Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Severe Bartter syndrome type 1: Prompt postnatal management thanks to antenatal identification of SLC12A1 pathogenic variants.

Bartter syndrome (BS) refers to a group of hereditary kidney disorders. One antenatal form is Bartter syndrome type 1 (BS1), caused by pathogenic variants in the SLC12A1 gene. We report a case of BS1 presenting with severe polyhydramnios. The fetus was found to carry three pathogenic variants of SLC12A1, leading to the antenatal diagnosis of BS1 and its prompt management. At age 18 days, clinical conditions were complicated by the onset of sepsis requiring supportive measures as well as steroid and antibiotic therapy. Any newborn with an antenatal history of polyhydramnios or postnatal polyuria should be suspected of having BS, since delayed diagnosis may lead to rapid renal failure.

Dilated intercellular space diameter as marker of reflux-related mucosal injury in children with chronic cough and gastro-oesophageal reflux disease.

BACKGROUND: The diagnostic corroboration of the relationship between gastro-oesophageal reflux disease (GERD) and chronic cough remains challenging. AIMS: To compare oesophageal mucosal intercellular space diameter (ISD) in children with GERD, children with gastro-oesophageal reflux (GER)-related cough (GrC) and a control group, and to explore the relationship between baseline impedance levels and dilated ISD in children with GER-related cough. METHODS: Forty children with GERD, 15 children with GrC and 12 controls prospectively underwent oesophagogastroduodenoscopy (EGD) with oesophageal biopsies taken 2-3 cm above squamocolumnar junction. ISD were quantified using transmission electron microscopy. Impedance-pH monitoring with evaluation of baseline impedance in the most distal impedance channel was performed in both patient groups. RESULTS: A significant difference in mean ISD values was found between GrC patients (0.9 ± 0.2 µm) and controls (0.5 ± 0.2 µm, P < 0.001), whereas there was no difference between GrC and GERD group (1 ± 0.3 µm, NS). No difference was found in the mean ISD between GrC children with or without pathological oesophageal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 µm), and there was no correlation between ISD and any reflux parameter. Finally, there was no correlation between ISD and distal baseline impedance values (r:-0.35; NS). CONCLUSIONS: In children with reflux-related cough, dilated intercellular space diameter appears to be an objective and useful marker of oesophageal mucosal injury regardless of acid exposure, and its evaluation should be considered for those patients where the diagnosis is uncertain. In children with reflux-related cough, baseline impedance levels have no role in identifying reflux-induced oesophageal mucosal ultrastructural changes.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease.

BACKGROUND: Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro-esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease. METHODS: Fifteen children (median age: 11.2 years) with NERD, and 11 with ERD (median age: 9.6 years) were prospectively studied. All patients underwent upper endoscopy. Biopsies were taken 2-3cm above the Z-line, and ISD was measured using transmission electron microscopy. All patients underwent impedance pH-monitoring, and baseline impedance levels were assessed in the most distal impedance channel. KEY RESULTS: Mean (±SD) ISD did not differ between NERD (1.0±0.3µm) and ERD (1.1 ± 0.3 µm, ns). Considering all patients together, no correlation was found between distal baseline impedance and ISD (r: -0.15; ns). Conversely, negative correlations were found between distal baseline impedance and acid exposure time (r: -0.76; P<0.001), long-lasting reflux episodes (r: -0.78; P<0.001), acid reflux episodes (r: -0.62; P<0.001), and acid clearance time (r: -0.79; P<0.001). Distal baseline impedance was significantly lower in ERD [1455 (947-2338) Ω] than in NERD children [3065 (2253-3771) Ω; P<0.01]. CONCLUSIONS & INFERENCES: In children with GERD baseline impedance levels are not useful in predicting reflux-induced ultrastructural changes in the esophageal mucosa, despite their ability to discriminate between NERD and ERD.

Reflux oesophagitis in children; the role of endoscopy. A multicentric Italian survey.

BACKGROUND: The decision whether to perform endoscopy in children with suspected reflux oesophagitis is not a straightforward one. Few symptoms are specific for oesophagitis and the diagnosis is not always correlated even to visual findings on endoscopy. AIM: The aim of this study was to define the role of endoscopy and especially of histology in the diagnosis of reflux oesophagitis and to examine the correlations between symptoms, endoscopic findings and histology in children with suspected gastroesophageal reflux disease. PATIENTS AND METHODS: One hundred and thirty-six patients with a clinical diagnosis of reflux oesophagitis, aged 1-18 years (mean 8.43; standard deviation +/-4.4), were enrolled from 12 Italian Paediatrics Gastroenterology Centres; symptom score, endoscopic and histologic oesophagitis scores were observed before and after therapy with proton pump inhibitors. RESULTS: Before therapy, a high correlation between the prevailing symptom score and endoscopic score was demonstrated, but not with histologic score: there was a significant tendency for histologic grade to exceed visual findings. After therapy, endoscopic score and histologic score were significantly improved. CONCLUSIONS: Oesophageal biopsies increase the diagnostic accuracy of upper endoscopy. Histologic grading is often much more important than the endoscopic appearance, so that endoscopic oesophageal biopsies are very important aids in the diagnosis of oesophagitis. Appropriate clinical evaluation of symptoms must occur before endoscopic examination.

Synthesis and in vitro selective anti-Helicobacter pylori activity of pyrazoline derivatives.

In order to develop new anti-Helicobacter pylori agents, a series of N1-substituted 3,5-diphenyl pyrazolines P1-P13 was prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. The same derivatives exhibited a significant degree of activity against a range of H. pylori strains, including those resistant to the reference compound metronidazole. Among the prepared compounds those with an N1-acetyl group and a 4-methoxy substituent in the 5-phenyl ring showed the best activity against H. pylori metronidazole resistant strains in the 1-4 microg/mL MIC range.

Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section.

Following studies on the properties of spontaneous plants in Sardinia we have evaluated the tissue regenerating action of a mixture of oily extracts of Hypericum perforatum and Calendula arvensis on surgical wounds from childbirth with caesarean section.

Visual field constriction in children with epilepsy on vigabatrin treatment.

Vigabatrin is considered the drug of choice for infantile spasms and simple and complex partial epilepsy in childhood. Its mechanism of action relies on the irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase. Since June 1997 several articles have been published reporting visual field constriction in adult patients on vigabatrin therapy. Recently, 7 pediatric patients, 1 on vigabatrin monotherapy and 6 on add-on therapy with visual field constriction have been described. We have observed 30 pediatric patients with epilepsy (14 boys and 16 girls), ages ranging from 4 to 20 years (mean: 11 years and 2 months) treated with vigabatrin for infantile spasms, simple and complex partial epilepsy, who had never complained of ophthalmologic disturbances. Twenty-one patients underwent complete routine ophthalmologic examination (fundus oculi, visual acuity, intraocular pressure, and visual field tests); 9 children (<6 years old) underwent only fundus examination, because collaboration was lacking. We report on 4 children showing constriction of visual field, prevailing in nasal hemifield. In 1 child, visual abnormalities were stable even 10 months after vigabatrin discontinuation, while in another a greater improvement was observed 5 months after discontinuation. The possible mechanisms have been discussed and the cone dysfunction, connected with GABA augmentation in the outer retina, has been outlined. We suggest a possible protocol to control visual abnormalities in epileptic children.

Synthesis and preliminary biological evaluation of 4,6-disubstituted 3-cyanopyridin-2(1H)-ones, a new class of calcium entry blockers.

The preparation of 3-cyano-4,6-diaryl-pyridin-2(1H)-ones 4a-h, calcium entry blockers related to diltiazem, is described starting from 1,3-diaryl-2-propen-1-ones 5. On preliminary pharmacological tests all compounds are active and some of them show calcium antagonistic activity superior or comparable to diltiazem.

[Digestive endoscopy in neonates. Personal experience]. / L'endoscopia digestiva in età neonatale. Esperienza personale.

Gastrointestinal (GI) endoscopy is actually considered an essential diagnostic and therapeutic technique both in pediatrician and in newborn infants. At the moment upper GI endoscopy in neonatal age allows to explore the esophagus, stomach and duodenum; instead lower GI endoscopy easily reaches sigmoid-colon junction. The exploration of other distal parts of bowel is more difficult and with more risks. Therefore it has to be make only if it is necessary. In the newborn this exam should be so fast not to require premedication. In our study, we considered every neonatal patient who underwent GI endoscopy at the "Digestive Endoscopy and Gastroenterology Service of Pediatric Clinic-University of Parma" (from September 1983 to June 2000). We considered two groups of patients: first group: early neonatal age (0-14 days) second group: late neonatal age (15-28 days). We made 127 endoscopies: 112 of these were upper GI. The most frequent symptoms that babies showed and indicated upper GI endoscopy were reflux and/or vomiting (86%). Upper operative GI endoscopies included also 7 esophageal dilatations. The lower GI endoscopies were 15 and in all the cases the indication was intestinal bleeding. We conclude that the GI endoscopy in the neonates shows a diagnostic sensibility and specificity really high and for sure better than the radiology for mucosal lesions. Also GI endoscopy can be not only a very precious diagnostic instrument but also therapeutic in neonatal disease. Considering the age of the little patients, it is very important that only endoscopists with large experience use this technique.

Inhibitory effect of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives on activity of amine oxidases.

A new series of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives was synthesized to ascertain the contribution of substituted phenyl rings present on the 4,5-dihydro-(1H)-pyrazole nucleus to the monoamine oxidases inhibition and bovine serum amine oxidase inhibition. All compounds were tested on bovine brain mitochondria preparation containing flavin-monoamine oxidases and on purified bovine serum amine oxidases, taken as a model of trihydroxyphenylalanine quinone-copper-containing amine oxidases. The 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives showed a good inhibitory activity and belonged to the third generation of monoamine oxidase inhibitors and bovine serum amine oxidase inhibitors which have the advantage of acting through a reversible mode. Furthermore, their activity showed a good degree of selectivity towards the bovine serum amine oxidase inhibition dependent on the substituents present on the phenyl ring at position 5 of the 4,5-dihydro-(1H)-pyrazole.

Synthesis and beta-adrenoreceptor blocking activity of [[3-(alkylamine)-2-hydroxypropyl]oximino]pyridines and O[3-(alkylamine)-2-hydroxypropyl]methylpyridine ketone oximes derivatives.

[[3-(alkylamine)-2-hydroxypropyl]-2-oximino]pyridines and O-[3-(alkylamine)-2-hydroxypropyl]methylpyridine ketone oximes 5a-o were synthesized by a solid-liquid phase-transfer reaction, and their beta-adrenoreceptor blocking activity was evaluated in vitro and in vivo. The replacement of the aryl linked to the oximic carbon of the (methylenaminoxy)methyl moiety with the bioisoster pyridine ring produced a decrease of the beta-adrenergic blocking activity. The polarization of the oximic group, derived from the electron-withdrawing action of the nitrogen atom, is more evident for the 2-oxyminopyridine derivative 5d. But also conformational parameters may play an important role in the variation of activity of the compounds 5d, 5l and 5n. The replacement of the hydrogen linked to the oximic carbon with a methyl group increased the activity of the compounds 5a, 5i, 5m and 5o. The methyl could allow a delocalization of the partial positive charge present on the oximic carbon, but also its lipophilicity contributed to the increment of binding to the receptor site. None of the compounds showed high beta 1 or beta 2 selectivity in vitro. The (R) and (S) isomers of the compound 5a were synthesized and obtained with enantiomeric ratio 7:3 and 6:4, respectively. The binding tests and the pharmacological in vivo results confirmed the in vitro data.