Optimizing Oxygen Delivery by Low-Flow Nasal Cannula to Small Infants: A Bench Study.

BACKGROUND: In infants treated with a low-flow nasal cannula (LFNC), the oxygen concentration delivered to the lungs (i.e., the effective FiO2) is difficult to estimate. The existing mathematical formulas rely on important assumptions regarding the values of respiratory parameters and, thus, may be inaccurate. We aimed to assess oxygen delivery by LFNC to small infants using realistic simulations on a mechanical breathing model. METHODS: A mechanical breathing simulator (infant upper-airway replica, single-space breathing compartment, electric motor, microcontroller) was developed. Breathing simulations (n = 1200) were performed at various tidal volume (VT), inspiratory time (Ti), and respiratory rate (RR) combinations and different cannula flows. RESULTS: Minute ventilation (MV) was the most significant predictor of effective FiO2. FiO2 was higher at lower VT and higher Ti values. Benaron and Benitz's formula underestimated the effective FiO2 at lower MV values, while Finer's formula significantly overestimated it. A set of predictive FiO2 charts was developed based on cannula flow, infant body weight, and RR. CONCLUSIONS: The effective FiO2 delivered by LFNC to small infants critically depends on VT, Ti, and RR. However, since VT and Ti values are not available in clinical practice, the existing mathematical formulas may be inaccurate. Our novel predictive FiO2 charts could assist in optimizing oxygen delivery by LFNC using easy-to-obtain parameters, such as infant body weight and RR.

New Clinical Markers of Oxidized Lipid-Associated Protein Damage in Children and Adolescents with Obesity.

Obesity in children and adolescents has been associated with oxidative stress (OS). The lipid hydroperoxides (LOOH) and the malondialdehyde (MDA) and thiobarbituric reactive substances (TBARS) that oxidatively modify proteins (Pr) (i.e., PrMDA and PrTBARS, respectively) represent markers of OS-associated lipid peroxidation. We aimed to assess OS in children and adolescents with obesity using-for the first time-markers involved in the early and late lipid oxidation process. LOOH, PrMDA, and PrTBARS were investigated in 41 children and adolescents with obesity and 31 controls. Obesity was defined as BMI > 95% for age and sex. The PrMDA/PrTBARS pair, which reflects a late peroxidation stage, was found to be significantly high (39%/180%) in children and adolescents with obesity compared to controls (p < 0.001). Similarly, the early LOOH peroxidation stage marker was increased by 30%. The studied OS parameters were not influenced by sex or age. Our study introduces LOOH, PrTBARS, and PrMDA as markers for evaluating OS in children and adolescents with obesity. LOOH, PrTBARS, and PrMDA may also hold promise as prognostic markers for potential obesity-associated long-term complications.

Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

PURPOSE: We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. METHODS: Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. RESULTS: The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). CONCLUSIONS: Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Cardiopulmonary Exercise Performance of Children Born Non-Extremely Preterm.

Data on exercise tolerance of children born non-extremely preterm are sparse. We aimed to explore the cardiopulmonary exercise testing (CPET) characteristics in this population. We studied 63 children (age 7-12 years) born at 290/7-366/7 weeks of gestation (34 were late preterm, 29 were preterm) and 63 age-matched, term-born controls. All performed spirometry and CPET (cycle ergometry). There were no differences in activity levels and spirometric parameters between the group of preterm-born children and controls. A peak oxygen uptake (VO2peak) of <80% was noted in 25.4% of the term-born and 49.2% of preterm-born children (p = 0.001). Term-born participants presented similar VO2peak to late-preterm children but higher than those born at <340/7 weeks of gestation (p = 0.002). Ventilatory limitation was noted in 4.8% of term and 7.9% of preterm participants, while only one preterm child presented cardiovascular limitation. Children born before 34 weeks of gestation had higher respiratory rates and smaller tidal volumes at maximum exercise, as well as lower oxygen uptake for the level of generated work. We conclude that school-age children born at 29-34 weeks of gestation may present decreased exercise performance attributed to an altered ventilatory response to exercise and impaired O2 utilization by their skeletal muscles rather than other cardiopulmonary limiting factors.

Monocyte Chemoattractant Protein-1 (MCP-1), Activin-A and Clusterin in Children and Adolescents with Obesity or Type-1 Diabetes Mellitus.

Inflammation plays a crucial role in diabetes and obesity through macrophage activation. Macrophage chemoattractant protein-1 (MCP-1), activin-A, and clusterin are chemokines with known roles in diabetes and obesity. The aim of this study is to investigate their possible diagnostic and/or early prognostic values in children and adolescents with obesity and type-1 diabetes mellitus (T1DM). METHODS: We obtained serum samples from children and adolescents with a history of T1DM or obesity, in order to measure and compare MCP-1, activin-A, and clusterin concentrations. RESULTS: Forty-three subjects were included in each of the three groups (controls, T1DM, and obesity). MCP-1 values were positively correlated to BMI z-score. Activin-A was increased in children with obesity compared to the control group. A trend for higher values was detected in children with T1DM. MCP-1 and activin-A levels were positively correlated. Clusterin levels showed a trend towards lower values in children with T1DM or obesity compared to the control group and were negatively correlated to renal function. CONCLUSIONS: The inflammation markers MCP-1, activin-A, and clusterin are not altered in children with T1DM. Conversely, obesity in children is positively correlated to serum MCP-1 values and characterized by higher activin-A levels, which may reflect an already established systematic inflammation with obesity since childhood.

Nasopharyngeal cyst in an adolescent boy: differential diagnosis - embryological and anatomical considerations.

In the current article, we present a case of an adolescent boy with a nasopharyngeal cyst that induced nasal and Eustachian tube obstruction. Nasopharyngeal cysts can be found incidentally during imaging examinations such as MRI; however, a symptomatic nasopharyngeal cyst is a rare finding in the paediatric population. The cyst was treated successfully by marsupialisation, and the histological diagnosis revealed an adenoidal retention cyst. The differential diagnosis of a nasopharyngeal cyst is always challenging since developmental cysts such as Rathke's pouch cysts, Torwaldt's and branchial cleft cysts may be encountered at the nasopharynx. The current article also intends to present the diagnostic and therapeutic approach to a nasopharyngeal cyst, emphasising anatomical and embryological considerations that address its differential diagnosis.

Diaphragmatic muscle function in term and preterm infants.

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia-BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)-a measure of diaphragmatic strength, and the pressure-time index of the diaphragm (PTIdi)-a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi.  Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function. What is Known: • The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively. • The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure-time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants. What is New: • Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. • In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

Translation and Validation Study of the Hypoglycemia Fear Survey in a Greek Population of Children and Adolescents with Type 1 Diabetes Mellitus and their Parents.

The present study attempted to translate and culturally adapt an established research instrument, the Hypoglycemia Fear Survey (HFS) questionnaire, to the Greek population and evaluate its validity and internal consistency so that it can be used for the assessment of hypoglycemia fear in Greek children and adolescents with T1DM and their parents. One hundred Greek children and adolescents with T1DM, 54 males, 6-18 years old, and one of their parents participated in this validation study. The participants completed the translated Greek HFS, which includes one version for children (CHFS) and one for parents (PHFS). Exploratory Factor Analysis (EFA) was used to assess construct validity. Internal consistency was assessed using Cronbach's alpha, and convergent validity was established by estimating the correlation coefficients between the scores of the HFS scales/subscales and the different constructs of the Pediatric Quality of Life Inventory. The CHFS and PHFS exhibited adequate internal consistency for the total score and the Worry subscale, but lower consistency for the Behavior subscale. High test-retest reliability was also shown. We conclude that the Greek version of the HFS is a valid and reliable instrument to assess the fear of hypoglycemia in Greek children and adolescents with T1DM and their parents.

A Clinical Approach of Allergic Rhinitis in Children.

Allergic rhinitis is an important disease with a global footprint and a growing prevalence, affecting children and adults. Although it is commonly under-diagnosed and under-treated, it causes important social and economic effects (diminished quality of life, poor academic performance, escalated medical visits, heightened medication usage, and effects in other chronic conditions, e.g., asthma). It is characterized by distinctive, easily identifiable symptoms (sneezing, nasal discharge, nasal congestion, nasal-eye-palatal itching) and indirect accompanying indicators (fatigue and decreased school performance). The classification of allergic rhinitis hinges upon its nature and chronic distribution (seasonal or perennial) and its intensity, which spans from mild to moderate and severe. The diagnostic process primarily relies upon recognizing key clinical indicators, evaluating historical records, and considering risk factors. It is supported by abnormal laboratory findings, like in vitro allergen-specific IgE tests (enzyme immunoassay-EIA, chemiluminense immunoassay-CLIA) or in vivo skin prick tests for specific allergens. In the differential diagnosis, other chronic diseases manifesting with chronic rhinitis should be excluded (e.g., rhinosinusitis, chronic non-allergic rhinitis, rhinitis triggered by medications). The treatment of allergic rhinitis in children is mainly chronic and is focused on allergen exposure prevention, drug therapy, and immunotherapy in severe cases. Locally administered intranasal corticosteroids are the cornerstone of therapy. They are safe, effective, and have a favorable safety profile even during long-term use. Choosing a suitable intranasal corticosteroid drug with low systemic bioavailability makes long-term treatment even safer. Combinations of intranasal corticosteroids and H1 antihistamines are available in several countries and are widely used in more severe cases and the presence of year-round symptoms. Adding newer-generation oral H1-antihistamines broadens the available therapeutic inventory without significant effects compared to using previous-generation, once widely available, H1-antihistamines. Treatment of allergic rhinitis is complex and multi-dimensional, requiring an effective approach by a specialized group of specialized pediatricians, and is severely affected by the concurrent presence or development of other diseases in the spectrum of allergic diseases (conjunctivitis, asthma).

Infantile hemangiomas screening modalities for primary care physicians.

Infantile hemangiomas are the most common benign vascular tumors in children. They present a characteristic natural history of spontaneous involution after a phase of initial proliferation. A small but significant minority demonstrates incomplete regression or complications and requires prompt intervention. Prediction of the evolution of infantile hemangiomas is challenging because of their morphological and behavioral heterogeneity. The decision between referral for treatment and observation is sometimes difficult, especially among non-expert physicians, with the risk of missing the period for optimizing outcomes in case of delayed intervention. The aim of this review is to update our knowledge, especially of the primary care providers, regarding the ongoing difficulties of the early clinical evaluation of infantile hemangiomas, and to outline the importance of current practical scoring tools for the identification of the lesions which require expert consultation and referral.

Low-frequency oscillometry indices to assess ventilation inhomogeneity in CF patients.

BACKGROUND: The utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower-frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity. METHODS: Forty-five children, adolescents, and adults with CF (age 6.9-27 years) underwent spirometry, FOT, and nitrogen multiple-breath washout (N2-MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity. RESULTS: The sGrs correlated well with the lung clearance index (LCI) (Spearman's r: -.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and -.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices. CONCLUSIONS: In CF patients, the FOT indices at 5 Hz and the novel, volume-adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2-MBW. Future research should explore the role of lower-frequency FOT in assessing the severity and monitoring the progression of CF lung disease.

Diabetic Ketoacidosis in Children and Adolescents; Diagnostic and Therapeutic Pitfalls.

Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, Type 2 Diabetes Mellitus (T2DM) in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia, and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline and Scopus databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, between DKA and hyperosmolar hyperglycaemic state (HHS), and between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen, and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration, restoration of shifting electrolyte disorders and addressing underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention, and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

Post-Traumatic Stress as a Psychological Effect of Mild Head Injuries in Children.

BACKGROUND: Head trauma is one of the most common pediatric emergencies. While the psychological effects of severe head injuries are well studied, the psychological consequences of mild head injuries often go overlooked. Head injuries with a Glasgow Coma Scale score of 13-15, with symptoms such as headache, vomiting, brief loss of consciousness, transient amnesia, and absence of focal neurological signs, are defined as mild. The aim of this study is to evaluate the stress of children with mild head injuries and their parents' relevant perception during the early post-traumatic period. METHODS: This is a prospective cross-sectional study on a cohort of children with mild head injuries and their parents. Two questionnaires were implemented, the Child Trauma Screening Questionnaire (CTSQ) which was compiled by the children, and the Children's Revised Impact of Event Scale (CRIES-13), compiled by their parents. Both questionnaires are widely used and reliable. The first presents an excellent predictive ability in children with a risk of post-traumatic stress disorder, while the second is a weighted self-completed detecting instrument for the measurement of post-traumatic stress in children and adolescents, with a detailed evaluation of their reactions to the traumatic incident. The participants responded one week and one month after the traumatic event. RESULTS: A total of 175 children aged 6-14 years and 174 parents participated in the study. Stress was diagnosed in 33.7% of children after one week, and in 9.9% after one month. Parental responses suggesting stress presence in their children were 19.0% and 3.9%, respectively. These outcomes showed that mild head injuries are not so innocent. They are often underestimated by their parents and may generate a psychological burden to the children during the early post-traumatic period. CONCLUSIONS: Mild head injuries may affect the emotional welfare of children. Healthcare providers should understand the importance of the psychological effect of this overlooked type of injury. They should be trained in the psychological effect of trauma and be aware of this probability, promptly notify the parents accordingly, and provide psychological assistance beyond medical treatment. Follow-up and support are needed to avoid the possibility of future post-traumatic stress disorder. More extensive research is needed as the outcomes of this study regarded a limited population in numbers, age, and survey period. Furthermore, many children with mild head injuries do not ever visit the emergency department and stay at home unrecorded. Community-based research on the topic should therefore be considered.

Association of the Bacteria of the Vermiform Appendix and the Peritoneal Cavity with Complicated Acute Appendicitis in Children.

BACKGROUND: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. METHODS: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to identify if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. RESULTS: Escherichia coli, Pseudomonas aeruginosa, and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria and polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented a four times higher risk of complicated appendicitis. CONCLUSIONS: Polymicrobial presentation and Gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

Body-Size Misperception among Overweight Children and Adolescents in Greece: A Cross-Sectional Study.

Childhood obesity can affect both physical and mental health. Body-size misperception may lead to a lack of motivation to make healthy changes or to engage in unhealthy weight loss behaviors, increasing the possibility for obese children to become obese adults. To estimate the frequency of body-size misperception among children and adolescents, we conducted a cross-sectional study within another study on eating disorders in youth in Greece (National Institute of Educational Policy, act no. 04/2018). Between January and December 2019, two trained assistants visited 83 primary and secondary schools of the Region of Western Greece and interviewed 3504 children aged 10-16 years (CL 99%) and performed anthropometric measurements. Among the 3504 surveyed children, 1097 were overweight, including 424 obese, and 51 were underweight. The "perceived" BMI was not computed in 875 children (25%), who did not state their weight or height and were classified as non-responders. Weight bias was inversely related to BMI, the obese and overweight non-obese children underestimated their weight, while the underweight children overestimated it. Conversely, height bias was positively related to BMI bias. BMI bias was not related to sex, age, parental education, or place of residence. In conclusion, our study lends robust support to the existing evidence on unrealistic body images among overweight children and adolescents. Prompt recognition of such misperceptions may help in increasing motivation towards healthier eating habits, systematic physical activity, and weight-control interventions.

Novel Indices to Improve the Diagnostic Ability of Nocturnal Oximetry in Children with OSAS.

Nocturnal pulse oximetry (NOx) is an alternative diagnostic test for obstructive sleep apnea syndrome (OSAS) in childhood yet with variable diagnostic performance. Our aim was to apply advanced signal analysis to develop novel and more accurate NOx indices. We studied 45 children aged 3-10 years who underwent adenotonsillectomy for adenotonsillar hypertrophy and OSAS symptoms. Participants performed NOx before and three months after surgery, and the changes in McGill oximetry score (MOS), oxygen desaturation ≥3% index (ODI3), and the novel parameters-cumulative saturation area (CSA) and oxygen saturation sample entropy (SSE)-were assessed. There was a significant improvement (p < 0.001) in all NOx indices. When pre- and post-adenotonsillectomy NOx recordings were compared, the MOS had an area under the curve (AUC) of 0.811 with 63.2% sensitivity and 100% specificity at a cutoff >1. The AUC of ODI3 was 0.994, with 97.8% sensitivity and 91.1% specificity at a cutoff of >3.6 events per hour. The CSA and SSE had an AUC of 1.00, with 100% sensitivity and specificity at a cutoff of >293 and >0.99, respectively. We conclude that the herein-introduced indices-CSA and SSE-hold promise in improving the diagnostic ability of NOx in children suspected of OSAS.

Early Diagnosis of Late-Onset Neonatal Sepsis Using a Sepsis Prediction Score.

Sepsis represents a common cause of morbidity in the Neonatal Intensive Care Unit (NICU). Our objective was to assess the value of clinical and laboratory parameters in predicting septicemia (positive blood culture) in NICU infants. In the first part of the present study (derivation cohort) we retrospectively reviewed the clinical files of 120 neonates with symptoms of suspected sepsis and identified clinical and laboratory parameters associated with proven sepsis on the day the blood culture was taken, as well as 24 h and 48 h earlier. These parameters were combined into a sepsis prediction score (SPS). Subsequently (validation study), we prospectively validated the performance of the SPS in a cohort of 145 neonates. The identified parameters were: temperature instability, platelet count < 150,000/mm3, feeding volume decrease > 20%, changes in blood glucose > 50%, CRP > 1 mg/dL, circulatory and respiratory deterioration. In the retrospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 82.54% sensitivity, 85.96% specificity, 5.88 PLR (Positive Likelihood Ratio), 0.20 NLR (Negative Likelihood Ratio), 86.67% PPV (Positive Predictive Value), 81.67% NPV (Negative Predictive Value) and 84.17% accuracy. In the prospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 76.60% sensitivity, 72.55% specificity, 2.79 PLR, 0.32 NLR, 83.72% PPV, 62.71% NPV and 75.17% accuracy. We concluded that this combination of clinical and laboratory parameters may assist in the prediction of septicemia in NICUs.

Antibiotic Resistance in Patients with Cystic Fibrosis: Past, Present, and Future.

Patients with cystic fibrosis (CF) are repeatedly exposed to antibiotics, especially during the pulmonary exacerbations of the disease. However, the available therapeutic strategies are frequently inadequate to eradicate the involved pathogens and most importantly, facilitate the development of antimicrobial resistance (AMR). The evaluation of AMR is demanding; conventional culture-based susceptibility-testing techniques cannot account for the lung microenvironment and/or the adaptive mechanisms developed by the pathogens, such as biofilm formation. Moreover, features linked to modified pharmaco-kinetics and pulmonary parenchyma penetration make the dosing of antibiotics even more challenging. In this review, we present the existing knowledge regarding AMR in CF, we shortly review the existing therapeutic strategies, and we discuss the future directions of antimicrobial stewardship. Due to the increasing difficulty in eradicating strains that develop AMR, the appropriate management should rely on targeting the underlying resistance mechanisms; thus, the interest in novel, molecular-based diagnostic tools, such as metagenomic sequencing and next-generation transcriptomics, has increased exponentially. Moreover, since the development of new antibiotics has a slow pace, the design of effective treatment strategies to eradicate persistent infections represents an urgency that requires consorted work. In this regard, both the management and monitoring of antibiotics usage are obligatory and more relevant than ever.

Validation of a non-invasive pressure-time index of the inspiratory muscles in spontaneously breathing newborn infants.

To validate the pressure-time index of the inspiratory muscles as a non-invasive index of inspiratory muscle function in spontaneously breathing infants by comparing it against the gold-standard pressure-time index of the diaphragm. Prospective observational cohort study of consecutive infants breathing unsupported in room air in a tertiary neonatal intensive care unit, studied prior to discharge from neonatal care. The invasive pressure-time index of the diaphragm was calculated using a transdiaphragmatic dual-pressure catheter that measured transdiaphragmatic pressure by subtraction of the oesophageal from the gastric pressure. The non-invasive pressure-time index of the inspiratory muscles was calculated using pressure measurements at the level of the mouth via a differential pressure transducer connected to a face mask. Both indices were calculated as the product of the ratio of the mean inspiratory pressure divided by the maximum inspiratory pressure and the ratio of the inspiratory time divided by the total time of a respiratory cycle. One hundred and thirty infants (79 male) were included with a mean (SD) gestational age of 35.2 (3.2) weeks, studied at a median (IQR) postnatal age of 9 (6-20) days. The mean (SD) pressure-time index of the diaphragm was 0.063 (0.019) and the mean (SD) pressure-time index of the inspiratory muscles was 0.065 (0.023). The correlation coefficient for the two indices was 0.509 (p < 0.001). The mean (SD) absolute difference between the pressure-time index of the inspiratory muscles and pressure-time index of the diaphragm was 0.002 (0.021). In convalescent infants, the non-invasive pressure-time index of the inspiratory muscles had a moderate degree of correlation with the invasively derived pressure time index of the diaphragm measured with a transdiaphragmatic catheter.

Preterm newborns exposed to early-onset preeclampsia have altered postnatal Tumor Necrosis Factor-related apoptosis-inducing ligand trends versus controls.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein with anti-atherogenic and vasoprotective effects that has never been studied in newborns exposed to preeclampsia. Our aim was to examine TRAIL serum concentrations in such neonates after birth and during the transitional period. METHODS: Serum TRAIL levels were measured on the first and fifth day of life (DOL1 and DOL5, respectively) in 38 newborns exposed to early-onset preeclampsia and 38 controls born of normotensive mothers. RESULTS: TRAIL values on DOL1 and DOL5 did not differ between cases and controls. However, from DOL1 to DOL5 TRAIL levels increased in controls (from 20.54 ± 7.35 to 23.93 ± 11.02 pg/ml, p = 0.044) but decreased in those exposed to preeclampsia (from 25.58 ± 15.74 to 20.53 ± 10.72 pg/ml, p = 0.035). Overall, the relative change of TRAIL values from DOL1 to DOL5 was positively related to birth weight (beta coefficient 0.234, p = 0.042) and inversely related to preeclampsia (beta coefficient -0.241, p = 0.036). CONCLUSION: Newborns exposed to early-onset preeclampsia present a decrease in serum TRAIL levels during the transitional period. This pattern is exactly the opposite from what is observed in neonates born to normotensive mothers, and most likely points towards a defective mechanism of extrauterine adaptation related to preeclampsia exposure in utero. IMPACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels during the transitional period do not differ between infants exposed to early-onset preeclampsia and controls The pattern of change of TRAIL levels after birth is different; TRAIL decreases in newborns exposed to preeclampsia but increases in controls The decrease of TRAIL levels during the transitional period points towards a defective mechanism of extrauterine adaptation and an altered cardiometabolic profile in newborns exposed to early-onset preeclampsia.