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.

RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation.

The intrinsically disordered RG/RGG repeat domain is found in several nucleolar and P-granule proteins, but how it influences their phase separation into biomolecular condensates is unclear. We survey all RG/RGG repeats in C. elegans and uncover nucleolar and P-granule-specific RG/RGG motifs. An uncharacterized protein, K07H8.10, contains the longest nucleolar-like RG/RGG domain in C. elegans. Domain and sequence similarity, as well as nucleolar localization, reveals K07H8.10 (NUCL-1) to be the homolog of Nucleolin, a protein conserved across animals, plants, and fungi, but previously thought to be absent in nematodes. Deleting the RG/RGG repeats within endogenous NUCL-1 and a second nucleolar protein, GARR-1 (GAR1), demonstrates these domains are dispensable for nucleolar accumulation. Instead, their RG/RGG repeats contribute to the phase separation of proteins into nucleolar sub-compartments. Despite this common RG/RGG repeat function, only removal of the GARR-1 RG/RGG domain affects worm fertility and development, decoupling precise sub-nucleolar structure from nucleolar function.

Lung recruitment strategies and surfactant in neonatal intensive care unit.

Several studies in the lamb model have shown that hyperinflation of the lungs early in life may cause a blunted response to surfactant with signs of lung injury and any attempt to recruit lung volume in the surfactant deficient preterm infant by large lung inflations at birth should be potentially dangerous. As regards the situation when surfactant is given later, as rescue treatment for established RDS, the evidence for a clinically beneficial effect of a recruitment maneuver is yet insufficient and, hopefully, future studies will gather more data on this aspect.

Mitral valve repair for the treatment of degenerative mitral valve disease with or without prosthetic ring annuloplasty: long-term outcomes.

AIM: Aim of the study was to evaluate late outcomes of mitral valve repair with and without the use of prosthetic ring annuloplasty and standardized techniques for the treatment of degenerative mitral regurgitation (MR). METHODS: Three hundred and five patients (mean age 62 ± 12 years) underwent mitral valve repair between January 1992 and February 2010 for degenerative MR. In the last five years, all repair techniques were performed routinely using prosthetic ring annuloplasty, with or without quadrangular or triangular resection of posterior leaflet and/or edge-to-edge technique. Mean follow-up (99% complete) was 78 ± 46 (2-220) months. RESULTS: Operative mortality was 0.9% (3/305), 15-year actuarial survival 82% ± 4%. At 15 years freedom from cardiac death was 89% ± 3.7%, from reoperation 84% ± 5.8%, from endocarditis 100%. Independent predictors of all-causes mortality were advanced age at operation (P=0.0006) and mitral valve repair without reductive prosthetic annuloplasty (P=0.0019). Death for cardiac causes was significantly higher when reductive annuloplasty was performed without the use of prosthetic ring (P<0.01). Late progression to moderate or severe MR was observed in 23/299 patients (7.7%). Independent predictors of progression to moderate or severe MR was annuloplasty without the use of prosthetic ring (P=0.0053) and postoperative residual mild MR (P=0.0014). Reoperation was required in 13/299 patients (4.4%). At 10 years freedom from moderate or severe MR was 86% ± 6% and 92% ± 4% in patients with postoperative absent or trivial residual MR, respectively, as compared to 38% ± 15% in those with postoperative residual mild MR (P<0.0001), freedom from reoperation 94% ± 4% and 90% ± 14% vs. 56% ± 16% (P<0.0001). CONCLUSION: Prosthetic annuloplasty in association with standardized techniques confers over 10 years survival advantage and better durability.

Effectiveness of treatment with surfactant in premature infants with respiratory failure and pulmonary infection.

INTRODUCTION: Surfactant inactivation is present in neonatal pneumonia. MATERIALS AND METHODS: One hundred thirty-nine preterm babies with Birth Weight (BW) < or = 1250 grams were studied and subdivided in two groups: RDS Group, with a diagnosis of "simple" RDS (N 80) and RDS with Pneumonia Group, consisting of babies with a diagnosis of RDS and a positive BALF culture in the first 24-48 h of life (N 59). OUTCOMES: Surfactant administration seems less effective in the latter group, because a significantly higher number of infants needed a second dose of surfactant, compared to the patients suffering from RDS alone. (www.actabiomedica.it).

Target fraction of inspired oxygen during open lung strategy in neonatal high frequency oscillatory ventilation: a retrospective study.

BACKGROUND: There is no agreement to define the target FiO2 to adopt in the lung recruitment phase during HFOV in preterm infants. We report our experience of an optimal lung volume strategy (OLVS), defined as FiO2≤0.25 during the recruitment phase, in a cohort of neonates with gestational age (GA) ≤27 weeks treated with elective HFOV for respiratory distress syndrome (RDS) between July 2006 and September 2008. METHODS: FiO2 used during the recruitment phase was different according to physician' evaluation. 51 newborns were then divided into two groups: patients reaching FiO2≤0.25 (OLVS Group, N.=28), and patients reaching FiO2>0.25 (No-OLVS Group, N.=23). RESULTS: Prior to surfactant administration OLVS Group, respect to No-OLVS Group, received a significantly higher continuous distending pressure (CDP): 12.8±1.1 cmH2O vs 11.2±1.3 cmH2O (P<0.0001) and a significantly lower FiO2: 0.25±0.01 vs 0.35±0.06 (P<0.0001). A multivariate modeling approach confirmed that OLVS was significantly associated to the need for less surfactant doses (OR 0.19[95% CI 0.05-0.84]), a decreased risk of ductus arteriosus surgically ligated (OR 0.13[95% CI 0.02-0.86]) and to a lower number of ventilation hours before extubation: -152 (95% CI -284- -20). CONCLUSION: OLVS to fully recruit the lungs achieving FiO2≤0.25 during elective HFOV is associated with better short-term pulmonary outcomes respect to a strategy where the patients received a FiO2>0.25 during the recruitment phase. Utilizing HFOV in this way provides a more effective means to recruit and protect acutely injured lungs.

Proteomics and neonatal infection.

Antimicrobial peptides plays an important role in the host innate defence network, even in humans. Recent studies demonstrated the capacity of human airways epithelial cells to synthesize antimicrobial peptides, and their multifunctional role in the primary immunity. The presence of ct-defensins in bronchoalveolar lavage fluid (BALF) was investigated in a cohort of preterm newborns with gestational age (GA) < or =30 weeks. BALF samples were analysed by High Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer. Our data show that preterm newborns, also at the lower GA, are able to produce defenses, underlining that their innate defence system is already active before the at-term delivery date.

New concepts and materials in microvascular grafting: prosthetic graft endothelial cell seeding and gene therapy.

Microsurgical free tissue transfer is currently associated with very high success rates and few complications. While interposition vein grafting is clearly an important adjunct to the microsurgeon's armamentarium, it has been associated with higher free flap/replantation failures and complication rates. With appropriate flap planning and surgical techniques, the need for interposition vein grafting should be quite infrequent and hopefully avoided if at all possible. Nevertheless, when necessary, the vein graft remains the gold standard, with virtually all alternative interposition grafts demonstrating lower patency rates. One of the more promising areas of research is the concept of genetic manipulation of the endothelial cell via molecular biological techniques. It is likely that in the near future this may become a clinical reality, not only improving the patency of microsurgical anastomoses and interposition vein grafts, but quite possibly altering the target organ functionally as well.

Total alignment of calcite at acidic polydiacetylene films: cooperativity at the organic-inorganic interface.

Biological matrices can direct the absolute alignment of inorganic crystals such as calcite. Cooperative effects at an organic-inorganic interface resulted in similar co-alignment of calcite at polymeric Langmuir-Schaefer films of 10,12-pentacosadiynoic acid (p-PDA). The films nucleated calcite at the (012) face, and the crystals were co-aligned with respect to the polymer's conjugated backbone. At the same time, the p-PDA alkyl side chains reorganized to optimize the stereochemical fit to the calcite structure, as visualized by changes in the optical spectrum of the polymer. These results indicate the kinds of interactions that may occur in biological systems where large arrays of crystals are co-aligned.

Validity of microsphere model in cerebral blood flow measurement using N-isopropyl-p-(I-123) iodoamphetamine.

A microsphere model is sometimes used when calculating cerebral blood flow (CBF) using N-isopropyl-p-[I-123]iodoamphetamine (IMP), and is based on the assumption that there is essentially no washout of IMP. The validity of a microsphere model was investigated by comparison with the values of CBF obtained by means of a model which takes into consideration the diffusion of IMP from brain tissue to blood (nonmicrosphere model). When calculating CBF by the latter model, the look-up table method was used with expression of the double integral in the model equation by the recursion relations, a method which is useful for obtaining pixel-by-pixel values. The average rate constants for diffusion from brain to blood of gray and white matter were 0.021 and 0.0016 min-1, respectively. The values of CBF obtained by applying a microsphere model to the data acquired from 0 to 3.2 min after IMP injection were overestimated by approximately 23% compared with those values obtained using a nonmicrosphere model. This is considered to be due to the effect of the IMP activity in the vascular space. Values obtained using the data acquired from 3.2 to 6.4 min were underestimated by approximately 15%. When the values of CBF obtained by a microsphere model were interpolated, they became nearly equal to those obtained using a nonmicrosphere model at about 4 to 5 min after injection. This is suggested to be the reason why the underestimation due to diffusion from brain to blood is cancelled out by the overestimation due to the IMP in the vascular space. Our preliminary results suggest that it is necessary to take the diffusion of IMP from brain tissue to blood into account for the quantification of CBF using IMP.