Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Espressione di Lectine, Miracoline e Chitinasi in seguito all'infezione da Tetranychus urticae in Citrus clementina.

La crescita delle piante è fortemente influenzata dalle condizioni ambientali ed in particolare dagli stress. I fattori di stress sono molteplici ed a seconda dell’intensità riducono la vitalità delle piante causando danni metabolici che possono riflettersi, in ambito agricolo, in un decremento della produttività. Le piante, essendo organismi sessili, non hanno la possibilità di sfuggire a tali stress, pertanto hanno sviluppato, nel corso dell’evoluzione, meccanismi molecolari che permettono di adattarsi a fattori ambientali sfavorevoli. Le barriere di difesa, utilizzate dalle piante per difendersi, possono essere passive o precostituite oppure attive o post-infettive. In particolar modo, nella difesa attiva, si mette in moto una serie di eventi metabolici che modificano lo stato fisiologico della pianta e la rendono più predisposta a far fronte agli “invasori”. Nelle piante si può parlare di diverse classi di risposte attive di difesa quali la HR (risposta ipersensitiva), la IR (resistenza indotta) e la SAR (resistenza sistemica acquisita). Perché il meccanismo di difesa si metta in moto, deve però avvenire il riconoscimento da parte della pianta dell’agente patogeno. Le sostanze chimiche riconosciute dalla pianta e che ne inducono le reazioni di difesa, vengono chiamate induttori o elicitori e promuovono in essa meccanismi di difesa in grado di proteggerla dagli attacchi di microrganismi patogeni. Inoltre, tali induttori sono in grado di agire anche in assenza dell’agente patogeno. Gli induttori vengono chiamati «esogeni» quando sono prodotti dagli agenti patogeni ed «endogeni» quando sono prodotti dalla pianta stessa, spesso in seguito alla degradazione della parete cellulare da parte dell’agente patogeno. Tra le molecole chimiche che giocano un ruolo fondamentale nel meccanismo di segnalazione delle cellule vegetali vi sono l’acido salicilico e l’acido jasmonico. L’acido jasmonico è uno dei più importanti e studiati fra gli elicitori che modulano le risposte della pianta verso gli stress biotici. Questo composto viene metabolizzato in molti derivati biologicamente attivi fra i quali il metil-jasmonato. Scopo di questa tesi è stato quello di valutare i meccanismi di risposta, a livello molecolare, indotti dall’attacco dell’acaride patogeno Tetranychus urticae (Koch) in una varietà di agrumi: il Citrus clementina (Hort. ex Tan). Il frutto di C. clementina, ampiamente coltivato nel bacino del Mediterraneo, è suscettibile all’attacco di un gran numero di insetti e patogeni, tra questi il polifago “spider mite” T. urticae risulta essere uno dei più distruttivi e resistenti agli acaricidi. Per questo motivo, è necessario conoscere le basi molecolari della risposta del C. clementina ai patogeni per poter selezionare degli ibridi resistenti all’attacco del T.urticae con un notevole vantaggio sia economico che ambientale. Tuttavia, i dati inerenti la risposta immunitaria del C. clementina allo stress indotto da T. urticae in letteratura sono limitati. In questo studio, utilizzando tecniche di biologia molecolare è stata valutata, nelle foglie di C.Clementina, l’espressione di tre geni che codificano per le proteine Lectina, Miracolina e Chitinasi che sembrano rivestire un ruolo nella risposta ai patogeni nelle piante. Dai risultati ottenuti dall’infezione delle piante con il polifago T.urticae, è stata evidenziata un’over-espressione dei relativi trascritti. Successivamente è stata caratterizzata la cinetica di induzione dei trascritti simulando l’attacco del T.urticae con l’elicitore metil-jasmonato (MeJA), che sembra giocare un ruolo dominante nella regolazione globale dell’espressione dei geni in risposta ai patogeni. Abbiamo riscontrato un incremento di espressione nel tempo dalle 2 ore alle 78 ore. E’ possibile quindi concludere che l’espressione di tali proteine e’ da considerarsi marker di infezione precoce. In particolare i nostri risultati hanno messo in evidenza che durante la risposta al trattamento con MeJA, oltre all’amplificato atteso della chitinasi, si ha la comparsa di un frammento più lungo. Nel tentativo di capire la sua funzione abbiamo osservato una stretta relazione con l’evoluzione dell’infezione. È pertanto necessario approfondire tale meccanismo allo scopo di poter considerare la comparsa della forma più lunga come indicatore di attacco patogeno in corso

A Stress responsive alternative splicing mechanism in <i>Citrus clementina</i> leaves

Chitinases are often considered pathogenesis-related proteins since their activity can be induced by viral infections, fungal and bacterial cell wall components, and also by more general sources of stress such as wounding, salicylic acid, ethylene, auxins and cytokinins. In the present study, comparative proteomic analysis showed the defense-related acidic chitinase II to be specifically induced in Citrus clementina leaves infested by the two-spotted spider mite Tetranychus urticae or treated with MeJA. In parallel, changes in the mRNA profiles of two partially homologous chitinase forms were shown by RT-PCR. In particular, the appearance of an additional cDNA chitinase fragment in T. urticae-infested and MeJA-treated leaves was observed. This finding may indicate a specific regulatory mechanism of chitinase expression. We report evidence for alternative splicing in T. urticae-infested C. clementina, where a premature stop codon after the first 135 amino acids was introduced. We observed inducible chitinase activity after MeJA treatment, indicative of a rapid plant response to infestation. This work provides the first evidence of chitinase alternative splicing in C. clementina. In addition, the presence of the dual-band pattern for chitinase cDNA by RT-PCR may represent a suitable predictive marker for early diagnosis of plant biotic stress

The importance of head and neck counselling in the COVID-19 era

L’importanza del “counselling” nei tumori testa-collo nell’era COVID-19

Multicenter comparative multimodality surveillance of women at genetic-familial high risk for breast cancer (HIBCRIT Study): Interim results

PURPOSE: To prospectively compare clinical breast examination (CBE), mammography, ultrasonography (US), and contrast material-enhanced magnetic resonance (MR) imaging for screening women at genetic-familial high risk for breast cancer and report interim results, with pathologic findings as standard. MATERIALS AND METHODS: Institutional review board of each center approved the research; informed written consent was obtained. CBE, mammography, US, and MR imaging were performed for yearly screening of BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or women enrolled because of a strong family history of breast or ovarian cancer (three or more events in first- or second-degree relatives in either maternal or paternal line; these included breast cancer in women younger than 60 years, ovarian cancer at any age, and male breast cancer at any age). RESULTS: Two hundred seventy-eight women (mean age, 46 years +/- 12 [standard deviation]) were enrolled. Breast cancer was found in 11 of 278 women at first round and seven of 99 at second round (14 invasive, four intraductal; eight were <or=10 mm in diameter). Detection rate per year was 4.8% (18 of 377) overall; 4.3% (11 of 258) in BRCA1 or BRCA2 mutation carriers and first-degree relatives of BRCA1 or BRCA2 mutation carriers versus 5.9% (seven of 119) in women enrolled because of strong family history; and 5.3% (nine of 169) in women with previous personal breast and/or ovarian cancer versus 4.3% (nine of 208) in those without. In six (33%) of 18 patients, cancer was detected only with MR imaging. Sensitivity was as follows: CBE, 50% (95% confidence interval [CI]: 29%, 71%); mammography, 59% (95% CI: 36%, 78%); US, 65% (95% CI: 41%, 83%); and MR imaging, 94% (95% CI: 82%, 99%). Positive predictive value was as follows: CBE, 82% (95% CI: 52%, 95%); mammography, 77% (95% CI: 50%, 92%); US, 65% (95% CI: 41%, 83%); and MR imaging, 63% (95% CI: 43%, 79%). CONCLUSION: Addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers

Survey of neonatal respiratory care and surfactant administration in very preterm infants in the Italian neonatal network

Introduction: Variation of respiratory care is described between centers around the world.The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. Methods:We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. Results: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. Conclusions. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement. © Mattioli 1885

Survey of neonatal respiratory care and surfactant administration in very preterm infants in the Italian neonatal network

Introduction: Variation of respiratory care is described between centers around the world.The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. Methods:We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. Results: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. Conclusions. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement. \ua9 Mattioli 1885

Association of maternal hypertension and chorioamnionitis with preterm outcomes

OBJECTIVES: We compared the relative effect of hypertensive disorders of pregnancy and chorioamnionitis on adverse neonatal outcomes in very preterm neonates, and studied whether gestational age (GA) modulates these effects. METHODS: A cohort of neonates 23 to 30 weeks' GA, born in 2008 to 2011 in 82 hospitals adhering to the Italian Neonatal Network, was analyzed. Infants born from mothers who had hypertensive disorders (N = 2096) were compared with those born after chorioamnionitis (N = 1510). Statistical analysis employed logistic models, adjusting for GA, hospital, and potential confounders. RESULTS: Overall mortality was higher after hypertension than after chorioamnionitis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.08-1.80), but this relationship changed across GA weeks; the OR for hypertension was highest at low GA, whereas from 28 weeks' GA onward, mortality was higher for chorioamnionitis. For other outcomes, the relative risks were constant across GA; infants born after hypertension had an increased risk for bronchopulmonary dysplasia (OR, 2.20; 95% CI, 1.68-2.88) and severe retinopathy of prematurity (OR, 1.48; 95% CI, 1.02-2.15), whereas there was a lower risk for early-onset sepsis (OR, 0.25; 95% CI, 0.19-0.34), severe intraventricular hemorrhage (OR, 0.65; 95% CI, 0.48-0.88), periventricular leukomalacia (OR, 0.70; 95% CI, 0.48-1.01), and surgical necrotizing enterocolitis or gastrointestinal perforation (OR, 0.47; 95% CI, 0.31-0.72). CONCLUSIONS: Mortality and other adverse outcomes in very preterm infants depend on antecedents of preterm birth. Hypertension and chorioamnionitis are associated with different patterns of outcomes; for mortality, the effect changes across GA weeks. Copyright \uc2\ua9 2014 by the American Academy of Pediatrics