Case Report of a Massive Life-threatening Neonatal Thrombosis Treated With a Targeted, Goal-oriented Scheme of Urokinase.

BACKGROUND: Thrombotic events are severe, often under-diagnosed, complications occurring in newborn infants during their hospital stay. Currently, there is no consensus regarding the optimal treatment scheme for thrombolysis in neonates. OBSERVATIONS: We present the case of a newborn suffering from a life-threatening thrombosis. Diagnosis was suggested by a gradual increase of C-reactive protein, with repeatedly normal procalcitonin. Thrombosis was successfully and safely treated with a long scheme of 21 days of urokinase, supported by vascular ultrasound and d-dimer trend. CONCLUSIONS: Laboratory and ultrasound results may help in adjusting the duration of the thrombolytic treatment, allowing for longer therapeutic schemes that could optimize treatment success. In addition, our case may suggest a possible combined role of C-reactive protein and procalcitonin as an early diagnostic aid in neonatal thrombosis.

The effect of clamped and unclamped umbilical cord samples on blood gas analysis.

PURPOSE: Delayed cord clamping for at least 60 s is recommended to improve neonatal outcomes. The aim of this study is to evaluate whether there are differences in cord BGA between samples collected after double clamping the cord or without clamping the cord, when blood collection occurs within 60 s from birth in both groups. METHODS: A cross-sectional study was carried out, collecting data from 6884 high-risk women who were divided into two groups based on the method of cord sampling (clamped vs unclamped). RESULTS: There were significant decrease in pH and BE values into unclamped group compared with the clamped group. This difference remained significant when considering pathological blood gas analysis parameters, with a higher percentage of pathological pH or BE values in the unclamped group. CONCLUSION: Samples from the unclamped cord alter the acid-base parameters compared to collection from the clamped cord; however, this difference does not appear to be of clinical relevance. Findings could be due to the large sample size, which allowed to achieve a high power and to investigate very small numerical changes between groups, leading to a statistically significant difference in pH and BE between samples even when we could not appreciate any clinical relevant difference of pH or BE between groups. When blood gas analysis is indicated, the priority should be given to the timing of blood collection to allow reliable results, to assess newborns status at birth and intervene when needed.

Use of Cardio-Pulmonary Ultrasound in the Neonatal Intensive Care Unit.

Cardiopulmonary ultrasound (CPUS), the combination of lung ultrasound (LUS) and targeted neonatal echocardiography (TnECHO)AA, may offer a more appropriate approach to the challenging neonatal cardiovascular and respiratory disorders. This paper reviews the possible use of CPUS in the neonatal intensive care unit (NICU).

Transcatheter closure in preterm infants with patent ductus arteriosus: feasibility, results, hemodynamic monitoring and future prospectives.

Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional closure is needed, it can be achieved with either surgical ligation or a catheter-based approach.Transcatheter PDA closure is among the safest of interventional cardiac procedures and it is the first choice for ductal closure in adults, children, and infants weighing more than 6 kg. In preterm and very low birth weight infants, it is increasingly becoming a valid and safe alternative to ligation, especially for the high success rate and the minor invasiveness and side effects. Nevertheless, being it performed at increasingly lower weights and gestational ages, hemodynamic complications are possible events to be foreseen.Procedural steps, timing, results, possible complications and available monitoring systems, as well as future outlooks are here discussed.

Lung ultrasound guided pulmonary recruitment during mechanical ventilation in neonates: A case series.

BACKGROUND: Recently, the first report of lung ultrasound (LUS) guided recruitment during open lung ventilation in neonates has been published. LUS guided recruitment can change the approach to open lung ventilation, which is currently performed without any measure of lung function/lung expansion in the neonatal population. METHODS: We included all the newborn infants that underwent a LUS-guided recruitment maneuver during mechanical ventilation as a rescue attempt for an extremely severe respiratory condition with oxygen saturation/fraction of inspired oxygen (SpO2/FIO2) ratio below 130 or the inability to wean off mechanical ventilation. RESULTS: We report a case series describing 4 LUS guided recruitment maneuvers, underlying crucial aspects of this technique that can improve the effectiveness of the procedure. In particular, we describe a novel pattern (the S-pattern) that allows us to distinguish the recruitable from the unrecruitable lung and guide the pressure titration phase. Additionally, we describe the optimal LUS-guided patient positioning. CONCLUSIONS: We believe that the inclusion of specifications regarding patient positioning and the S-pattern in the LUS-guided protocol may be beneficial for the success of the procedure.

Lung UltraSound Targeted Recruitment (LUSTR): A Novel Protocol to Optimize Open Lung Ventilation in Critically Ill Neonates.

This study investigated the effectiveness of an original Lung UltraSound Targeted Recruitment (LUSTR) protocol to improve the success of lung recruitment maneuvers (LRMs), which are performed as a rescue approach in critically ill neonates. All the LUSTR maneuvers, performed on infants with an oxygen saturation/fraction of inspired oxygen (S/F) ratio below 200, were included in this case-control study (LUSTR-group). The LUSTR-group was matched by the initial S/F ratio and underlying respiratory disease with a control group of lung recruitments performed following the standard oxygenation-guided procedure (Ox-group). The primary outcome was the improvement of the S/F ratio (Delta S/F) throughout the LRM. Secondary outcomes included the rate of air leaks. Each group was comprised of fourteen LRMs. As compared to the standard approach, the LUSTR protocol was associated with a higher success of the procedure in terms of Delta S/F (110 ± 47.3 vs. 64.1 ± 54.6, p = 0.02). This result remained significant after adjusting for confounding variables through multiple linear regressions. The incidence of pneumothorax was lower, although not reaching statistical significance, in the LUSTR-group (0 vs. 14.3%, p = 0.15). The LUSTR protocol may be a more effective and safer option than the oxygenation-based procedure to guide open lung ventilation in neonates, potentially improving ventilation and reducing the impact of ventilator-induced lung injury.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial.

BACKGROUND: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). METHODS: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. FINDINGS: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). INTERPRETATION: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. FUNDING: None.

[The surgical and endovascular treatment of the hepatic artery aneurysms: personal experience]. / Il trattamento chirurgico ed endovascolare degll' aneurismi dell'arteria epatica. Esperienza personale.

OBJECTIVE: The aim of this single-institution retrospective study is to report the results of surgical and endovascular treatment of hepatic artery aneurysms. MATERIALS AND METHODS: Twenty patients with an extraparenchimal hepatic artery aneurysm made part of the study In the first period, between February 1980 and December 1996, 12 patients were admitted and treated surgically. In the second period, January 1997 until December 2005, 8 patients were admitted. Four were treated surgically and 4 with an endovascular procedure. The aneurysms ranged from 2.3 cm to 6.2 cm Seventeen patients were asymptomatic, while three were symptomatic for pain and obstructive icterus. In 13 patients aneurysmectomy and graft interposition was performed, in three patients aneurysmectomy with dacron patch interposition was performed, and in 4 patients the aneurysm was excluded with a stent-graft. RESULTS: No perioperative mortality was noted and no major complication occurred. All endovascular procedures successfully excluded the aneurysm without signs of endoleak. Follow-up in 4 months, 6 months and 10 months postoperatively showed patency of the stent-graft with no signs of migration or endoleak. Only in one case, in the 8th post-operative month, thrombosis of the stent-graft occurred and the patient was completely asymptomatic. CONCLUSION: The natural history of hepatic artery aneurysms is rupture, and consequently there is an indication of treatment. Actually, we consider endovascular treatment as the first-choice-treatment whenever possible. Endovascularlly treated patients need a strict follow-up surveillance by imaging means. Particular attention so be given in the preoperative study of the collateral circulation in patient treated surgically.

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.

Bronchopulmonary Dysplasia and Chronic Lung Disease: Stem Cell Therapy.

Bronchopulmonary dysplasia (BPD), a major complication of premature birth, still lacks safe and effective treatment. Mesenchymal stem cells (MSCs) have been proven to ameliorate critical aspects of the BPD pathogenesis. MSCs seem to exert therapeutic effects through the paracrine secretion of anti-inflammatory, antioxidant, antiapoptotic, trophic, and proangiogenic factors. Although these findings are promising, understanding the mechanism of action of MSCs and MSC manufacturing is still evolving. Several aspects can affect the efficacy of MSC therapy. Further research is required to optimize this potentially game-changing treatment but the translation of regenerative cell therapies for patients has begun.

Patent ductus arteriosus: wait and see?

"Patent ductus arteriosus is one of most common problems that physicians caring for preterm infants have to face. Although medical and surgical treatment of PDA has been extensively investigated, results from the randomized controlled trials and metanalysis are still inconclusive and many authors therefore suggest a less aggressive attitude toward PDA. In the present review evidence for and against routine treatment of PDA are analyzed. A strict selection of those patients who are most likely to benefit from treatment is probably an appropriate strategy at this time but further studies, mainly targeted to long term outcomes, are needed to provide definitive indications."