergy catheter ablation procedure. PJRT recurrence occurred in 1 patient who underwent a second successful cryoablation procedure. CONCLUSION: The outcomes of cryoenergy catheter ablation in these 4 patients treated for PJRT suggest that cryoablation is a safe, effective, and pain-free technique for treating pediatric patients with PJRT.