The use of postoperative calibrations in Hirschsprung disease: a practice to reconsider?

PURPOSE: Daily postoperative anal dilations after endorectal pull-through for Hirschsprung disease (HD) are still considered a common practice. We analyzed the potential risks of this procedure and its effectiveness compared to a new internal protocol. METHODS: All infants (< 6 months of age) who underwent transanal endorectal pull-through between January 2021 and January 2023 were prospectively enrolled in a new postoperative protocol group without daily anal dilations (Group A) and compared (1:2 fashion) to those previously treated by postoperative anal dilations (Group B). Patients were matched for age and affected colonic tract. Patients with associated syndromes, extended total intestinal aganglionosis, and presence of enterostomy were excluded. Outcomes considered were: anastomotic complications (stenosis, disruption/leakage), incidence of enterocolitis, and constipation. RESULTS: Eleven patients were included in group A and compared to 22 matched patients (group B). There were no significant differences in the occurrence of anastomotic complications between the two groups. We found a lower incidence of enterocolitis and constipation among group A (p = 0.03 and p = 0.02, respectively). CONCLUSION: A non-dilation strategy after endorectal pull-through could be a feasible alternative and does not significantly increase the risk of postoperative anastomotic complications. Moreover, some preliminary advantages such as lower enterocolitis rate and constipation should be further investigated.

Use of N-Acetylcysteine in Preterm Neonates with Enteral Feeding Intolerance and Intestinal Obstruction: A Case Series and Review of the Literature.

(1) Background: The use of N-acetylcysteine (NAC) to relieve meconium obstruction of prematurity in the first days of life has been reported, with NAC reducing the viscosity of luminal contents by cleaving the disulfide bonds of mucoproteins. However, its use in this population should be further explored since it has been associated with hypernatremia and transient increase in transaminases and bilirubin. (2) Methods: In this retrospective study, we included neonates admitted because of enteral feeding intolerance and intestinal obstruction from 2019 to 2021 who received NAC as a rescue therapy before explorative laparotomy. (3) Results: We summarized the clinical presentation of six preterm neonates with enteral feeding intolerance and intestinal obstruction who received NAC as a rescue therapy. Four infants (66.7%) gradually improved without the need for explorative laparotomy, whereas two infants (33.3%) underwent the creation of an ileostomy. No cases of hypernatremia or hepatic derangement associated with NAC therapy were observed. (4) Conclusions: We described the use of NAC treatment by nasogastric tube and/or rectal enemas in preterm infants with enteral feeding intolerance and intestinal obstruction after a multidisciplinary assessment, but the limited sample size did not allow us to obtain definitive conclusions and further research is needed in this field, given the limited evidence about NAC treatment in preterm infants.

A new variant in the GATA6 gene associated with tracheoesophageal fistula, pulmonary vein stenosis and neonatal diabetes.

INTRODUCTION: GATA6 is a gene that encodes a transcription factor with a key role in the development of several organ systems, including the development of the pancreas. It is associated with neonatal diabetes but also with other extra-pancreatic anomalies. CASE PRESENTATION: This report describes the association of tracheoesophageal fistula (TEF), pulmonary vein stenosis (PVS), and neonatal diabetes caused by a novel mutation of the GATA6 gene in a small-for-gestational-age male neonate born at 32 weeks of gestation. Next-Generation Sequencing revealed the novel heterozygous variant c.1502C>G in the GATA6 gene, which determines the introduction of the premature stop codon p.Ser501Ter at the protein level. This de novo nonsense variant was not detected in the analyzed parental DNA samples and has not been previously described in the literature. At about two months of life, a PVS was suspected. The PVS progressively increased with the development of an intramural component, resulting in severe postcapillary pulmonary hypertension. The child died at about 4 months of life. CONCLUSION: TEF can be associated with GATA6 variants. In the case of neonatal diabetes and TEF, neonatologists should be aware of this association and should also investigate the child for complex congenital heart disorders, such as in our case, with a cardiac computed tomography.

Biliary atresia in preterm infants: a single center experience and review of literature.

Introduction: The diagnosis of biliary atresia (BA) remains challenging, and there is still uncertainty regarding the optimal time to perform a Kasai portoenterostomy (KPE). Little is known about the difficulties in the diagnosis and outcomes of BA in preterm infants (PBA). This study, which represents the first Italian report of preterm infants with BA, aims to describe a single-center experience of BA in preterm newborns. Methods: We retrospectively reviewed all infants consecutively diagnosed with BA who underwent a Kasai procedure at the Bambino Gesù Children's Hospital between January 1998 and December 2021. Prematurity was defined as a gestational age (GA) of <37 weeks. Demographic, laboratory, and histology data were recorded, and the main outcomes considered were clearance of jaundice (COJ), native liver survival, and mortality. Results: A total of 21 PBA were compared with 117 term BA controls (TBA). The median GA of PBA was 35.1 (32-36.1) weeks, with a mean birth weight of 2,100 (1,897-2,800) g. Age at first presentation was significantly lower in PBA patients: 46 (22-68) vs. 61 (44-72) days; p = 0.02. The median age at KPE was similar between the two groups: 70 days (33 corrected) for PBA vs. 67 in TBA; p = 0.8. At the time of surgery, median serum bilirubin was lower in the PBA group (7.7 vs. 8.6 mg/dl, p = 0.04). Similarly, the median APRi at the time of KPE was lower but not significant in the PBA group: 1.09 vs. 1.16; p = 0.8. No differences were found in terms of COJ between the PBA and TBA groups: n = 9 (43%) vs. 34 (35%); p = 0.2. Overall native liver survival was similar between the two groups: 8.6 (4.8-12.2) for the PBA group vs. 7.6 (5.6-9.5) years for the TBA group with no significant differences; p = 0.45. Post-KPE native liver survival was similar between the two groups: 38% vs. 52% at 5 years for the TBA and PBA groups, respectively; p = 0.54. Conclusion: The PBA and TBA groups appear to have similar outcomes in terms of COJ, overall native liver survival, and 5-year liver survival. Considering the corrected GA, early KPE is related to lower cholestatic damage. Further multicenter studies are required.

Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery.

INTRODUCTION: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations. METHODS: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects. The survey was conducted contacting all pediatric surgical units performing thoracic surgery. RESULTS: 39 pediatric surgery units (97.5%) participated in the study. 13 centers (33.3%) were classified as high-volume (Group A), while 26 centers (66.7%) were low volume (Group B). Variances in diagnostic imaging protocols were observed, with Group A performing fewer CT scans compared to Group B (p = 0.012). Surgical indications favored operative approaches for asymptomatic CLM and pulmonary sequestrations in both groups, while a wait-and-see approach was common for congenital lobar emphysema. Surgical timing for asymptomatic CLM differed significantly, with most high-volume centers operating on patients younger than 12 months (p = 0.02). Thoracoscopy was the preferred approach for asymptomatic CLM in most of centers, while postoperative long-term follow-up was not performed in most of the centers. CONCLUSION: Thoracoscopic approach seems uniform in asymptomatic CLM patients and variable in symptomatic children. Lack of uniformity in surgical timing and preoperative imaging assessment has been identified as key areas to establish a common national pattern of care for CLM.

Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

Anorectal malformations (ARM) and VACTERL association and severity of congenital heart diseases (CHD): Experience of 396 consecutive patients in a tertiary center.

OBJECTIVE: Congenital heart diseases (CHD) are the most frequently associated anomalies with anorectal malformations (ARM). Nevertheless, many specific aspects of CHD in ARM patients have yet to be studied. The aims of this study were to evaluate the prevalence and distribution of CHD in neonates-infants with ARM, and to explore whether the severity of ARM, and the presence of VACTERL association, had an impact on CHD rate, severity, and timing at first cardiac surgery. STUDY DESIGN: All consecutive newborn-infants with ARM managed in our tertiary center (January-1999; December-2021) were collected from a prospective database and retrospectively analyzed. Prevalence and distribution of CHD in ARM patients were assessed. Patients were divided into groups depending on ARM severity and presence of VACTERL association. Pairwise comparison for CHD prevalence, severity, and timing at first cardiac surgery was performed between groups. RESULTS: Of 396 ARM patients identified, those with severe ARM showed a higher number of overall CHD compared to patients with non-severe ARM (36.7 % vs. 25.2 %, p = 0.032). VACTERL + patients had a significantly higher prevalence of CHD (73.4 % vs. 16.4 %; p <0.001) and major CHD (51.7 % vs. 26.9 %; p = 0.008) when compared with VACTERL-patients. Furthermore, VACTERL + patients underwent first cardiac surgery at a significantly younger age than VACTERL-patients (5.2 ± 15.2 months vs. 11.9 ± 6.3, p = 0.039). CONCLUSIONS: Patients with severe ARM had a higher number of CHD compared to patients with non-severe ARM. VATERL + patients had significantly more CHD and more severe CHD than VACTERL-patients. Early screening for CHD is strongly recommended in all newborns diagnosed with ARM before surgery. LEVEL OF EVIDENCE: III retrospective comparative study.

Respiratory and Musculoskeletal Long-Term Outcomes after Surgical Resection of Congenital Cystic Adenomatoid Malformation of the Lung in Newborns, Infants, and Toddlers.

INTRODUCTION: The long-term outcomes of children who underwent surgery for congenital cystic adenomatoid malformation of the lung (CCAML) are not well documented, particularly regarding orthopaedic and respiratory follow-up (FU). The aim of this study was to assess the long-term pulmonary and orthopaedic outcomes of surgically treated CCAML in newborns, infants, and toddlers. MATERIALS AND METHODS: Retrospective examination of prospectively recorded data of consecutive patients with CCAML who underwent surgery at our tertiary referral institution from January 2000 to December 2015 (newborns, infants, and toddlers). Clinical, radiological, and surgical data, as well as FU data were revised. A multidisciplinary team followed the patients after discharge at scheduled time points. RESULTS: Seventy-seven patients were included. After surgery, patients were followed for a median of 8 years (range: 1-19 years) until they reached a median age of 8 years (range: 2-19 years). Thirty patients (39%) developed wheezing and 21 (27%) had lower respiratory tract infections (LRTIs) within 4 years of age. However, more than 50% of patients with respiratory symptoms underwent complete remission in the following 4 years. Thirty-one patients (40%) developed at least one minimal musculoskeletal deformity. Eighteen (23%) had scoliosis, 17 (22%) thoracic asymmetry, 10 (12%) pectus excavatum, and 5 (6%) winged scapula. CONCLUSIONS: Patients operated for CCAML had good overall outcomes despite pulmonary symptoms and musculoskeletal sequelae. Even though these issues are frequently paucisymptomatic, trying to use less-invasive procedures (such as minimally axillary open "muscle-sparing" thoracotomy or thoracoscopy) may reduce this burden. A structured multidisciplinary FU is required.

Prevalence of anxiety and depression risk during the prepartum period in the different groups of women and responses from the Italian National Health Service.

BACKGROUND: Specific screening for anxiety and depression in pregnant women is important to identify those at risk and to provide timely intervention. The aims of the study were: 1) to compare the risk of anxiety and depression in four groups of pregnant women belonging to four types of healthcare centers distinguished by the level of risk: at low-risk; at high-risk for an obstetric reason; at high-risk for fetal anomalies; at high-risk for psychiatric conditions and 2) to identify the response that the National Health Service offers to women positively screened for anxiety and depression. METHODS: A cross-sectional study was conducted on 2801 pregnant women, cared for by National Health Service, divided into four groups: 1) low-risk pregnancy (N.=1970); 2) high-risk pregnancy for an obstetric reason (N.=218); 3) high-risk for fetal anomalies (N.=505); and 4) high-risk for psychiatric conditions (N.=108). Participants were screened using the Edinburgh Postnatal Depression Scale, the General Anxiety Disorder, and sociodemographic, anamnestic, and clinic questionnaires. RESULTS: 28.9% of participants obtained an EPDS Score ≥9 and 17.1% a GAD-7 Score ≥8. The group at high-risk for fetal anomalies presented the highest prevalence of anxiety (29.3%) and depression (49.1%) while the group at low risk presented the lowest prevalence of anxiety (13%) and depression (24.6%). The groups at risk for obstetric reasons presented an intermediate prevalence. Psychiatric conditions constituted a higher risk for anxiety than depression. Counselling is recommended for about 70% of women at risk for anxiety and depression. Moreover, about 15% of women positive for screening were initiated into psychotherapy and about 1.5% into pharmacotherapy. 15% of women positive for screening were referred to other specialists. CONCLUSIONS: This study underlined the relevance of a prompt response by the National Health Service to mental health needs, especially in the risk conditions related to obstetric and/or fetal anomalies and psychopathology.

Decreased incidence of late-onset sepsis during the SARS-CoV-2 pandemic in Italy: a multicentric study on a cohort of infants requiring major surgery.

Changes in the organization of the clinical care wards, requested by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, have influenced the environmental circulation of other pathogens. The implementation of prevention procedures may have led to a decrease in the incidence of healthcare-associated infections. We aimed to investigate the impact of prevention and control measures for preventing the COVID-19 spread on the incidence of bacterial sepsis and invasive fungal infections in neonates and infants requiring major surgery. We compared the incidence of bacterial and fungal sepsis and their risk factors observed before the SARS-CoV-2 pandemic (from 01/10/2018 to 29/02/2020) with those observed during the pandemic (from 01/03/2020 to 07/05/2021) in 13 level III Neonatal Intensive Care Units in Italy, through a secondary analysis of data, collected during a prospective multicenter study (REF). The patients enrolled were infants within three months of life, hospitalized in the two periods in the participating centers to undergo major surgery. Among 541 enrolled patients, 324 (59.9%) were born in the pre-pandemic period and 217 (40.1%) during the pandemic. The incidence density (ID) of any infection in the pre-pandemic period was 16.0/1000 patient days versus 13.6/1000 patient days in the pandemic period (p < 0.001). One hundred and forty-five (145/324; 44.8%) patients developed at least one episode of bacterial sepsis in the pre-pandemic period, versus 103/217 (31.8%) patients, during the pandemic (p = 0.539). Concerning fungal sepsis, 12 (3.7%) patients had one episode in the pre-pandemic period versus 11 (5.1%) patients during the pandemic (p = 0.516). The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics pre-surgery, and that of proton pump inhibitors during the SARS-CoV-2 pandemic compared with the previous period. CONCLUSIONS: In our cohort of patients with major surgical needs, the reduction of CVC days, pre-surgery antibiotics administration, and current use of proton pump inhibitors, during the SARS-CoV-2 pandemic, led to a decrease in the incidence of late-onset sepsis. WHAT IS KNOWN: • Most cases of late-onset sepsis in neonates are referred to as central line-associated bloodstream infections. • In adults, the COVID-19 outbreak negatively influenced healthcare-associated infection rates and infection clusters within hospitals. WHAT IS NEW: • In neonates and infants undergoing major surgery the incidence density of infections was lower in the pandemic period than before. • The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics before surgery, and that of proton pump inhibitors during the pandemic compared with previously.

European Paediatric Surgeons' Association Consensus Statement on the Management of Neonatal Ovarian Simple Cysts.

INTRODUCTION: Neonatal ovarian simple cyst management from the pediatric surgical aspect is unclear on cyst size, follow-up, and preferred surgical approach. Therefore, this topic was selected for the 2022 Consensus Session meeting of the European Paediatric Surgeons' Association (EUPSA). METHODS: The literature was reviewed on a predefined set of questions relating to the management of the neonatal ovarian simple cysts by a panel of 7 EUPSA members, on current evidence-based opinion and practice outlined. Each question (1) outcomes of fetal interventions in neonates after birth and consensus on size/timing of intervention, (2) consensus on the type of interventions, and (3) complications in neonatal ovarian cysts and follow-up recommendations in nonoperated/operated cysts, was presented with available evidence to congress session participants. The management approach was agreed by participants and comments were accounted to formulate the consensus statement. RESULTS: There is still limited data on potential benefits and complications of prenatal ultrasound-guided aspiration; however, neonates after such procedures should be followed for 6 months. Neonates with simple ovarian cysts larger than 4 cm should be offered surgical interventions within the 2 weeks of life with complete laparoscopic cyst aspiration and fenestration with bipolar instruments being the preferred approach. Ultrasound follow-up after surgical intervention after 3 months and with the conservative approach after every 3 to 4 months until 1 year. CONCLUSION: A peer-reviewed consensus statement for the management of neonatal ovarian simple cyst was formulated based on current evidence and peer practice. The EUPSA recognizes that the statement can be useful for pediatric surgeons in decision making for this pathology.

Hypospadias management in children with anorectal malformation: a multidisciplinary single center experience.

Anorectal malformation (ARM) is often associated to other congenital malformations, requiring a tailored management. Hypospadias' treatment in ARM is poorly described. Aim of study is to describe our experience in ARM-hypospadias patients especially in relation to occult spinal dysraphism (OSD). ARM patients treated from 1999 to 2022 were retrospectively reviewed, selecting male with hypospadias. Clinical data, hypospadias's severity, ARM sub-type (Group A: perineal fistula; Group B: urethral fistula, bladder fistula, no fistula), OSD, other associated malformations, NLUTD were evaluated. Exclusion criteria: uncomplete data. Among 395 ARMs, 222 were males, 22 (10%) had hypospadias. Two patients were excluded. Group A: 8 patients, Group-B: 12. Hypospadias: proximal 9 patients, distal 11. Neuro-urological evaluation was performed before hypospadias repair. Eleven patients (55%) had OSD. Four OSD patients presented NLUTD and underwent detethering and CIC (two via cystostomy button, two via appendicostomy); two of them had hypospadias repaired. All proximal hypospadias underwent two stages of surgery. Distal hypospadias was corrected in 4/11 cases. Hypospadias is quite common in ARM patients and its surgical management must be scheduled considering the possible OSD and NLUTD, with the possible need for intermittent catheterization. Complexity of ARM and hypospadias appears to be related to each other.

Isoperistaltic gastric tube for long gap esophageal atresia (LGEA) in newborn, infants, and toddlers: a case-control study from a tertiary center.

Background: Limited evidence exists about outcomes after gastric tube formation as "rescue" technique to avoid esophageal replacement in long gap esophageal atresia (LGEA). The last ERNICA Consensus Conference on the Management of LGEA has placed the techniques of gastric tubulization among the priorities for future research. Aims: Evaluate personal experience with Isoperistaltic Gastric Tube (IGT) and compare its outcomes with other more popular techniques for LGEA. Methods: A case-control study has been conducted. A retrospective monocentric analysis of LGEA patients (period: 2010-19) has been conducted in all consecutive IGT patients and each of these has been type matched with two cases of LGEA treated with other techniques. The follow-up (FU) considered was 24-months. Results: IGT and controls showed no statistically significant differences regarding preoperative variables like sex, gestational age, birth weight, syndromes, and EA type. However, IGT patients had a significantly longer esophageal GAP under boost pressure (4.5 vertebral bodies vs. 3.6, p = 0.019) at time of surgery. The analysis showed no statistical difference among the two groups about perioperative outcomes, ICU, or overall postoperative stay. No differences have been shown between IGT and controls during the follow-up regarding GERD, esophagitis, fundoplication, dysphagia, vocal cord paralysis, stenosis, and dilatations, auxologic data, need for anastomosis revision, oral aversion, and death. Conclusions: Isoperistaltic Gastric Tube is safe and effective even in LGEA patients with longer gaps, with good perioperative, post-operative and middle-term outcomes. This procedure may be considered as an alternative to avoid esophageal substitution when a primary anastomosis seems impossible for a residual gap after traction and growth techniques.

Brain cortical assessment by MRI in fetuses with left congenital diaphragmatic hernia.

OBJECTIVE: To evaluate fetal brain development using MRI (magnetic resonance imaging) in CDH (congenital diaphragmatic hernia). METHODS: 52 isolated left CDH and 104 control fetuses were imaged using MRI. Brain morphometry (Biparietal diameter-BPD, brain fronto-occipital diameter-BFOD, third ventricle, posterior ventricles, transcerebellar diameter-TCD, anteroposterior and craniocaudal cerebellar vermis diameter-AP and CC) and cortical structures (bilateral cingulate fissure-CF, insular fissure-IF, insular depth - ID) were compared with controls using Mann-Whitney test. RESULTS: Median gestational age at MRI (p = 0.95)and the median biparietal diameter (p = 0.737) were comparable. Among morphometric parameters, only the brain fronto-occipital diameter was significantly smaller in CDH (p = 0.001) and the third ventricle was significantly greater in CDH (<0.0001). Among cortical structures, the cingulate and insular fissures were significantly deeper in CDH fetuses (p < 0.0001) as the insular depth ID was smaller in CDH (p < 0.03). CONCLUSIONS: CDH fetuses have a smaller fronto-occipital diameter, reduced insular depth, deeper cingulate and insular fissure, and greater third ventricle width as compared to controls. These findings suggest that left CDH may have an impact on fetal brain development with an overall reduction in brain volume.

Early vasopressin infusion improves oxygenation in infants with congenital diaphragmatic hernia.

Objective: Congenital Diaphragmatic Hernia (CDH) is a complex disease including a diaphragmatic defect, lung hypoplasia, and pulmonary hypertension. Despite its increasing use in neonates, the literature on the use of vasopressin in neonates is limited. The aim of this work is to analyze the changes in clinical and hemodynamic variables in a cohort of CDH infants treated with vasopressin. Methods: Among CDH infants managed at the Neonatal Intensive Care Unit (NICU) of our hospital from May 2014 to January 2019, all infants who were treated with vasopressin, because of systemic hypotension and pulmonary hypertension, were enrolled in this retrospective study. The primary outcome was the change in oxygenation index (OI) after the start of the infusion of vasopressin. The secondary outcomes were the changes in cerebral and splanchnic fractional tissue oxygen extraction (FTOEc and FTOEs) at near-infrared spectroscopy, to understand the balance between oxygen supply and tissue oxygen consumption after the start of vasopressin infusion. We also reported as secondary outcomes the changes in ratio of arterial oxygen partial pressure (PaO2) to fraction of inspired oxygen (FiO2), heart rate, mean arterial pressure, serum pH, and serum sodium. Results: We included 27 patients with isolated CDH who received vasopressin administration. OI dramatically dropped when vasopressin infusion started, with a significant reduction according to ANOVA for repeated measures (p = 0.003). A global significant improvement in FTOEc and FTOEs was detected (p = 0.009 and p = 0.004, respectively) as a significant reduction in heart rate (p = 0.019). A global significant improvement in PaO2/FiO2 ratio was observed (p < 0.001) and also at all time points: at 6 h since infusion (p = 0.015), 12 h (p = 0.009), and 24 h (p = 0.006), respectively. A significant reduction in sodium levels was observed as expected side effect (p = 0.012). No significant changes were observed in the remaining outcomes. Conclusion: Our data suggest that starting early vasopressin infusion in CDH infants with pulmonary hypertension could improve oxygenation index and near-infrared spectroscopy after 12 and 24 h of infusion. These pilot data represent a background for planning future larger randomized trials to evaluate the efficacy and safety of vasopressin for the CDH population.

Role of microRNAs in Congenital Diaphragmatic Hernia-Associated Pulmonary Hypertension.

Epigenetic regulators such as microRNAs (miRNAs) have a key role in modulating several gene expression pathways and have a role both in lung development and function. One of the main pathogenetic determinants in patients with congenital diaphragmatic hernia (CDH) is pulmonary hypertension (PH), which is directly related to smaller lung size and pulmonary microarchitecture alterations. The aim of this review is to highlight the importance of miRNAs in CDH-related PH and to summarize the results covering this topic in animal and human CDH studies. The focus on epigenetic modulators of CDH-PH offers the opportunity to develop innovative diagnostic tools and novel treatment modalities, and provides a great potential to increase researchers' understanding of the pathophysiology of CDH.

Clonal Spread of Hospital-Acquired NDM-1-Producing Klebsiella pneumoniae and Escherichia coli in an Italian Neonatal Surgery Unit: A Retrospective Study.

This article reports a rapid and unexpected spread of colonization cases of NDM-1 carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in a neonatal surgical unit (NSU) at Bambino Gesù Children's Hospital in Rome, Italy. Between the 16th of November 2020 and the 18th of January 2021, a total of 20 NDM-1 carbapenemase-producing K. pneumoniae (n = 8) and E. coli (n = 12) were isolated from 17 out of 230 stool samples collected from neonates admitted in the aforementioned ward and time period by an active surveillance culture program routinely in place to monitor the prevalence of colonization/infection with multidrug-resistant Gram-negative microorganisms. All strains were characterized by antimicrobial susceptibility testing, detection of resistance determinants, PCR-based replicon typing (PBRT) and multilocus-sequence typing (MLST). All isolates were highly resistant to most of the tested antibiotics, and molecular characterization revealed that all of them harbored the blaNDM-1 gene. Overall, IncA/C was the most common Inc group (n = 20/20), followed by IncFIA (n = 17/20), IncFIIK (n = 14/20) and IncFII (n = 11/20). MLST analysis was performed on all 20 carbapenemase-producing Enterobacterales (CPE) strains, revealing three different Sequence Types (STs) among E. coli isolates, with the prevalence of ST131 (n = 10/12; 83%). Additionally, among the 8 K. pneumoniae strains we found 2 STs with the prevalence of ST37 (n = 7/8; 87.5%). Although patient results were positive for CPE colonization during their hospital stay, infection control interventions prevented their dissemination in the ward and no cases of infection were recorded in the same time period.