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Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes., Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units., Design, Setting, and Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024., Intervention: Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up., Main Outcomes and Measures: The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA., Results: A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups., Conclusions and Relevance: In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

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., (© 2024. The Author(s).)

Objective. To describe the case of a large cervical mass diagnosed in the late third trimester with development of Kasabach-Merritt phenomenon (KMP) in the immediate postnatal period, along with a literature review. Methods . Description of case-report and literature search through Medline/Pubmed, performed from inception to December 2022 for articles relating to the pre and postnatal diagnosis of KMP. Results. A 36-year-old multiparous woman was admitted to hospital for contractions at 40 weeks of gestation, in an otherwise uneventful pregnancy. Admission's ultrasound showed the presence of a voluminous mass of 14x15 cm of the posterior side of the neck, highly vascularized, and no signs of hemodynamic imbalance. Postnatally, blood tests showed the presence of severe anemia and thrombocytopenia requiring several transfusions of blood, plasma, platelets and clotting factors. Due to the association of congenital hemangioma and thrombocytopenia a diagnosis of KMP was made. After attempts of conservative treatment, surgical removal was needed to stop the hematological cascade with regression of symptoms. The review of the literature identified 14 articles including 9 cases of prenatally suspected KMP and 6 diagnosed in the immediate postnatal period and without signs of fetal hydrops. Adverse perinatal outcome, in terms of postnatal death/termination of pregnancy, was observed in 67% of cases (6/9) in the prenatally suspected group and 33% of cases in those with a postnatal diagnosis of KMP. Fetal hydrops was present in 83% of cases with adverse perinatal outcome. Conclusions. The Kasabach-Merrit syndrome is a rare condition, which can have a dangerous evolution when it develops in utero or in the immediate postnatal period carrying a risk of perinatal mortality of approximately 50%. Even if the fetus shows no signs of anemia or heart failure, the risk of developing it in the immediate postnatal period is high and should be mentioned to the couple.

Introduction: Following the concerning levels of spread and severity of the infection, on 11 March 2020, the World Health Organisation declared the COVID-19 outbreak a pandemic. In response to the pandemic, governments adopted several mitigation strategies. The pandemic posed a great threat to the Italian healthcare workforce (HW), with Italy being one of the hardest-hit countries. The aim of this study is to estimate the economic burden of COVID-19 on the workforce of a teaching hospital in Central Italy. Two periods are compared: 1 March 2020-9 February 2021 vs. 10 February 2021-31 March 2022. Methods: This study is conducted from a societal perspective. The database ( n = 3298) of COVID-19-confirmed cases among the HW was obtained from the occupational health office of the hospital. The first entry on the database refers to 1 March 2020. Cost data were used to assess the economic burden of COVID-19 on the hospital workforce. They include two main groups: hourly salaries and medical expenses. The cost of productivity loss, hospital admission, at-home treatments, and contact tracing and screening tests were computed for the first and second periods of the analysis. Results: The total economic burden during the first period is estimated to be around EUR 3.8 million and in the second period EUR 4 million. However, the average cost per person is smaller in the second period (EUR 1561.78) compared to the first one (EUR 5906). In both periods, the cost of productivity loss is the largest component of the economic burden (55% and 57%). The cost of hospital admission decreased by more than 60% in the second period. Conclusion: Outcomes of the analysis suggest that the economic burden of COVID-19 on the HW is higher in the first period of analysis compared to the second period. The main reason could be identified in the shift from more severe and critical confirmed cases to more asymptomatic, mild, and moderate cases. The causes of this shift are not easily detectable. Vaccination, variants of the virus, and an individual's determinants of health could all be causes of the decrease in the economic burden of COVID-19 on the HW. COVID-19 can generate a high economic burden on healthcare workers and, more generally, on HWs. However, a comprehensive estimate of the economic burden of the pandemic needs to integrate the mental health repercussions and the long-term COVID-19 that will become evident in the coming years.

The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO 2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices.    Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: • Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. • Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: • Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. • Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The purpose of the present observational multicentric prospective study was to evaluate the efficacy and safety of a new infiltration device (CHondroGrid, Bioteck S.p.A, Arcugnano, Italy) based on hydrolyzed collagen in the treatment of rotator cuff tendinopathy., Methods: Seventy-one patients (53.3 ± 11.6 years old) affected by rotator cuff tendinopathy were treated in 2021 with two subacromial injections of CHondroGrid at 13 ± 2.9 days apart. The outcomes measured were the visual analog scale (VAS) score (in movement, during the night, and at rest), the Constant Score, the Simple Shoulder Test, and patient satisfaction. The outcome variables were measured before each injection, at 1 month and at 6 months after the last injection., Results: The treatment was significantly effective from the first injection and up to the six-month follow-up. At the last follow-up, the VAS score on movement had improved by 71% ( P  < .001), while the VAS score at rest and during the night had ameliorated by 91% and 87%, respectively ( P  < .001). The Constant Score and Simple Shoulder Test improved by 32% and 61%, respectively ( P  < .001). No adverse events were reported., Conclusions: CHondroGrid resulted in a safe and effective treatment in pain relief and for the functional recovery of rotator cuff tendinopathy., (© 2023 The Author(s).)

Clouds cover substantial parts of the Earth's surface and they are one of the most essential components of the global climate system impacting the Earth's radiation balance as well as the water cycle redistributing water around the globe as precipitation. Therefore, continuous observation of clouds is of primary interest in climate and hydrological studies. This work documents the first efforts in Italy in remote sensing clouds and precipitation using a combination of K- and W-band (24 and 94 GHz, respectively) radar profilers. Such a dual-frequency radar configuration has not been widely used yet, but it could catch on in the near future given its lower initial cost and ease of deployment for commercially available systems at 24 GHz, with respect to more established configurations. A field campaign running at the Casale Calore observatory at the University of L'Aquila, Italy, nestled in the Apennine mountain range is described. The campaign features are preceded by a review of the literature and the underpinning theoretical background that might help newcomers, especially in the Italian community, to approach cloud and precipitation remote sensing. This activity takes place in interesting time for radar sensing clouds and precipitation, stimulated both by the launch of the ESA/JAXA EarthCARE satellite missions scheduled in 2024, which will have on-board, among other instruments, a W-band Doppler cloud radar and the proposal of new missions using cloud radars currently undergoing their feasibility studies (e.g., WIVERN and AOS in Europe and Canada, and U.S., respectively).

Background: Providing appropriate care at birth remains a crucial strategy for reducing neonatal mortality and morbidity. We aimed to evaluate the consistency of practice and the adherence to the international guidelines on neonatal resuscitation in level-I and level-II Italian birth hospitals., Methods: This was a cross-sectional electronic survey. A 91-item questionnaire focusing on current delivery room practices in neonatal resuscitation was sent to the directors of 418 Italian neonatal facilities., Results: The response rate was 61.7% (258/418), comprising 95.6% (110/115) from level-II and 49.0% (148/303) from level-I centres. In 2018, approximately 300,000 births occurred at the participating hospitals, with a median of 1664 births/centre in level-II and 737 births/centre in level-I hospitals. Participating level-II hospitals provided nasal-CPAP and/or high-flow nasal cannulae (100%), mechanical ventilation (99.1%), HFOV (71.0%), inhaled nitric oxide (80.0%), therapeutic hypothermia (76.4%), and extracorporeal membrane oxygenation ECMO (8.2%). Nasal-CPAP and/or high-flow nasal cannulae and mechanical ventilation were available in 77.7 and 21.6% of the level-I centres, respectively. Multidisciplinary antenatal counselling was routinely offered to parents at 90.0% (90) of level-II hospitals, and 57.4% (85) of level-I hospitals (p < 0.001). Laryngeal masks were available in more than 90% of participating hospitals while an end-tidal CO 2 detector was available in only 20%. Significant differences between level-II and level-I centres were found in the composition of resuscitation teams for high-risk deliveries, team briefings before resuscitation, providers qualified with full resuscitation skills, self-confidence, and use of sodium bicarbonate., Conclusions: This survey provides insight into neonatal resuscitation practices in a large sample of Italian hospitals. Overall, adherence to international guidelines on neonatal resuscitation was high, but differences in practice between the participating centres and the guidelines exist. Clinicians and stakeholders should consider this information when allocating resources and planning perinatal programs in Italy., (© 2022. The Author(s).)

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life., (© 2022. The Author(s).)

Background: We aimed to evaluate the policies and practices about neonatal resuscitation in a large sample of European hospitals., Methods: This was a cross-sectional electronic survey. A 91-item questionnaire focusing on the current delivery room practices in neonatal resuscitation domains was individually sent to the directors of 730 European neonatal facilities or (in 5 countries) made available as a Web-based link. A comparison was made between hospitals with ≤2,000 and those with >2,000 births/year and between hospitals in 5 European areas (Eastern Europe, Italy, Mediterranean countries, Turkey, and Western Europe)., Results: The response rate was 57% and included participants from 33 European countries. In 2018, approximately 1.27 million births occurred at the participating hospitals, with a median of 1,900 births/center (interquartile range: 1,400-3,000). Routine antenatal counseling (p < 0.05), the presence of a resuscitation team at all deliveries (p < 0.01), umbilical cord management (p < 0.01), practices for thermal management (p < 0.05), and heart rate monitoring (p < 0.01) were significantly different between hospitals with ≤2,000 births/year and those with >2,000 births/year. Ethical and educational aspects were similar between hospitals with low and high birth volumes. Significant variance in practice, ethical decision-making, and training programs were found between hospitals in 5 different European areas., Conclusions: Several recommendations about available equipment and clinical practices recommended by the international guidelines are already implemented by centers in Europe, but a large variance still persists. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs., (© 2022 S. Karger AG, Basel.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To examine the relationship between electrographic seizures and developmental outcome at 18 and 24 months in neonates with moderate and severe hypoxic-ischemic encephalopathy [HIE] treated with therapeutic hypothermia [TH]., Study Design: 30 term infants with moderate-severe HIE treated with TH were enrolled prospectively from June 2012 to May 2018. All had continuous single channel amplitude integrated EEG (aEEG) monitoring for a minimum of 72 h and brain MR within 4 weeks. The aEEG was classified by severity of background and seizure burden. MR images were graded by the severity of injury. Outcome (defined abnormal in case of death, dyskinetic or spastic quadriplegic cerebral palsy, epilepsy, or Bayley III score < 85 in all three subscales or < 70 in any individual subscale) was assessed at 18 and 24 months., Results: Seizures were recorded in 24 out of 30 [80 %] neonates and an abnormal outcome was observed in 7 [23 %] of infants. Patients with poor outcome had a statistically significant correlation with: high seizure burden (p = 0.0004), need for more than one antiepileptic drugs (p = 0.006), a persistent abnormal aEEG trace at 48 h (p = 0.0001) and moderate-severe brain injury at MRI (p = 0.0001). Moreover, infants with status epilepticus or frequent seizures reported a significantly association with abnormal MR imaging and poor outcome than patients with sporadic seizures (p = 0.0009)., Conclusion: The role of seizures in the pathogenesis of brain injury remains controversial. In our cohort the presence of seizures, per se, was not associated with abnormal outcome; however a high seizure burden as well as a persistent abnormal aEEG background pattern and MR lesions resulted significantly associated with poor prognosis., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Neonatal incubators are important tools for sick newborns in the first few days of life. Nevertheless, their electric engine, often very close to the newborn's body, emits electromagnetic fields (EMF) to which newborns are exposed. Aim of this paper is to review the available literature on EMF exposure in incubators, and the effects of such exposures on newborns that have been investigated., Methods: We carried out a systematic review of studies about EMF emissions produced by incubators, using Medline and Embase databases from 1993 to 2017., Results: We retrieved 15 papers that described the EMF exposure in incubators and their biological effects on babies. EMF levels in incubators appear to be between 2 and 100 mG, depending on the distance of the mattress from the electric engine. In some cases, they exceed this range. These values interfere with melatonin production or with vagal tone. Even caregivers are exposed to high EMF, above 200 mG, when working at close contact with the incubators., Conclusion: EMF have been described as potentially hazardous for human health, and values reported in this review are an alert to prevent babies' and caregivers' exposure when close to the incubators. A precautionary approach should be adopted in future incubator design, to prevent high exposures of newborns in incubators and of caregivers as well.

Objective: In the recent years the increase of methamphetamines (MTA) abusers women has become an emerging problem. Very little data has been published regarding the effects of prenatal MTA exposure. We describe a case of MTA related toxicity in a term newborn which have early onset of neonatal encephalopathy and liver failure., Case Report: A term infant born to a MTA abuser mother developed seizures and severe neurological symptoms shortly after birth. Methamphetamine was detected both in maternal and in neonatal urine. The laboratoristic tests revealed severe hepatic insufficiency, coagulopathy and thrombocytopenia. Due to neonatal encephalopathy the newborn underwent hypothermia. Phenobarbital, fresh frozen plasma, platelet transfusions and vitamin K were administered. Cranial ultrasonography and magnetic resonance imaging (MRI) showed diffuse white matter damage and two ischemic-hemorrhagic cerebral lesions. Gradually the clinical conditions improved, at 1 month MRI showed a stabilization of cerebral lesions with residual diffuse leukomalacia. Physiotherapy and neurological follow up is ongoing to evaluate the long term effects., Conclusions: although infrequent, MTA-related toxicity should be suspected in infants with neurologic and hepatic symptoms. Further studies are warranted to confirm our findings in order to identify newborns at high risk of acute MTA toxicity in time to provide them the appropriate support., (Copyright © 2018. Published by Elsevier B.V.)

The first case of severe drug-induced gastrointestinal injury related to levodopa is described. The 86-year-old patient experienced acute colitis temporally related to the intake of the drug with complete resolution of symptoms on levodopa withdrawal. Awareness of the possibility of a levodopa-related damage on colon biopsies performed for acute colitis is of paramount importance for pathologists. However, in order to exclude or confirm a drug-related damage an effective communications between clinicians and pathologists is always required., (Copyright © 2018 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Background: Different surgical approaches are currently available to treat knee chondral defects. Microfracture is the most commonly applied, but it often leads to a mechanically inferior fibrocartilaginous tissue. To overcome this shortcoming, the Autologous, Matrix-Induced Chondrogenesis (AMIC) technique has been proposed. To further enhance the outcome of AMIC, the addition of haemoderivatives containing growth factors that stimulate cartilage healing has emerged as a new treatment method. Recently, a novel leucocyte-platelet-concentrated membrane (CLP-MB), highly enriched in platelets, monocytes/macrophages, fibrinogen, CD34 + and CD34 + VEGFR-2 + CD133 + cells, has been developed. Additionally, an injectable collagen scaffold (Cartifill) has been proposed as a replacement of the AMIC standard collagen membrane., Aims: This preliminary study is aimed to evaluate the short-term safety and efficacy of the use of the CLP-MB membrane and injectable collagen scaffold when combined in single-step AMIC procedures for the treatment of knee chondral lesions., Methods: Medical records of patients who underwent an AMIC procedure with the CLP-MB membrane combined with Cartifill were reviewed retrospectively. Follow-up assessments were conducted at 6 and 12 months after surgery. Clinical function was assessed on the basis of the International Knee Documentation Committee (IKDC) score. Pain was evaluated using the visual analogue scale (VAS)., Results: Twenty-five patients were identified as meeting the inclusion criteria. Mean IKDC and VAS scores significantly improved during the follow-up time. The postoperative course was uneventful., Conclusions: AMIC combined with the CLP-MB membrane, and Cartifill seems to be a promising approach to treat knee chondral defects.

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.

Objective: International Guidelines provide a standardised approach to newborn resuscitation in the DR and, in their most recent versions, recommendations dedicated to management of ELBWI were progressively increased. It is expected that introduction in clinical practice and dissemination of the most recent evidence should be more consistent in academic than in non-academic hospitals. The aim of the study was to compare adherence to the International Guidelines and consistency of practice in delivery room management of extremely low birth weight infants between academic and non-academic institutions., Methods: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012., Results: There was a 92% (n = 98/107) response rate. Apart from polyethylene wrapping to optimise thermal control, perinatal management approach was comparable between academic and non-academic centres., Conclusions: There were minor differences in management of extremely low birth weight infants between Italian academic and non-academic institutions, apart from thermal management. Although there was a good, overall adherence to the International Guidelines for Neonatal Resuscitation, temperature management was not in accordance with official recommendations and every effort has to be done to improve this aspect.

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

The occurrence of 45 PCBs was studied in a wastewater treatment plant (WWTP), which treats industrial wastewater from the zone of Porto Marghera (Venice, Italy) in an MBR, and in the Naviglio del Brenta River, which serves as a source of process water supply for this industrial zone. The focus of the study was placed on the comparison of levels of contamination of the WWTP effluent and the river water by selected PCBs in order to understand the major source of PCB pollution for the Lagoon of Venice and contrast them with the current legislation. Out of 45, 31 PCBs were detected in the WWTP at total median PCB concentration of 5.5 ng/L with a predominant presence of six indicator - PCBs (PCB 28, 52, 101, 138, 153 and 180), which accounted for 50-55% of total PCBs in both wastewater and sludge samples. The total PCB concentration was reduced by around 90% during the applied wastewater treatment to a median concentration of 0.5 ng/L at the WWTP effluent. In the samples collected from the river, 27 PCBs were detected at total median concentration of 2.1 ng/L, which is few times higher than the total PCB concentration found in the WWTP effluent. This result suggests that the current legislative limitations applied to the WWTPs effluent discharges into the Lagoon of Venice, regarding the presence of PCBs (i.e. absent) is rather arbitrary given the higher concentration levels encountered in river water than in the WWTP effluent of the studied industrial WWTP., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Phototherapy is standard care for treatment of neonatal hyperbilirubinemia. Our aim was to compare the effectiveness of broad-spectrum light (BSL) to that of blue light emitting diodes (LED) phototherapy for the treatment of jaundiced late preterm and term infants. Infants with gestational age from 35(+0) to 41(+6) weeks of gestation and nonhemolytic hyperbilirubinemia were randomized to treatment with BSL phototherapy or blue LED phototherapy. A total of 20 infants were included in the blue LED phototherapy group and 20 in the BSL phototherapy group. The duration of phototherapy was lower in the BSL than in the blue LED phototherapy group (15.8 ± 4.9 vs. 20.6 ± 6.0 hours; p = 0.009), and infants in the former group had a lower probability (p = 0.015) of remaining in phototherapy than infants in the latter. We concluded that BSL phototherapy is more effective than blue LED phototherapy for the treatment of hyperbilirubinemia in late preterm and term infants. Our data suggest that these results are not due to the different irradiance of the two phototherapy systems, but probably depend on their different peak light emissions., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

In this article we evaluated the consistency of practice and the adherence to the International Guidelines in early delivery room management of ELBW infants in Italy. A polyethylene bag/wrap was used by 54 centres (55.1%). In Northern regions, one centre (2.5%) reported to use oxygen concentrations &gt;40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was widely used (77/97, 79.4%). A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy. Forty-seven out of 98 (47.9%) centres declared to administer prophylactic surfactant in delivery room. Although there were geographic differences in the country, our results showed a good general adherence to the International Guidelines for Neonatal Resuscitation.

This study critically evaluates the biological processes and techniques applied to remove nitrogen and phosphorus from the anaerobic supernatant produced from the treatment of the organic fraction of municipal solid waste (OFMSW) and from its co-digestion with other biodegradable organic waste (BOW) streams. The wide application of anaerobic digestion for the treatment of several organic waste streams results in the production of high quantities of anaerobic effluents. Such effluents are characterized by high nutrient content, because organic and particulate nitrogen and phosphorus are hydrolyzed in the anaerobic digestion process. Consequently, adequate post-treatment is required in order to comply with the existing land application and discharge legislation in the European Union countries. This may include physicochemical and biological processes, with the latter being more advantageous due to their lower cost. Nitrogen removal is accomplished through the conventional nitrification/denitrification, nitritation/denitritation and the complete autotrophic nitrogen removal process; the latter is accomplished by nitritation coupled with the anoxic ammonium oxidation process. As anaerobic digestion effluents are characterized by low COD/TKN ratio, conventional denitrification/nitrification is not an attractive option; short-cut nitrogen removal processes are more promising. Both suspended and attached growth processes have been employed to treat the anaerobic supernatant. Specifically, the sequencing batch reactor, the membrane bioreactor, the conventional activated sludge and the moving bed biofilm reactor processes have been investigated. Physicochemical phosphorus removal via struvite precipitation has been extensively examined. Enhanced biological phosphorus removal from the anaerobic supernatant can take place through the sequencing anaerobic/aerobic process. More recently, denitrifying phosphorus removal via nitrite or nitrate has been explored. The removal of phosphorus from the anaerobic supernatant of OFMSW is an interesting research topic that has not yet been explored. At the moment, standardization in the design of facilities that treat anaerobic supernatant produced from the treatment of OFMSW is still under development. To move toward this direction, it is first necessary to assess the performance of alternative treatment options. It study concentrates existing data regarding the characteristics of the anaerobic supernatant produced from the treatment of OFMSW and from their co-digestion with other BOW. This provides data documenting the effect of the anaerobic digestion operating conditions on the supernatant quality and critically evaluates alternative options for the post-treatment of the liquid fraction produced from the anaerobic digestion process.

Aim: To identify changes in practice between two historical periods (2002 vs. 2011) in early delivery room (DR) management of ELBWI in Italian tertiary centres., Methods: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. The same questionnaire was used in a national survey conducted in 2002. Among the participating centres, those that filled the questionnaire in both study periods were selected for inclusion in this study., Results: There was an 88% (n=76/86) and 92% (n=98/107) response rate in the 2 surveys, respectively. The two groups overlapped for 64 centres. During the study period, the use of polyethylene bags/wraps increased from 4.7% to 59.4% of the centres. The units using 100% oxygen concentrations to initiate resuscitation of ELBWI decreased from 56.2% to 6.2%. The approach to respiratory management was changed for the majority of the examined issues: positive pressure ventilation (PPV) administered through a T-piece resuscitator (from 14.0% to 85.9%); use of PEEP during PPV (from 35.9% to 95.3%); use of CPAP (from 43.1% to 86.2%). From 2002 to 2011, the percentages of ELBWI intubated in DR decreased in favor of those managed with N-CPAP; ELBWI receiving chest compressions and medications at birth were clinically comparable., Conclusions: During the two study periods, the approach to the ELBWI at birth significantly changed. More attention was devoted to temperature control, use of oxygen, and less-invasive respiratory support. Nevertheless, some relevant interventions were not uniformly followed by the surveyed centres., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aim: To evaluate any geographical variations in practice and adherence to international guidelines for early delivery room management of extremely low birthweight (ELBW) infants in the North, Centre and South of Italy., Methods: A questionnaire was sent to all 107 directors of Italian level III centres between April and August 2012., Results: There was a 92% (n = 98) response rate. A polyethylene bag/wrap was used by 54 centres (55.1%), with the highest rate in Northern Italy (77.5%) and the lowest rate in Southern (37.7%) areas. In Northern regions, one centre (2.5%) said it used oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was more frequently available in the Northern (95%) units than in those in the Central (66.7%) and Southern (69.4%) regions. A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy: 5%, 18% and 22% in Northern, Central and Southern units, respectively., Conclusion: In Italy, delivery room management of ELBW infants showed marked geographical variations. Implementation of national training programmes could increase adherence to the guidelines and reduce such discordance., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Pulmonary pneumatoceles are thin-walled, air-filled cysts that develop within the lung parenchyma. Most often, they occur as a sequel of acute pneumonia, commonly caused by Staphylococcus aureus in children. Limited data are available about infective pulmonary cysts in newborns. We report a case of a newborn, who developed multiple pneumatoceles after Escherichia coli pneumonia., (© 2013 Wiley Periodicals, Inc.)

The ideal treatment for displaced intraarticular calcaneal fractures is still under debate. Open reduction and internal fixation is the most popular surgical procedure; however, wound complications, hardware failure and infection remain a major concern. The aim of this study was to evaluate the results of a new minimally-invasive surgical procedure: closed reduction technique combined with balloon-assisted fracture augmentation with cement or calcium phosphate (minimally-invasive percutaneous calcaneoplasty). We retrospectively reviewed 11 patients that sustained Sander's type II and III calcaneal fractures treated in our institution from January 2008 to June 2010. The same approach and technique was utilized in all cases. Conventional X-rays and CT scan have been performed pre- and post-operatively. The average follow-up was 24 months. The American Orthopaedic Foot and Ankle Society ankle/hindfoot score has been utilized for clinical evaluation and Bohler's angle to assess bone reduction. All cases obtained bony union in 2/3 months, with average Bohler's angle of 22.97° (from 14.21° to 32.83°). No skin complications or adverse reactions were observed, with only one patient complaining of residual pain in the hindfoot. Minimally-invasive percutaneous calcaneoplasty can represent an alternative to open reduction internal fixation in the treatment of calcaneal fractures, allowing stable reduction without plating, early function recovery and short hospital stay.

The start-up of the completely autotrophic nitrogen removal process was examined in a sequencing batch reactor (SBR) using low activity anoxic ammonium oxidation (anammox) inoculum. The SBR received effluent from an upflow anaerobic sludge blanket (UASB) that treated low strength wastewater. The volumetric nitrogen loading rate (vNLR) was first 0.24 ± 0.11 kg Nm(-3)d(-1) and then reduced to 0.10 ± 0.02 kg Nm(-3)d(-1). The average specific anammox activity was 2.27 ± 1.31 mg N (gVSS h)(-1), at 30°C representing an increase of 161% compared to the inoculum. The decrease in vNLR did not significantly affect anammox activity, but resulted in a decrease of denitrifying heterotrophic activity to very low levels after the first 30 days owing to the decrease of organic loading rate (OLR). Fluorescence in situ hybridization (FISH) analysis confirmed the stable presence of anammox bacteria in biomass. Numerous filamentous microorganisms were present, several of which were in a state of endogenous respiration., (Copyright © 2013. Published by Elsevier Ltd.)

Objective: To investigate the effects of elective primary and elective repeat caesarean deliveries on lactation at hospital discharge., Design: Cohort study., Setting: Four Italian teaching hospitals - Padua, Brescia, L'Aquila and Udine., Interventions: Deliveries were classified as vaginal, elective caesarean (primary and repeat) or emergency caesarean. A total of 2296 (24.7%) infants born by caesarean section (CS), 816 of which (35.5%) classified as primary elective CS and 796 (34.7%) as repeat elective CS, were studied. Moreover, 30.2% of the elective CS deliveries took place before 39 weeks., Main Outcome Measures: Feeding modalities at discharge: formula, complementary and breastfeeding., Results: At discharge, 6.9% of the vaginal delivery mothers, 8.3% of the emergency CS mothers, 18.6% of the elective CS mothers, 23.3% of the primary CS mothers and 13.9% of the repeat CS mothers were using infant formula exclusively. Multivariate analysis (OR; 95% CI) identified primary elective delivery (3.74; 3.0 to 4.60), lower gestational age (1.16; 1.10 to 1.23), and place L'Aquila versus Udine (1.42; 1.01 to 2.09) and of Brescia versus Udine hospitals (6.16; 4.53 to 8.37) as independent predictors of formula feeding at discharge., Conclusions: These findings provide new information about the risks of breastfeeding failure connected to elective CS delivery, particularly if primary and scheduled before 39 weeks of gestation.

Oxygen has been widely used in neonatal resuscitation for about 300 years. In October 2010, the International Liaison Committee on Neonatal Resuscitation released new guidelines. Based on experimental studies and randomized clinical trials, the recommendations on evaluation and monitoring of oxygenation status and oxygen supplementation in the delivery room were revised in detail. They include: inaccuracy of oxygenation clinical assessment (colour), mandatory use of pulse oximeter, specific saturation targets and oxygen concentrations during positive pressure ventilation in preterm and term infants. In this review, we describe oxygen management in the delivery room in terms of clinical assessment, monitoring, treatment and the gap of knowledge.

The occurrence and removal of 42 pharmaceuticals, belonging to different therapeutic groups (analgesics and anti-inflammatory drugs, anti-ulcer agent, psychiatric drugs, antiepileptic drug, antibiotics, ß-blockers, diuretics, lipid regulator and cholesterol lowering statin drugs and anti-histamines), were studied in the wastewater and sewage sludge trains of a full scale integrated treatment plant. The plant employs a biological nutrient removal (BNR) process for the treatment of municipal wastewater, and a single-stage mesophilic anaerobic co-digestion for the treatment of wasted activated sludge mixed with the organic fraction of municipal solid waste (OFMSW), followed by a short-cut nitrification-denitrification of the anaerobic supernatant in a sequential batch reactor. Influent and effluent wastewater, as well as thickened, digested and treated sludge were sampled and analyzed for the selected pharmaceuticals in order to study their presence and fate during the treatment. Twenty three compounds were detected in influent and effluent wastewater and eleven in sludge. Infiltration of groundwater in the sewer system led to a dilution of raw sewage, resulting in lower concentrations in wastewater (up to 0.7 μg/L in influent) and sludge (70 ng/g d.w.). Due to the dilution, overall risk quotient for the mixture of pharmaceuticals detected in effluent wastewater was less than one, indicating no direct risk for the aquatic environment. A wide range of removal efficiencies during the treatment was observed, i.e. <20% to 90%. The influent concentrations of the target pharmaceuticals, as polar compounds, were undoubtedly mostly affected by BNR process in the wastewater train, and less by anaerobic-co-digestion. Mass balance calculations showed that less than 2% of the total mass load of the studied pharmaceuticals was removed by sorption. Experimentally estimated distribution coefficients (<500 L/kg) also indicated that the selected pharmaceuticals preferably remain in the aqueous phase, and that biodegradation/transformation is the primary removal mechanism for these compounds during wastewater treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

During the last few decades, neonatal survival rates for preterm infants have markedly been improved. The American Academy of Pediatrics recommended that preterm neonates should receive sufficient nutrients to enable them to grow at a rate similar to that of fetuses of the same gestational age. Although human milk is the recommended nutritional source for newborn infants for at least the first six months of postnatal life, unfortified human breast milk may not meet the recommended nutritional needs of growing preterm infants. Human milk must therefore be supplemented (fortified) with the nutrients in short supply. The fortification of human milk can be implemented in two different forms: standard and individualized. The new concepts and recommendations for optimization of human milk fortification is the "individualized fortification". Actually, two methods have been proposed for individualization: the "targeted/tailored fortification" and the "adjustable fortification". In summary, the use of fortified human milk produces adequate growth in premature infants and satisfies the specific nutritional requirements of these infants. The use of individualized fortification is recommended.

We studied the occurrence, removal, and fate of 16 polycyclic aromatic hydrocarbons (PAHs) and 23 volatile organic compounds (VOCs) in Italian municipal wastewater treatment systems in terms of their common contents and forms, and their apparent and actual removal in both conventional activated-sludge processes (CASP) and membrane bioreactors (MBRs). We studied five representative full-scale CASP treatment plants (design capacities of 12,000 to 700,000 population-equivalent), three of which included MBR systems (one full-scale and two pilot-scale) operating in parallel with the conventional systems. We studied the solid-liquid partitioning and fates of these substances using both conventional samples and a novel membrane-equipped automatic sampler. Among the VOCs, toluene, ethylbenzene, xylenes, styrene, 1,2,4-trimethylbenzene, and 4-chlorotoluene were ubiquitous, whereas naphthalene, acenaphthene, fluorene, and phenanthrene were the most common PAHs. Both PAHs and aromatic VOCs had removal efficiencies of 40-60% in the headworks, even in plants without primary sedimentation. Mainly due to volatilization, aromatic VOCs had comparable removal efficiencies in CASP and MBRs, even for different sludge ages. MBRs did not enhance the retention of PAHs sorbed to suspended particulates compared with CASPs. On the other hand, the specific daily accumulation of PAHs in the MBR's activated sludge decreased logarithmically with increasing sludge age, indicating enhanced biodegradation of PAHs. The PAH and aromatic VOC contents in the final effluent are not a major driver for widespread municipal adoption of MBRs, but MBRs may enhance the biodegradation of PAHs and their removal from the environment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The Mediterranean Region is a semi-arid area whose land is facing serious erosion, causing adverse impacts on agriculture. To improve the water availability, researchers have proposed the reclamation and reuse of treated wastewater. In this paper, we report the main findings of 10 years of research on the efficiencies of a conventional activated sludge process and a submerged membrane bioreactor, with particular emphasis on the removal of non-conventional pollutants. The studies showed that the membrane bioreactor produced a virtually solids-free, high-quality permeate: most nutrients, heavy metals, and persistent organic pollutants were removed, and in particular, dioxins, furans, and polychlorinated biphenyls were typically present at concentrations below the detection limit. Moreover, the total coliforms count decreased by 4-5 log and Escherichia coli was absent from the membrane bioreactor permeate. These results, combined with the continuing reduction of the capital and operating costs for this approach, suggest that membrane bioreactors are an increasingly cost-effective technology to produce treated effluents that are suitable for reuse., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Proximal tibial fractures are difficult lesions to treat because of the involvement of the articular surface, the often occurring comminution, and the precarious condition of the soft tissues, especially following high-energy trauma. Aim of the treatment is to restore the congruence of the articular surface supporting the tibial plateau cartilage which is usually depressed; to fix the fracture with a stable device; to allow early rehabilitation. We present our treatment strategy, utilising closed or open reduction and internal fixation, angle-stable polyaxial plates, immediate osteointegration, when necessary, with autologous bone graft or other osteoconductive material augmented with autologous platelet gel. Surgery is soft-tissue dependent in terms of timing, and it is usually performed directly or under supervision of an experienced surgeon utilising, whenever possible, a tissue sparing technique. A cohort of 58 proximal tibial fractures, surgically treated, from January 2004 to June 2007, was retrospectively reviewed. Fractures were classified according the OTA/AO classification. The assessment of the functional outcome with the use of the Rasmussen score identified good to excellent results in 78% of the cohort 12 months post-surgery. Internal fixation with locking plates, following the principles of MIPO (Minimally Invasive Percutaneous Osteosynthesis), provides satisfactory fracture reduction with good results regarding the mid-term clinical outcome., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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.

Hypertension is one of the world's largest public health problems and it is both a disease and a risk factor for cardiovascular disease (CVD). The heart, the endothelium and the kidneys are the target organs of hypertension. Recently, several antihypertensive drugs have been introduced to the market; therefore, the choice is mainly determined by the patients' features. In particular, ACE inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) demonstrate a larger reduction in cardiovascular risk than other antihypertensive treatments because of the existence of blood pressure-independent effects. In fact, the angiotensin II pathway plays a major role in metabolic, haemodynamic and endothelial homeostasis. For these reasons, ACE inhibitors and ARBs have primary indications in patients with obesity, hypercholesterolaemia and diabetes mellitus because of their favourable metabolic properties. Furthermore, several large trials have demonstrated that they have favourable effects also in patients with left ventricular dysfunction or systolic heart failure, as well as other forms of heart disease. Drugs affecting the angiotensin II pathway may reduce endothelial dysfunction through several mechanisms including reduction of vascular permeability and oxidative stress. Another important effect of these drugs is neuroprotection. This is an important effect because in the near future, due to an aging population, an important goal for optimal antihypertensive treatment will be the prevention of cognitive decline. ACE inhibitors and ARBs are very important drugs in the modern management of the total cardiovascular risk in hypertensive patients.

The European Commission (EC) has strong commitments and recognises the need to continue to ensure that HIV/AIDS research efforts receive global attention. The EC is facing this challenge in a global context and has made substantial investments together with European Developing Countries Clinical Trial Partnership (EDCTP) to formulate a program for the accomplishment of a scientific strategic plan promoting the European/African HIV vaccine development approach. The EC and EDCTP has convened a number of meetings by experts in basic and clinical virology, immunology, epidemiology, as well as industrial and regulatory representatives. The remit of the committee of experts was to define (1) objective criteria for selection of HIV candidates; (2) to determine criteria for selection of sites for clinical trials in Europe and Africa. The resulting consensus paper will guide the EC and EDCTP in developing HIV vaccine strategy and recommendations.

Flow cytometric analysis was used in this study to characterize the lymphocyte population present in the vaginal mucosa of the cynomolgus monkey. Vaginal immune cells were obtained, using absorbent wicks, from 11 normal cycling female monkeys at different stages of the menstrual cycle and from three nursing monkeys (not cycling). Leucocytes, including lymphocytes and monocyte-macrophage cells, were present in the cervicovaginal secretions of healthy cynomolgous primates throughout the three phases of the menstrual cycle. We also found that even if immune cells were constant throughout the menstrual cycle, among the T cell subsets there were differences. CD8+ cells [14.5+/-9% (mean+/-S.D.); range 3-30%] were more numerous compared to the mean number of CD4+ cells [7.3+/-5% (mean+/-S.D.); range 2-15%]. Characterization of the vaginal cells during the nursing period showed that the monocyte-macrophage (CD14+, CD11c+) cells were abundant compared with the low number of both B (CD20+) and T cells (CD2+). Our results show that cytometric analysis by FACS can be used to identify the immune cell populations present at the local level. This technique may provide a useful tool by which the vaginal environment can be studied in order to correlate cell phenotype with immune function.

Objective: The development of drugs that can be used as topical microbicides is currently recognized as a priority area of research., Design: A preclinical evaluation of the potential effectiveness of TMC120, a non-nucleoside reverse transcriptase inhibitor (NNRTI), as a topical microbicide to prevent vaginal HIV-1 transmission in a humanized severe combined immunodeficient (hu-SCID) mouse model., Methods: Reconstituted mice received an intravaginal application of a TMC120-containing gel 20 min prior to a non-invasive vaginal challenge with cell-associated HIV. The possible cytotoxic effect of TMC120-containing-gel on lymphocytes was assessed and their in vivo migration was followed using fluorescently labelled human lymphocytes. Systemic infection was monitored by p24 antigen detection in culture supernatant from cocultured intraperitoneal cells using antigen capture enzyme-linked immunosorbent assay test and by the presence of integrated proviral HIV-1 DNA in DNA extracted from spleen cells. In vivo migration of labelled lymphocytes was examined by analysis of cells isolated from regional lymph nodes., Results: In this model, systemic infection was successfully inhibited by the presence of TMC120-containing gel at vaginal level. The in vivo migration of human lymphocytes from the vagina to regional lymph nodes, following the deposition of TMC120-containing gel, excluded the possibility that inhibition of systemic infection was a result of NNRTI toxicity., Conclusions: Vaginal transmission of HIV was successfully prevented by the application of a gel formulation containing TMC120. This is the first evidence of the in vivo effectiveness of a microbicide preparation containing an NNRTI against cell-associated HIV.

Objective: To develop an animal model of vaginal transmission of HIV-1 for the evaluation of vaginal microbicides., Design: Vaginal infection was performed in SCID mice reconstituted with 4 x 107 human peripheral blood lymphocytes (hu-PBL) by non-invasive vaginal administration. The hu-PBL were previously infected in vitro with a non-syncytium (NSI) strain of HIV-1 (SF162) (hu-PBL-SCID). Lymphocyte migration in vivo was examined using fluorescently labelled human lymphocytes., Methods: The percentage of CD4 T cells, plasma viral load and p24 antigen were evaluated using fluorescent activated cell sorting (FACS), the Amplicor HIV-1 monitor kit and enzyme-linked immunosorbent assay, respectively. Polymerase chain reaction (PCR) analysis was performed on DNA extracted from spleen and lymph nodes. For in vivo migration of labelled lymphocytes, the mice were sacrificed after 4, 24 and 48 h; vaginae and local lymph nodes were removed, snap frozen with OCT, sectioned and examined by fluorescent microscopy and FACS., Results: HIV transmission was established using virus-infected cells inoculated vaginally, as shown by FACS, HIV viral load, p24 and PCR results. Labelled cells were easily located within the vaginal tissues after 4 h. However, few or no cells could be identified after 24 or 48 h at the vaginal level, whereas labelled cells could be detected at the level of regional lymph nodes., Conclusions: Because of its simplicity and practical features compared with other animal models, the vaginal HIV-infected hu-SCID mouse model may prove useful to test the activity of compounds against cell-associated HIV and, possibly, other sexually transmitted diseases.

Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic immune responses. The distribution of T and B cell subsets, cytokine patterns, and antibody (Ab) isotype profiles were similar for adenoids and tonsils. Both tissues contained predominantly B cells ( approximately 65%), approximately 5% macrophages, and 30% CD3(+) T cells. The T cells were primarily of the CD4(+) subset ( approximately 80%). Tonsillar intraepithelial lymphocytes were also enriched in B cells. The analysis of dispersed cells revealed a higher frequency of cells secreting IgG than IgA and the predominant Ig subclass profiles were IgG1 > IgG3 and IgA1 > IgA2, respectively. In situ analysis also revealed higher numbers of IgG- than IgA-positive cells. These IgG-positive cells were present in the epithelium and in the subepithelial zones of both tonsils and adenoids. Mitogen-triggered T cells from tonsils and adenoids produced both Th1- and Th2-type cytokines, clearly exhibiting their pluripotentiality for support of cell-mediated and Ab responses. Interestingly, antigen-specific T cells produced interferon-gamma and lower levels of interleukin-5. These results suggest that adenoids and tonsils of the nasopharyngeal-associated lymphoreticular tissues represent a distinct component of the mucosal-associated lymphoreticular tissues with features of both systemic and mucosal compartments.

Objective: The aim of this study was to investigate susceptibility to spontaneous or anti-Fas-induced apoptosis in peripheral blood mononuclear cells (PBMC) from HIV-positive patients before and during highly active anti-retroviral therapy (HAART)., Design: A longitudinal study was performed on 12 evaluable patients on HAART. This cohort was analysed prior to and at week 2, 4, 8, 16 and 24 after beginning HAART. Variations in CD4 and CD8 cells, viral load, susceptibility to spontaneous or anti-Fas-induced apoptosis in the presence of IL-2, IL-4 or IL-12 were studied. Expression of Fas and Bcl-2 were also assessed., Methods: Levels of HIV RNA were determined by a quantitative reverse transcription-PCR assay. Apoptosis was evaluated by staining isolated nuclei with propidium iodide followed by multiparameter flow cytometry analysis., Results: Spontaneous apoptosis of PBMC was promptly inhibited after the start of treatment. Similarly, anti-Fas-induced apoptosis diminished greatly during treatment. Expression of Fas decreased significantly, while that of Bcl-2 remained statistically unchanged during the first 24 weeks of therapy. Levels of apoptosis correlated inversely to CD4 cell counts and directly to viral load in a highly significant way. Expression of Fas was directly correlated to apoptosis. Interleukin (IL)-2, but not IL-4 or IL-12, protected PBMC of HIV-positive individuals from spontaneous or anti-Fas-induced apoptosis before and during HAART., Conclusion: These results suggest that regulation of apoptosis and of Fas expression are involved in immunoreconstitution during HAART.

Design: Despite significant rises in total CD4 T cells, the process of immune reconstitution in adults with HIV infection treated with potent antiretroviral treatment results in a rather slow increase in phenotypically naive lymphocytes. In children more than in adults, thymic function may be at least partly restored when disease-induced immunosuppression is attenuated by pharmacological means., Methods: Twenty-five vertically infected and antiretroviral-experienced [zidovudine (ZDV)/ZDV plus didanosine (ddl)] children were prospectively followed during 12 months of treatment with lamivudine (3TC), stavudine (d4T) and indinavir (IDV). The plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined. The relationship between the degree of immune reconstitution and thymus volume assessed by nuclear magnetic resonance was also examined., Results: An early and steep increase in CD45RA+62L+ T cells was observed in parallel with a sustained decrease in plasma HIV RNA levels and a significant rise in total CD4 T cells. This increase was significantly greater than that observed in CD4+CD45RO+ T cells. Analysis of the CD4 T cell receptor (TCR) beta repertoire and T helper function showed the ability to reconstitute families almost completely absent at baseline, and a substantial improvement of antigen-specific responses by peripheral blood lymphocytes. The rise in CD4 cells and in CD4+CD45RA+62L+ T cells was statistically associated with changes in thymus size observed over time., Conclusion: These data suggest a relevant contribution of the thymus to reconstitution of the peripheral pool of T cells in vertically HIV-infected children treated with potent antiretroviral regimens.

The potential therapeutic utility of thalidomide (Thd), an effective inhibitor of tumor necrosis factor (TNF)-alpha in vitro, was investigated in cynomolgus monkeys (Macaca fascicularis) at 10 months after infection with simian immunodeficiency virus (SIV). Thd-treated macaques (n = 8) received an oral dose (10 mg) daily for 7 days, followed by a wash-out period of 5 weeks. A 2nd cycle of treatment was performed on the same animals at higher doses (20 mg Thd/day) for 14 days. The control monkeys (n = 7) received a placebo for the same period of time. In the present study, we show that Thd, in addition to inhibiting TNF-alpha production after in vitro mitogen stimulation of peripheral blood mononuclear cells (PBMCs), was able to restore the proliferative responses to SIV peptides in monkeys that were infected with SIV. Interestingly, we found that such effects are associated with an increased expression of CD28 cell surface receptors on CD4+ T-cells paralleled by a decrease on CD8+ T-cells. At the same time, significant reduction in either cell-associated viral load or plasma viral RNA was not observed among the SIV-infected monkeys during the two treatment cycles, when compared with the placebo group.

The infection of cynomolgus monkeys with an attenuated simian immunodeficiency virus (SIV) (C8) carrying a deletion in the nef gene results in a persistent infection associated with an extremely low viral burden in peripheral blood mononuclear cells. The aim of this study was to determine (1) the breadth of the protection after repeated challenges of monkeys with SIV homologous strains of different pathogenicity, (2) the genotypic stability of the live virus vaccine, (3) whether the protection might depend on cellular resistance to superinfection, and (4) whether immunogenic stimuli such as recall antigens could reactivate the replication of the C8 virus. To address these goals, the monkeys were challenged at 40 weeks after C8 infection with 50 MID50 of cloned SIVmac251, BK28 grown on macaque cells. They were protected as indicated by several criteria, including virus isolation, anamnestic serological responses, and viral diagnostic PCR. At 92 weeks after the first challenge, unfractionated peripheral blood mononuclear cells from protected monkeys were susceptible to the in vitro infection with SIVmac32H, spl. At 143 weeks after C8 infection, the four protected monkeys were rechallenged with 50 MID50 of the pathogenic SIVmac32H, spl grown on macaque cells. Once again, they were protected. The C8 virus remained genotypically stable, and depletion of CD4(+) cells was not observed during approximately 3 years of follow-up. In contrast, it was found that the infection with SIVmac32H, spl induced CD4(+) cell depletion in three of three control monkeys. Of importance, stimulation with tetanus toxoid, although capable of inducing specific humoral and T cell proliferative responses, failed to induce a detectable reactivation of C8 virus., (Copyright 1999 Academic Press.)

Cynomolgus monkeys (Macaca fascicularis) were immunized by intravaginal administration of live recombinant Streptococcus gordonii. The vaccine strains of S. gordonii expressed the V3 domain of the gpl20 of human immunodeficiency virus type 1 (HIV-1), and the E7 protein of human papillomavirus type 16 (HPV 16). Multiple inocula of recombinant bacteria were used, since S. gordonii could persist for no longer than 3 days in the monkey vagina. Vaginal immunization was found to induce a local and systemic immune response specific for the heterologous antigen expressed by the bacteria. This antigen-specific immune response consisted of vaginal IgA, serum IgG, and a T-cell proliferative response measured on PBMCs. Vaginal IgG and serum IgA were not detected.