Inspiratory-expiratory variation of pleural line thickness in neonates with and without acute respiratory failure.

BACKGROUND: There are relatively few data about the ultrasound evaluation of pleural line in patients with respiratory failure. We measured the pleural line thickness during different phases of the respiratory cycle in neonates with and without acute respiratory failure as we hypothesized that this can significantly change. METHODS: Prospective, observational, cohort study performed in an academic tertiary neonatal intensive care unit recruiting neonates with transient tachypnoea of the neonate (TTN), respiratory distress syndrome (RDS) or neonatal acute respiratory distress syndrome (NARDS). Neonates with no lung disease (NLD) were also recruited as controls. Pleural line thickness was measured with high-frequency ultrasound at end-inspiration and end-expiration by two different raters. RESULTS: Pleural line thickness was slightly but significantly higher at end-expiration (0.53 [0.43-0.63] mm) than at end-inspiration (0.5 [0.4-0.6] mm; p = 0.001) for the whole population. End-inspiratory (NLD: 0.45 [0.38-0.53], TTN: 0.49 [0.43-0.59], RDS: 0.53 [0.41-0.62], NARDS: 0.6 [0.5-0.7] mm) and -expiratory (NLD: 0.47 [0.42-0.56], TTN: 0.48 [0.43-0.61], RDS: 0.53 [0.46-0.65], NARDS: 0.61 [0.54-0.72] mm) thickness were significantly different (overall p = 0.021 for both), between the groups although the absolute differences were small. The inter-rater agreement was optimal (ICC: 0.95 (0.94-0.96)). Coefficient of variation was 2.8% and 2.5% for end-inspiratory and end-expiratory measurements, respectively. These findings provide normative data of pleural line thickness for the most common forms of neonatal acute respiratory failure and are useful to design future studies to investigate possible clinical applications.

Global and regional heterogeneity of lung aeration in neonates with different respiratory disorders: a physiological, observational study.

BACKGROUND.: Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). We hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support. METHODS.: Observational, prospective study. Neonates with respiratory distress syndrome (RDS), transient tachypnea (TTN), evolving bronchopulmonary dysplasia (BPD) and neonatal ARDS (NARDS) were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and inter-patient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes. RESULTS.: 230 (50 RDS, TTN or evolving BPD and 80 NARDS) patients were studied. Intra-patient aeration heterogeneity was higher in TTN (mean: 61% [standard deviation: 33%]) and evolving BPD (mean: 57% [standard deviation: 20%], p<0.001), with distinctive aeration distributions. Inter-patient aeration heterogeneity was high for all disorders (Gini-Simpson index: between 0.6 and 0.72) except RDS (Gini-Simpson index: 0.5) whose heterogeneity was significantly lower than all others (p<0.001). NARDS and evolving BPD had the most diffuse injury and worst gas exchange metrics. Regional aeration heterogeneity was mostly localized in upper anterior and posterior zones. Aeration heterogeneity and total lung aeration had an exponential relationship (p<0.001; adj-R 2=0.62). Aeration heterogeneity is associated with greater total lung aeration (i.e., higher heterogeneity means a relatively higher proportion of normally aerated lung zones, thus greater aeration; p<0.001; adj-R 2=0.83) and better oxygenation metrics upon multivariable analyses. CONCLUSIONS.: Global aeration heterogeneity and regional aeration heterogeneity differ amongst neonatal respiratory disorders. TTN and evolving BPD have the highest intra-patient aeration heterogeneity. TTN, evolving BPD and NARDS have the highest inter-patient aeration heterogeneity, but the latter two have the most diffuse injury and worst gas exchange. Higher aeration heterogeneity is associated with better total lung aeration and oxygenation.

Skin thickness in preterm neonates: relationship with skin bilirubin and predicted mortality.

This study investigates the relationship between the thickness of skin in preterm infants and its link with bilirubin and mortality, as this may help understanding the potential deleterious effects of phototherapy. Observational, prospective cohort study enrolling preterm neonates needing phototherapy and admitted to a neonatal intensive care unit. Transcutaneous bilirubin (TcB) and blood bilirubin were simultaneously measured before the onset of phototherapy, if any. The skin depth was measured by high-frequency point-of-care ultrasound. Mortality risk was estimated using the critical risk index for babies-II. Correlations and multivariate regressions (adjusting for several confounders) were applied to study the relationship between skin depth, TcB, and predicted mortality. One hundred fifty-nine neonates were studied. There was a positive and steady correlation between skin depth and TcB (r = 0.402 (95%CI: 0.206; 0.568), p < 0.001) and inverse correlation between skin depth and predicted mortality (r = -0.503 (95%CI: -0.61; -0.37), p < 0.001) as well as between TcB and predicted mortality (r = -0.303 (95%CI: -0.49; -0.09), p = 0.005). Multivariate analyses showed skin depth to be the strongest risk factors associated with both increasing TcB (ß = 198 (59;338), p < 0.001) and decreasing risk of death (ß = -24 (-46;2), p = 0.049). Blood bilirubin and gestational age were also associated with TcB and predicted mortality, respectively.   Conclusion: In NICU-admitted preterm infants, thicker skin is associated with higher TcB levels irrespective of gestational age. Greater skin depth is also associated with lower predicted mortality irrespective of blood bilirubin. What is Known: • In preterm infants, phototherapy may improve neuro-developmental outcomes but, particularly in the smallest and sickest ones, may increase mortality. • Mechanisms behind this effect are unclear but could involve the small thickness of preterm skin. This however has never been studied in relationship with bilirubin and mortality. What is New: • In NICU-admitted preterm infants, thicker skin is associated with higher levels of transcutaneous bilirubin, irrespective of gestational age and with lower predicted mortality, irrespective of blood bilirubin. • These data suggest that a thinner skin may contain less bilirubin to be photoisomerised and protect internal tissues less efficiently.

Evolution of Ultrasound-Assessed Lung Aeration and Gas Exchange in Respiratory Distress Syndrome and Transient Tachypnea of the Neonate.

OBJECTIVE: To use clinical, lung ultrasound, and gas exchange data to clarify the evolution of lung aeration and function in neonates with respiratory distress syndrome (RDS) and transient tachypnea of the neonate (TTN), the most common types of neonatal respiratory failure. STUDY DESIGN: In this prospective observational cohort study, lung aeration and function were measured with a semiquantitative lung ultrasound score (LUS) and transcutaneous blood gas measurement performed at 1 hour (time point 0), 6 hours (time point 1), 12 hours (time point 2), 24 hours (time point 3) and 72 hours (time point 4) of life. Endogenous surfactant was estimated using lamellar body count (LBC). LUS, oxygenation index (OI), oxygen saturation index (OSI), and transcutaneous pressure of carbon dioxide (PtcCO2) were the primary outcomes. All results were adjusted for gestational age. RESULTS: Sixty-nine neonates were enrolled in the RDS cohort, and 58 neonates were enrolled in the TTN cohort. LUS improved over time (within-subjects, P < .001) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001). Oxygenation improved over time (within-subjects, P = .011 for OI, P < .001 for OSI) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001 for OI and OSI). PtcCO2 improved over time (within-subjects, P < .001) and was similar in the RDS and TTN cohorts at all time points. Results were unchanged after adjustment for gestational age. LBC was associated with RDS (ß = -0.2 [95% CI, -0.004 to -0.0001]; P = .037) and LUS (ß = -3 [95% CI, -5.5 to -0.5]; P = .019). CONCLUSIONS: For the first 72 hours of life, the RDS cohort had worse lung aeration and oxygenation compared with the TTN cohort at all time points. CO2 clearance did not differ between the cohorts, whereas both lung aeration and function improved in the first 72 hours of life.

Continuous Venovenous Hemofiltration Performed by Neonatologists With Cardio-Renal Pediatric Dialysis Emergency Machine to Treat Fluid Overload During Multiple Organ Dysfunction Syndrome: A Case Series.

OBJECTIVES: A new device is available for neonates needing extracorporeal renal replacement therapy. We reviewed the use of this device (in continuous venovenous hemofiltration [CVVH] mode) in term or preterm neonates affected by multiple organ dysfunction syndrome (MODS) with fluid overload. DESIGN: Case series. SETTING: Academic specialized referral neonatal ICU (NICU) with expertise on advanced life support and monitoring. PATIENTS: Neonates with MODS and fluid overload despite conventional treatments and receiving at least one CVVH session. INTERVENTION: CVVH with the Cardio-Renal Pediatric Dialysis Emergency Machine. MEASUREMENTS AND MAIN RESULTS: Ten (three preterm) neonates were treated using 18 consecutive CVVH sessions. All patients were in life-threatening conditions and successfully completed the CVVH treatments, which almost always lasted 24 hr/session, without major side effects. Three neonates survived and were successfully discharged from hospital with normal follow-up. CVVH reduced fluid overload (before versus after represented as a weight percentage: 23.5% [12-34%] vs 14.6% [8.2-24.1%]; p = 0.006) and lactate (before versus after: 4.6 [2.9-12.1] vs 2.9 mmol/L [2.3-5.5 mmol/L]; p = 0.001). CVVH also improved the Pa o2 to Fio2 (before vs after: 188 mm Hg [118-253 mm Hg] vs 240 mm Hg [161-309 mm Hg]; p = 0.003) and oxygenation index (before vs after: 5.9 [3.8-14.6] vs 4 [2.9-11]; p = 0.002). The average cost of CVVH in these patients was minor (≈3%) in comparison with the median total cost of NICU care per patient. CONCLUSIONS: We have provided CVVH to critically ill term and preterm neonates with MODS. CVVH improved fluid overload and oxygenation. The cost of CVVH was minimal compared with the overall cost of neonatal intensive care.

Ultrasound-assessed lung aeration, oxygenation and respiratory care in neonatal bile acid pneumonia: A nested case-control study.

AIM: Neonatal bile acid pneumonia (NBAP) occurs in neonates following obstetric cholestasis. We aimed to study the lung aeration and respiratory support of NBAP. METHODS: Nested, case/control study enrolling age-matched neonates with NBAP, respiratory distress syndrome (RDS) or transient tachypnoea (TTN). Lung aeration and oxygenation were assessed with lung ultrasound score, oxygenation index and SpO2 /FiO2 . RESULTS: Nineteen, 22 and 25 neonates with NBAP, RDS and TTN, respectively were studied (mean gestational age = 33 (2.2) weeks, 30 (45.5%) males). Upon admission, RDS patients had the worst lung ultrasound score (p = 0.022) and oxygenation index (p = 0.001), while NBAP and TTN neonates had similar values. At the worst time-point, NBAP and RDS patients showed similar oxygenation index (NBAP: 4.6 [2], RDS: 5.7 [3]) and SpO2 /FiO2 (NBAP: 3.1 [1.1], RDS: 2.7 [1]) which were worse than those of TTN patients (oxygenation index: p = 0.015, SpO2 /FiO2 : p = 0.001). RDS neonates needed the longest continuous positive airway pressure and highest mean airway pressure, but NBAP neonates needed invasive ventilation (26.3%, p = 0.01) and surfactant (31.6%, p = 0.003) more often than TTN patients who never needed these. CONCLUSION: NBAP was a mild disorder in the first hours of life but subsequently worsened and became similar to RDS.

Ultrasound-assessed lung aeration correlates with respiratory system compliance in adults and neonates with acute hypoxemic restrictive respiratory failure: an observational prospective study.

BACKGROUND: Lung ultrasound allows lung aeration to be assessed through dedicated lung ultrasound scores (LUS). Despite LUS have been validated using several techniques, scanty data exist about the relationships between LUS and compliance of the respiratory system (Crs) in restrictive respiratory failure. Aim of this study was to investigate the relationship between LUS and Crs in neonates and adults affected by acute hypoxemic restrictive respiratory failure, as well as the effect of patients' age on this relationship. METHODS: Observational, cross-sectional, international, patho-physiology, bi-center study recruiting invasively ventilated, adults and neonates with acute respiratory distress syndrome (ARDS), neonatal ARDS (NARDS) or respiratory distress syndrome (RDS) due to primary surfactant deficiency. Subjects without lung disease (NLD) and ventilated for extra-pulmonary conditions were recruited as controls. LUS, Crs and resistances (Rrs) of the respiratory system were measured within 1 h from each other. RESULTS: Forty adults and fifty-six neonates were recruited. LUS was higher in ARDS, NARDS and RDS and lower in control subjects (overall p < 0.001), while Crs was lower in ARDS, NARDS and RDS and higher in control subjects (overall p < 0.001), without differences between adults and neonates. LUS and Crs were correlated in adults [r = - 0.86 (95% CI - 0.93; - 0.76), p < 0.001] and neonates [r = - 0.76 (95% CI - 0.85; - 0.62), p < 0.001]. Correlations remained significant among subgroups with different causes of respiratory failure; LUS and Rrs were not correlated. Multivariate analyses confirmed the association between LUS and Crs both in adults [B = - 2.8 (95% CI - 4.9; - 0.6), p = 0.012] and neonates [B = - 0.045 (95% CI - 0.07; - 0.02), p = 0.001]. CONCLUSIONS: Lung aeration and compliance of the respiratory system are significantly and inversely correlated irrespective of patients' age. A restrictive respiratory failure has the same ultrasound appearance and mechanical characteristics in adults and neonates.

Semi-quantitative lung ultrasound score during ground transportation of outborn neonates with respiratory failure.

Lung ultrasound score (LUS) is increasingly diffused in neonatal critical care but scanty data are available about its use during transfer of severely ill neonates. We aimed to clarify the effect of ground transportation on LUS evolution, conformity of interpretation, and relationships with oxygenation and clinical severity. This is a single-center, blinded, observational, cross-sectional study. Neonates of any gestational age with respiratory distress appearing within 24 h from birth were transferred by a mobile unit towards neonatal intensive care unit (NICU) of a tertiary referral center. Calculation of LUS prior to the transportation (T1), in the mobile unit (T2), at the end of transportation (T3), and finally upon NICU admission. LUS in the mobile unit and in the NICU was performed by different physicians blinded to each other's results. LUS did not change overtime (T1: 6.3 (3.5), T2: 6.1 (3.5), T3: 5.8 (3.4); p = 0.479; adjusted for gestational or postnatal age or transport duration: p = 0.951, p = 0.424, and 0.266, respectively) but reliably predicted surfactant need (AUC at T1: 0.833 (95%CI: 0.72-0.92); AUC at T2: 0.82 (95%CI: 0.70-0.91); AUC at T3: 0.82 (95%CI: 0.70-0.90); p always < 0.0001). There were significant agreement (ICC = 0.912 (95%CI: 0.83-0.95); p < 0.001) and correlation (r = 0.905, p < 0.001) between LUS calculated during transportation and in the NICU. LUS during transportation was also significantly correlated with oxygenation index (r = 0.321, p = 0.026; standardized B = 0.397 (95%CI: 0.03-0.76), p = 0.048) and TRIPS-II score (r = 0.302, p = 0.008; standardized B = 0.568 (95%CI: 0.04-1.1), p = 0.037). CONCLUSION: LUS during ground transportation of neonates with respiratory failure is suitable and not influenced by the transportation itself. It has a high agreement with that calculated in the NICU and correlates with patients' oxygenation and severity. WHAT IS KNOWN: • Lung ultrasound is a part of the point-of-care ultrasound, which is becoming an essential tool, to manage critically ill neonates and children in an accurate, non-invasive and quick way. WHAT IS NEW: • Lung ultrasound score (LUS) is suitable during transportation of critically ill neonates with respiratory failure and is not influenced by the transportation itself. • LUS has a high agreement with that calculated in the NICU and correlates with patients' oxygenation and severity of respiratory failure.

Enhanced INSURE (ENSURE): an updated and standardised reference for surfactant administration.

There is no firm consensus about the optimal technique for the administration of exogenous surfactant in preterm neonates, and different techniques may be equally effective. The intubation-surfactant-extubation (INSURE) procedure has not been fully described, and important details, such as duration and mode of ventilation, remain unclear, leading to significant clinical practice variations and influencing its suitability and feasibility. Since the first INSURE description, our knowledge in respiratory care has largely progressed, but the technique has not been updated according to current evidence-based practice. Thus, our aim is to formally describe a modern way to perform INSURE, based on the current knowledge and technology, to increase its feasibility and patients' safety. We offer ENSURE (Enhanced INSURE) as an updated and standardised technique for surfactant administration, clarifying crucial issues of the original method by applying current state-of-the-art concepts of respiratory care. We performed a cross-sectional observational study enrolling 57 preterm neonates describing ENSURE feasibility and safety.   Conclusion: ENSURE can be used as a reference technique in clinical practice, teaching and research. What is Known: • There is no consensus about the optimal method for surfactant administration. INSURE technique has been originally described many years ago without considering modern principles of neonatal respiratory care and the available state-of-the-art technology. What is New: • We here describe a modern way to perform INSURE, based on the current knowledge and technology. We called it ENSURE (Enhanced INSURE) and clarified crucial points of the original technique, in light of the current knowledge. We verified feasibility and safety of ENSURE in a cross-sectional observational study enrolling 57 preterm neonates.

Lung Ultrasound to Monitor Extremely Preterm Infants and Predict Bronchopulmonary Dysplasia. A Multicenter Longitudinal Cohort Study.

Rationale: Lung ultrasound is useful in critically ill patients with acute respiratory failure. Given its characteristics, it could also be useful in extremely preterm infants with evolving chronic respiratory failure, as we lack accurate imaging tools to monitor them. Objectives: To verify if lung ultrasound can monitor lung aeration and function and has good reliability to predict bronchopulmonary dysplasia in extremely preterm neonates. Methods: A multicenter, international, prospective, longitudinal, cohort, diagnostic accuracy study consecutively enrolling inborn neonates with gestational age 30+6 weeks or younger. Lung ultrasound was performed on the 1, 7, 14, and 28 days of life, and lung ultrasound scores were calculated and correlated with simultaneous blood gases and work of breathing score. Gestational age-adjusted lung ultrasound scores were created, verified in multivariate models, and subjected to receiver operator characteristics (ROC) analyses to predict bronchopulmonary dysplasia at 36 weeks postmenstrual age. Measurements and Main Results: Mean lung ultrasound scores are different between infants developing (n = 72) or not developing (n = 75) bronchopulmonary dysplasia (P < 0.001 at any time point). Lung ultrasound scores significantly correlate with oxygenation metrics and work of breathing at any time point (P always < 0.0001). Gestational age-adjusted lung ultrasound scores significantly predict bronchopulmonary dysplasia at 7 (area under ROC curve, 0.826-0.833; P < 0.0001) and 14 (area under ROC curve, 0.834-0.858; P < 0.0001) days of life. Bronchopulmonary dysplasia severity and gestational age-adjusted lung ultrasound scores are significantly correlated at 7 and 14 days (P always < 0.0001). Conclusions: Lung ultrasound scores allow monitoring of lung aeration and function in extremely preterm infants. Gestational age-adjusted scores significantly predict the occurrence of bronchopulmonary dysplasia, starting from the seventh day of life.

Synthetic cannabinoids: the hidden side of Spice drugs.

Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to mimic the psychoactive ingredient in marijuana [Δ-tetrahydrocannabinol (Δ-THC)] and synthesized by introducing modifications to the chemical structure of parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid use/abuse can be devastating as toxicological effects and adverse reactions cannot be entirely predicted and may vary with the dose, route of administration, individual vulnerability and concomitant intake with other drugs. The absence of validated testing procedures in the clinical field makes difficult the adoption of a therapeutic approach effective in coping with the synthetic cannabinoid phenomenon, posing a significant challenge for prevention, treatment and public health in general. The aim of this review is to gain insights into the epidemiological, pharmacological and toxicological properties of synthetic cannabinoids, aiming to provide a reliable background needed for the management of synthetic cannabinoid-related adverse effects. Consumers, competent authorities and medical care professionals should be aware of the risks associated with synthetic cannabinoid use.

4,4'-Dimethylaminorex ("4,4'-DMAR"; "Serotoni") misuse: A Web-based study.

BACKGROUND: 4,4'-DMAR (4,4'-dimethylaminorex; "Serotoni") is a potent stimulant drug that has recently been associated with a number of fatalities in Europe. Over the last few years, online communities have emerged as important resources for disseminating levels of technical knowledge on novel psychoactive substances. OBJECTIVE: Analysing the information provided by the fora communities on 4,4'-DMAR use, additionally critical reviewing the available evidence-based literature on this topic. METHODS: Different website drug fora were identified. A critical review of the existing evidence-based literature was undertaken. Individuation and analysis of qualitative data from the identified website fora were performed. RESULTS: The combined search results identified six website fora from which a range of qualitative data on recurring themes was collected. These themes included routes of administration and doses; desired effects; adverse effects; comparison with other drugs; association with other drugs; medications self-administered to reverse 4,4'-DMAR action; overall impression; and provision of harm-reduction advice. CONCLUSIONS: Although being characterized by a number of methodological limitations, the social networks' Web monitoring approach (netnography) may be helpful to better understand some of the clinical and psychopharmacological issues pertaining to a range of novel psychoactive substances, including 4,4'-DMAR, for which only extremely little, if any, scientific knowledge is available.

Methoxetamine-related deaths in the UK: an overview.

OBJECTIVE: The goal of this study is to provide an update on the data given on methoxetamine (MXE)-related fatalities that occurred in 2011-2013, presented at the Second International Conference on Novel Psychoactive Substances. METHODS: Fatalities involving MXE were extracted from the database of the National Programme on Substance Abuse Deaths, which receives information on drug-related deaths from Coroners in the UK and Islands (Isle of Man, Jersey, Guernsey) and other data suppliers. RESULTS: Eight cases, received by 3 September 2013, in which MXE was found at post-mortem and/or directly implicated in the death and/or mentioned in the Coroner's verdict are described. The median age at death was 27 years, with the majority of White ethnicity (6/8) and male (7/8). MXE was used together with other substances in 7/8 cases. MXE was found at post-mortem in all cases, directly implicated in the deaths of four and likely to have had an influence in two. CONCLUSIONS: More research needs to be conducted into its health effects and toxicity potential. Health care professionals should be made aware of the potential health harms of MXE, in order to develop early intervention measures and minimise the number of MXE-related poisonings and fatalities.

Deaths of individuals aged 16-24 years in the UK after using mephedrone.

OBJECTIVE: Mephedrone is a stimulant drug chemically related to amphetamine, with effects similar to those of amphetamine and cocaine. This study aims to analyse fatalities following ingestion of mephedrone in the UK amongst 16- to 24-year-olds in 2009-2013, providing an update on data presented at the 2nd International Conference on Novel Psychoactive Substances. METHODS: A literature search was undertaken to identify published information on pharmacology, toxicity and fatalities associated with mephedrone. Fatalities involving mephedrone were extracted from the National Programme on Substance Abuse Deaths database, which receives information on drug-related deaths from coroners in the UK and Islands and other data suppliers. Selection criteria are as follows: deceased aged 16-24 years at time of death and mephedrone directly implicated in the cause of death and/or mentioned in the coroner's verdict. RESULTS: Thirty cases met the study criteria, and when known, all were of White ethnicity, most (85%) had a history of drug use and 73% were male. Two-thirds (63%) were accidental poisonings. Mephedrone was used with other substances in most cases (87%); other substances were implicated in 60% of deaths. CONCLUSIONS: Mephedrone use can have potentially fatal consequences, especially in combination with other substances. Deaths from its use in the 16-24 years' age group continue to occur in the UK, despite it being a controlled drug. Health professionals and potential consumers should be alert to this risk.

The dopamine ß-hydroxylase inhibitor, nepicastat, reduces different alcohol-related behaviors in rats.

BACKGROUND: Recent experimental data indicate that treatment with the selective dopamine ß-hydroxylase inhibitor, nepicastat, suppressed different reward-related behaviors, including self-administration of chocolate and reinstatement of cocaine and chocolate seeking, in rats. This study was designed to extend to different alcohol-related behaviors the investigation on the "anti-addictive" properties of nepicastat. METHODS: Sardinian alcohol-preferring (sP) rats, selectively bred for excessive alcohol consumption, were exposed to different procedures of alcohol drinking and self-administration. RESULTS: Repeated treatment with nepicastat (0, 25, 50, and 100 mg/kg, intraperitoneally [i.p.], once daily for 10 consecutive days) produced a stable and dose-related reduction in daily alcohol intake in sP rats exposed to the homecage 2-bottle "alcohol (10% v/v) versus water" choice regimen with unlimited access. Acute treatment with nepicastat (0, 25, 50, and 100 mg/kg, i.p.) completely suppressed the "alcohol deprivation effect" (i.e., the temporary increase in alcohol intake occurring after a period of abstinence; model of alcohol relapse episodes) in sP rats exposed to the 2-bottle choice regimen. Acute treatment with nepicastat (0, 25, 50, and 100 mg/kg, i.p.) dose dependently and selectively reduced oral alcohol self-administration in sP rats trained to lever respond for alcohol (15% v/v) on a fixed ratio 4 schedule of reinforcement. Finally, combination of nepicastat (0, 50, and 100 mg/kg, i.p.) and alcohol (2 g/kg, intragastrically) did not alter spontaneous locomotor activity in sP rats. CONCLUSIONS: Together, these data extend to alcohol the capacity of nepicastat to suppress different behaviors motivated by natural stimuli and drugs of abuse.

Protective effect of Panax ginseng in cisplatin-induced cachexia in rats.

AIM: This study investigated the protective effect of a standardized extract of Panax ginseng on multiple cisplatin-induced 'sickness behaviors' (model of cancer-induced cachexia) in rats. MATERIALS & METHODS: Cisplatin was administered twice weekly (1-2 mg/kg, intraperitoneal) for 5 consecutive weeks. Panax ginseng extract (0, 25 and 50 mg/kg, intragastric) was administered daily over the 5-week period of cisplatin exposure. Malaise, bodyweight and temperature, pain sensitivity, and endurance running were recorded at baseline and at 5 weekly intervals. RESULTS: Treatment with cisplatin produced severe signs of malaise, marked loss of bodyweight, hypothermia, hyperalgesia and reduction in running time. Treatment with Panax ginseng extract completely prevented all cisplatin-induced alterations. CONCLUSION: These data indicate that treatment with Panax ginseng extract exerted a protective effect in a rat model of cachexia and suggest that Panax ginseng extract may be a therapeutic promising tool for supportive care in oncology.

Quantitative Lung Ultrasonography to Guide Surfactant Therapy in Neonates Born Late Preterm and Later.

Importance: Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population. Objective: To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates. Design, Setting, and Participants: This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled. Exposure: Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making. Main Outcomes and Measures: The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed. Results: A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted ß, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted ß, 0.2; 95% CI, 0.1-0.3; P < .001). Conclusions and Relevance: In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.

Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on food intake and glycemia in rats.

Extracts from Phaseolus vulgaris and Cynara scolymus may reduce food intake and/or postprandial glycemia. This study investigated the effect of standardized extracts of P. vulgaris and C. scolymus and their combination on food intake and glycemia in rats. P. vulgaris and C. scolymus extracts, and their 1:2 combination, were administered acutely to rats (a) given access to regular food and water, (b) given access to regular food, water, and a chocolate-flavored beverage, or (c) infused with a starch bolus. P. vulgaris extract and the combination produced comparable reductions in intake of regular food and chocolate-flavored beverage; conversely, C. scolymus extract was ineffective on both parameters. P. vulgaris and C. scolymus extracts additively contributed to the reducing effect of the combination on glycemic rise. These results suggest that a mixture of P. vulgaris and C. scolymus extracts is preferable over each single extract, as it combines the anorectic effect of the P. vulgaris extract with the hypoglycemic effect of both extracts. These data support the recent clinical use of the combination of P. vulgaris and C. scolymus extracts in the control of appetite, food intake, and postprandial glycemia and represent a successful example of translational research in the nutraceutical field.

Effect of preterm chorioamnionitis on lung ultrasound score used to guide surfactant replacement.

OBJECTIVE: Lung ultrasound score (LUS) accurately guides surfactant replacement in preterm neonates with respiratory distress syndrome due to surfactant deficiency. However, surfactant deficiency is not the unique pathobiological feature, as there may be relevant lung inflammation, such as in certain cases of clinical chorioamnionitis (CC). We aim to investigate if CC influences LUS and ultrasound-guided surfactant treatment. DESIGN: Retrospective (2017-2022), large, cohort study targeted to recruit a homogeneous population treated with unchanged respiratory care policy and lung ultrasound protocol. Patients with (CC+: 207) and without (CC-: 205) chorioamnionitis were analyzed with propensity score matching and subsequent additional multivariate adjustments. RESULTS: LUS was identical at unmatched and matched comparisons. Consistently, at least one surfactant dose was given in 98 (47.3%) and 83 (40.5%) neonates in the CC+ and CC- matched cohorts, respectively (p = .210). Multiple doses were needed in 28 (13.5%) and 21 (10.2%) neonates in the CC+ and CC- cohorts, respectively (p = .373). Postnatal age at surfactant dosing was also similar. LUS was higher in patients who were diagnosed with neonatal acute respiratory distress syndrome (NARDS) (CC+ cohort: 10.3 (2.9), CC- cohort: 11.4 (2.6)), than in those without NARDS (CC+ cohort: 6.1 (3.7), CC- cohort: 6.2 (3.9); p < .001, for both). Surfactant use was more frequent in neonates with, than in those without NARDS (p < .001). Multivariate adjustments confirmed NARDS as the variable with greater effect size on LUS. CONCLUSIONS: CC does not influence LUS in preterm neonates, unless inflammation is enough severe to trigger NARDS. The occurrence of NARDS is key factor influencing the LUS.