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.

Mirtogenol® supplementation in association with dorzolamide-timolol or latanoprost improves the retinal microcirculation in asymptomatic patients with increased ocular pressure.

OBJECTIVE: Supplementation with Mirtogenol® improves the retinal microcirculation and reduces intraocular pressure (IOP) in ocular hypertension, when administrated either alone or in association with an ophthalmic solution (latanoprost). In this study, microcirculatory parameters (perfusion of the circle of Zinn-Haller and retinal circulation) and oxidative stress were tested to assess the effects of Mirtogenol® plus traditional antihypertensive drugs in patients with elevated IOP. PATIENTS AND METHODS: 88 otherwise healthy patients with increased IOP were followed-up in a supplement registry for 12 weeks. Three groups received; (a) dorzolamide-timolol plus Mirtogenol®; (b) latanoprost drops plus Mirtogenol® or (c) latanoprost only. Oral supplementation consisted of two tablets/day of Mirtogenol® (80 mg of bilberry extract, Mirtoselect® plus 40 mg of Pycnogenol®). IOP, retinal blood flow, perfusion of the circle of Zinn-Haller, and oxidative stress were measured during the registry period. RESULTS: The three study groups were comparable; IOP and ocular blood flow velocity at inclusion were also comparable. Over the study period the decrease in IOP and the improvements in retinal microcirculation were statistically significant for all management groups, with a marginally more evident benefit in Mirtogenol®+latanosprost-treated patients. At 12 weeks, the altered perfusion at the circle of Zinn-Haller was improved in all groups; patients using Mirtogenol® showed a better perfusional pattern compared with subjects using only latanoprost. A reduction in oxidative stress was observed in supplemented subjects at the end of the study period; no significant change was seen in non-supplemented patients. All managements were well-tolerated without side effects. CONCLUSIONS: Supplementation with Mirtogenol®, in addition to local ophthalmic treatments, is safe and may contribute as a supplementary management to reach a normal IOP and ocular microcirculatory parameters.

High-intensity focused ultrasound treatment in patients with refractory glaucoma.

PURPOSE: To assess the safety and efficacy of ultrasound coagulation of the ciliary body in refractory glaucoma. METHODS: This prospective multicenter interventional study was conducted in two Italian university-affiliated glaucoma centers: St. Orsola-Malpighi Teaching Hospital (Bologna, Italy) and University Eye Clinic of Genoa (Genoa, Italy). The main inclusion criterion was the diagnosis of glaucoma with a baseline intraocular pressure (IOP) ≥ 21 mmHg while on maximum topical and systemic medical hypotensive treatment. The EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France), which was employed in the study, uses miniaturized transducers to produce high-intensity focused ultrasound (HIFU). Treatment consisted of the sequential activation of each transducer lasting 4 s (group 1), 6 s (group 2) or 8 s (group 3). Hypotensive medications were interrupted after surgery and then prescribed only if postoperative IOP was ≥ 21 mmHg during follow-up visits. Patients were assessed before and 1, 7, 14, 30, 90 and 180 days after the procedure. Primary outcomes were the mean IOP reduction in the overall population and in groups 1, 2 and 3, and the rates of complete success, qualified success and failure. RESULTS: Thirty eyes (16 open-angle, 10 angle-closure and 4 neovascular glaucoma) of 30 patients were included. The mean preoperative IOP was 30.1 ± 10.5 mmHg. Twenty-nine patients completed the entire study follow-up; one patient exited from the study 3 months after HIFU and underwent trabeculectomy. At days 1 and 180, the mean IOP was significantly reduced (18.4 ± 7.2 and 20.2 ± 6.2 mmHg, respectively; all p < 0.0001). Group 3 patients (8-s ultrasound exposure time) showed a greater IOP reduction than the other two groups (-16.2 ± 8.3 for group 3 vs. -8.8 ± 6.6 for group 2 and -3.7 ± 6.5 for group 1; p = 0.02 and p < 0.001, respectively). Qualified and complete success was achieved in 23.3 and 46.7% of patients, respectively; treatment failure was recorded in 6.6%. CONCLUSIONS: Ultrasonic coagulation of the ciliary body is a safe and effective procedure for reducing IOP in refractory glaucoma. The increase in ultrasound exposure time appears to improve the response rate and the global efficacy of the procedure, with no detrimental effect on safety.

Bilberry extracts are not created equal: the role of non anthocyanin fraction. Discovering the "dark side of the force" in a preliminary study.

OBJECTIVE: Several experimental studies and clinical trials support the potential of bilberry (Vaccinium myrtillus L) extracts in promoting eye health and circulation. Many active ingredients have been isolated from the berries and leaves of the bilberry plant. However, anthocyanins represent the most widely studied bioactive compounds in this plant. PATIENTS AND METHODS: The aim of this registry, supplement study was to evaluate the effects of Mirtoselect® (standardized in 36% anthocyanins and obtained by an industrial extraction process that preserves the full range of the non-anthocyanin components, mainly natural sugars and polyphenols) in different types of retinal vasculopathies. In total, 140 patients with different types of retinopathy spontaneously decided to join one of the following groups: standard management (SM) only (n=38); SM associated with Mirtoselect® supplementation (n=47); SM associated with a generic bilberry extract supplementation (n=55). Retinal circulatory parameters and flow measurements of the retinal vessels were evaluated at the inclusion and after 6-months supplementation. RESULTS: Overall, significant improvements in several retinal circulatory parameters such as retinal blood flow velocity, with respect to the values at inclusion, were observed in both supplementation groups, especially in Mirtoselect® supplementation group. However, at 6 months, inter-group comparison revealed a statistical advantage in all tested parameters for Mirtoselect® supplementation groups. No side effects or tolerability concerns were reported. CONCLUSIONS: Our registry study suggests that Mirtoselect® supplementation could represent an effective and safe integrated approach for the treatment of different retinopathies.

Recurrence of retinal vein thrombosis with Pycnogenol® or Aspirin® supplementation: a registry study.

AIM: The aim of this study was to use Pycnogenol® to reduce the recurrence of retinal vein thrombosis (RVT) after a first episode. Pycnogenol® is an anti-inflammatory, anti-edema and an antiplatelet agent with a "mild" antithrombotic activity. The registry, using Pycnogenol® was aimed at reducing the number of repeated episodes of RVT. METHODS: Possible management options--chosen by patients--were: standard management; standard management + oral Aspirin® 100 mg once/day (if there were no tolerability problems before admission); standard management + Pycnogenol® two 50 mg capsules per day (for a total of 100 mg/day). Number of subjects, age, sex, distribution, percentage of smokers, and vision were comparable. RESULTS: Recurrent RVT was seen in 17.39% of controls and in 3.56% of subjects supplemented with Pycnogenol® (P<0.05 vs. controls). There was RVT in 15.38% of the subjects using Aspirin®. The incidence of RVT was 4.88 times higher with standard management in comparison with the supplement group and 4.32 lower with Pycnogenol® supplementation in comparison with Aspirin®. Vision level was better with Pycnogenol® (20/25 at nine months; P<0.05). With Pycnogenol®, edema at the retinal level was also significantly reduced compared to the other groups. Pycnogenol® has a very good safety profile. In the Aspirin® group 26 completed 9 months and 6 subjects dropped out for tolerability problems. In the Aspirin® group, 2 minor, subclinical, retinal, hemorrhagic episodes during the follow-up were observed (2 subjects out of 26, equivalent to 7.69%). This pilot registry indicates that Pycnogenol® seems to reduce the recurrence of RVT without side effects. It does not induce new hemorrhagic episodes that may be theoretically linked to the use of Aspirin® (or other antiplatelets). CONCLUSION: Larger studies should be planned involving a wider range of conditions, diseases and risk factors associated to RVT and to its recurrence.

Weaning of infants from non invasive ventilation.

Non invasive ventilation (NIV) is commonly used to treat RDS in preterm infants. Although less risky than invasive ventilation, NIV has some potential side effects and appropriate weaning is therefore desirable. However, criteria for the definition of stability prior to attempting NIV weaning as well as the best weaning strategies need to be more investigated. The aim of this review is to identify criteria and interventions that can facilitate correct weaning from NIV.

Flow-synchronized nasal intermittent positive pressure ventilation for infants <32 weeks' gestation with respiratory distress syndrome.

Aim. To evaluate whether synchronized-NIPPV (SNIPPV) used after the INSURE procedure can reduce mechanical ventilation (MV) need in preterm infants with RDS more effectively than NCPAP and to compare the clinical course and the incidence of short-term outcomes of infants managed with SNIPPV or NCPAP. Methods. Chart data of inborn infants <32 weeks undergoing INSURE approach in the period January 2009-December 2010 were reviewed. After INSURE, newborns born January -December 2009 received NCPAP, whereas those born January-December 2010 received SNIPPV. INSURE failure was defined as FiO(2) need >0.4, respiratory acidosis, or intractable apnoea that occurred within 72 hours of surfactant administration. Results. Eleven out of 31 (35.5%) infants in the NCPAP group and 2 out of 33 (6.1%) infants in the SNIPPV group failed the INSURE approach and underwent MV (P < 0.004). Fewer infants in the INSURE/SNIPPV group needed a second dose of surfactant, a high caffeine maintenance dose, and pharmacological treatment for PDA. Differences in O(2) dependency at 28 days and 36 weeks of postmenstrual age were at the limit of significance in favor of SNIPPV treated infants. Conclusions. SNIPPV use after INSURE technique in our NICU reduced MV need and favorably affected short-term morbidities of our premature infants.

Surfactant and non invasive ventilation for preterm infants.

Mechanical ventilation, although life-saving, predisposes preterm infants to BPD. NCPAP emerged as an alternative to invasive ventilation, but it fails in about 30% of infants even when coupled with surfactant therapy. Alternative modes of non invasive ventilation are currently used in neonatology in order to prevent mechanical ventilation. Among these, Synchronized Nasal Intermittent Positive Ventilation (SNIPPV) seems to ensure better results. (www.actabiomedica.it).

Pulmonary ultrasonography in the follow-up of respiratory distress syndrome on preterm newborns. Reduction of X-ray exposure.

PURPOSE: Respiratory distress syndrome (RDS) is the most common cause of respiratory failure in preterm neonates, whose lungs are often immature. The diagnosis and follow-up are based on clinical and radiographic findings. Due to the problem of air artifacts, ultrasonography (US) is not used routinely in the diagnosis of lung diseases. However, when the alveolar air content decreases, as it does in RDS, characteristic patterns appear that can be observed during US lung examinations. The aim of this study was to determine whether the use of chest radiographs in neonates with RDS could be reduced by the routine use of chest US for follow-up examinations. MATERIALS AND METHODS: From April through September 2008, were enrolled all preterm newborns, with very low birth weight (VLBW), consecutive admitted in NICU with clinically and radiologically diagnosed RDS. We performed lung ultrasound examination in this patients. Video-taped US examinations were done every 8-12 h until clinical resolution of the disease was observed. Chest X-rays were performed only in unclear cases. We compared the number of chest radiographs obtained in the NICU during this period and during the preceding six months. RESULTS: 105 serial US lung examinations were performed in 21 preterm infant with clinically and radiologically diagnosed RDS. US lung examinations revealed "comet-tail" artifacts that were compact, diffuse, and symmetrically distributed throughout both lung fields. In 8 cases, the pleural line was also extensively thickened and irregular, and in 7 cases multiple subpleural hypoechoic areas indicative of lung consolidation were observed (mainly on posterior and lateral scans). The mean number of chest radiographs per infant performed in the NICU during the study period was significantly lower than that of the preceding six months (2.6 ± 1 versus 3.8 ± 1.5; p < 0.05). CONCLUSIONS: Chest ultrasound is a valid alternative for the follow-up of VLBW infants with RDS, which can decrease the need for chest X-rays and reduce patient exposure to ionizing radiation.

[Introduction to the principles of neonatal resuscitation]. / Introduzione ai principi della rianimazione neonatale.

WHO has estimated that as many as 10% of all newborn infants need some intervention at birth and approximately 1% more extensive intervention. If this is correct, up to 13-14 million of the world's annual newborn infants need intervention and of these approximately 1.5 million will need intensive therapy. Each year at least 1.16 million newborn babies die in sub-Saharan Africa. This region has the highest risk of newborn deaths and the slowest progress in reducing mortality. The transition from intrauterine to extrauterine life is extremely hazardous, with probably more radical physiologic adjustments required during and immediately following the birth process than at any other point in a human lifetime. Although certain episodes of fetal asphyxia cannot be prevented a prompt and skilled resuscitation may prevent lifelong adverse sequelae. Optimal resuscitation procedures should therefore become high priority. The ILCOR, the AHA and the AAP have established their new guidelines for newborn resuscitation on review of the evidence for each step. There still are a number of unanswered questions regarding newborn resuscitation (the ideal ratio of chest compressions to ventilation, the benefits and risks of supplementary oxygen, the indications for volume therapy, the optimal glucose level in infants that required resuscitation, the better ventilation in a newborn at birth.

Electro-optic properties of switchable gratings made of polymer and nematic liquid-crystal slices.

We report the diffraction properties at wavelengths of 632.8 and 1550 nm for volume transmission gratings made of a sequence of continuously aligned nematic liquid-crystal layers separated by isotropic polymer slices. The gratings are generated by holographically curing a solution of liquid crystal diluted in an isotropic prepolymer by means of a laser beam at a wavelength of 352 nm with a total intensity of approximately 10 mW/cm2. A diffraction efficiency of 98% was measured, and an electric field as low as 5 V/microm switches off the phase grating. Measured angular spectra are fitted by use of the modified coupled-mode theory including the effects of grating birefringence.

Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants.

In this study we hypothesized that nasal synchronized intermittent positive pressure ventilation (nSIPPV) would provide more ventilatory support than nasal continuous positive airway pressure (nCPAP) in the immediate post-extubation period in very low birth weight (VLBW) infants. We tested this hypothesis by comparing the effects of these two ventilatory techniques on ventilation, gas exchange, and patient inspiratory effort in 11 preterm infants immediately after extubation. All neonates studied (BW: 1141+/-(SEM) 53 g; GA: 28.1+/-(SEM) 0.5 wks) had received mechanical ventilation because of respiratory distress at birth and were extubated by day 14 of life. Nasal SIPPV and nCPAP were applied in random order to each infant after extubation so that each was his/her own control. Both nCPAP and nSIPPV were delivered at end-expiratory pressures (PEEP) of 3 cm H2O. Inspiratory times (Ti) and peak inspiratory pressures set during nSIPPV were the same as those used at the time of extubation. Recordings lasted 45 min in each mode of ventilation. Tidal volume (Vt), minute volume (Ve), respiratory rate (RR), airway pressure (Paw), transcutaneous PO2 (TcPO2) and PCO2 (TcPCO2) as well as phasic esophageal pressure deflections (Pe), as an estimate of inspiratory effort, were measured. The measurements obtained during both modes of ventilation indicated significant differences between the two techniques. Indeed, application of nSIPPV was associated with a statistically significant increase in Vt and Ve. In addition, Pe decreased by 30% during nSIPPV (P<0.01). TcPCO2 was statistically significantly lower during nSIPPV than nCPAP, and RR as well. These data therefore suggest that nSIPPV may provide more ventilatory support than nCPAP in the post-extubation period with less patient inspiratory effort.

Measurement of erythropoietin in chloroleukemic rats.

Erythropoietin (Ep) levels were measured in Shay chloroleukemic rats at various stages of anemia. Serum Ep was shown to increase logarithmically as the anemia became more severe. This increase in Ep levels was similar to that observed in normal rats subjected to acute blood loss. Significant levels of Ep were also demonstrated in ascitic fluid extracted from the peritoneal cavity of leukemic rats. These results indicate that the anemia of this disease is not due to a diminished production of Ep.