Sirolimus-coated balloon in all-comer population of coronary artery disease patients: the EASTBOURNE DIABETES prospective registry.

BACKGROUND: The outcomes of percutaneous coronary intervention (PCI) in diabetic patients are still suboptimal, and it is unclear if diabetic patients might derive a benefit from the use of drug-coated balloons. AIMS: To evaluate the impact of diabetes mellitus on the outcomes of patients undergoing PCI with sirolimus-coated balloon (SCB) MagicTouch (Concept Medical, India). METHODS: We conducted a subgroup analysis of the prospective, multicenter, investigator-initiated EASTBOURNE registry, evaluating the performance of MagicTouch SCB in patients with and without diabetes. The study primary endpoint was target lesion revascularization (TLR) at 12-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, myocardial infarction (MI), and BARC 2-5 bleedings. RESULTS: Among 2,083 enrolled patients, a total of 864 suffered from diabetes (41.5%). Patients with diabetes had a numerically higher occurrence of TLR (6.5% vs. 4.7% HR 1.38, 95%CI 0.91-2.08), all-cause death (3.8% vs. 2.6%, HR 1.81, 95%CI 0.95-3.46), and MACE (12.2% vs. 8.9%; HR 1.26 95%CI 0.92-1.74). The incidence of spontaneous MI was significantly higher among diabetic patients (3.4% vs. 1.5%, HR 2.15 95%CI 1.09-4.25); bleeding events did not significantly differ. The overall incidence of TLR was higher among in-stent restenosis (ISR) as compared to de-novo coronary lesions, irrespectively from diabetes status. CONCLUSIONS: In the EASTBOURNE DIABETES registry, diabetic patients treated with the MagicTouch SCB did not have a significant increase in TLR when compared to non-diabetic patients; moreover, diabetic status did not affect the study device performance in terms of TLR, in both de-novo lesions and ISR.

Long-lasting effects of COVID-19 pandemic on hospitalizations and severity of bronchiolitis.

Bronchiolitis is a common cause of hospitalization in infants. The long-lasting impact of hygiene and social behavior changes during the pandemic on this disease is debated. We investigated the prevalence of hospitalized cases, clinical severity, and underlying risk factors before and during pandemic. The study was conducted in 27 hospitals in Italy and included infants hospitalized for bronchiolitis during the following four periods: July 2018-March 2019, July 2020-March 2021, July 2021-March 2022, and July 2022-March 2023. Data on demographics, neonatal gestational age, breastfeeding history, underlying chronic diseases, presence of older siblings, etiologic agents, clinical course and outcome were collected. A total of 5330 patients were included in the study. Compared to 2018-19 (n = 1618), the number of hospitalizations decreased in 2020-21 (n = 121). A gradual increase was observed in 2021-22 (n = 1577) and 2022-23 (n = 2014). A higher disease severity (need and length of O2-supplementation, need for non-invasive ventilation, hospital stay) occurred in the 2021-22 and, especially, the 2022-23 periods compared to 2018-19. This tendency persisted after adjusting for risk factors associated with bronchiolitis severity.   Conclusions: Compared to adults, COVID-19 in infants is often asymptomatic or mildly symptomatic and rarely results in hospitalization. This study indicates that the pandemic has indirectly induced an increased burden of bronchiolitis among hospitalized infants. This shift, which is not explained by the recognized risk factors, suggests the existence of higher infant vulnerability during the last two seasons. What is known: • The pandemic led to a change in epidemiology of respiratory diseases • Large data on severity of bronchiolitis and underlying risk factors before and during COVID-19 pandemic are scarce What is new: • Compared to pre-pandemic period, hospitalizations for bronchiolitis decreased in 2020-21 and gradually increased in 2021-22 and 2022-23 • Compared to pre-pandemic period, higher disease burden occurred in 2021-22 and, especially, in 2022-23. This tendency persisted after adjusting for risk factors associated with bronchiolitis severity • The interplay among viruses, preventive measures, and the infant health deserves to be further investigated.

Sirolimus-coated balloon in acute and chronic coronary syndromes: subanalysis of the EASTBOURNE registry.

INTRODUCTION AND OBJECTIVES: The PEACE study (Performance of a sirolimus-eluting balloon strategy in acute and chronic coronary syndromes) investigated for the first time whether a sirolimus-coated balloon (SCB) (Magic Touch, Concept Medical, India) is associated with different outcomes depending on whether it is used in acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). METHODS: This was a post-hoc analysis from the all-comers EASTBOURNE Registry (NCT03085823). Out of 2083 patients enrolled, an SCB was used to treat 968 (46.5%) ACS and 1115 (53.5%) CCS patients. The primary endpoint was target lesion revascularization at 12 months, while secondary endpoints were angiographic success and major adverse cardiovascular events. RESULTS: Baseline demographics, mean reference vessel diameter and mean lesion length were comparable between ACS and CCS. Predilatation was more commonly performed in ACS (P=.007). SCB was inflated at a standard pressure in both groups with a slight trend toward longer inflation time in ACS. Angiographic success was high in both groups (ACS 97.4% vs CCS 97.7%, P=.820) with limited bailout stenting. Similarly, at 12 months the cumulative incidence of target lesion revascularization (ACS 6.6% vs CCS 5.2%, P=.258) was comparable between ACS and CCS. Conversely, a higher rate of major adverse cardiovascular events in acute presenters was mainly driven by myocardial infarction recurrencies (ACS 10.4% vs CCS 8.3%, P=.009). In-stent restenosis showed a higher proportion of target lesion revascularization and major adverse cardiovascular events than de novo lesions, independently of the type of presentation at the index procedure. CONCLUSIONS: This SCB shows good performance in terms of acute and 1-year outcomes independently of the clinical presentation.

Effectiveness of rehabilitation intervention in persons with Friedreich ataxia.

Introduction: The relevance of rehabilitation in progressive neurological disorders, such as Friedreich's Ataxia (FRDA), has yet to be convincingly proven. FRDA is characterized by ataxia, loss of gait, scoliosis, cardiomyopathy, dysarthria and dysphagia, with reduced life expectancy. The disease onset is usually in adolescence, leading to progressive disability. Omaveloxolone has been recently approved as the first pharmacological treatment for FRDA in adults and adolescents aged 16 years and older. Regarding non-pharmacological therapies, neurorehabilitation is a valuable aid in addressing the symptoms and in maintaining the residual functioning. We performed a prospective observational cohort study to evaluate the efficacy of inpatient rehabilitation (IR) for people with FRDA. Methods: A total of 42 individuals (29 adults and 13 children) with FRDA were recruited. There were 27 ambulant and 15 non-ambulant participants. The patients underwent IR of 3 and 4 weeks in children and adults, respectively. The IR treatment was designed to be applied within a multidisciplinary setting, so FRDA patients underwent, in addition to physiotherapy, also occupational therapy, practical manual activities and psychological support aiming to enhance transferable skills useful in the activities of daily living. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA). Other measures were: Friedreich Ataxia Rating Scale (FARS) and Nine Hole Peg Test (NHPT). Furthermore, we used the 6 Minute Walk Test (6MWT), the Timed Up and Go (TUG) and the Berg Balance Scale (BBS) only on ambulant subjects. Outcomes were evaluated at baseline and at the end of the treatment. Results: We report that the IR significantly improves motor performance and ataxia symptoms in patients with FRDA. Our study shows significant functional improvement in all the outcome measures used, except for NHPT bilaterally. FARS and SARA scores post-IR are significatively reduced when compared (p < 0.001). Discussion: We demonstrate that IR programs in FRDA can provide a meaningful clinical improvement in terms of outcome measures. These findings could be useful when approaching progressive neurological disorders.

Cerebrovascular reactivity to carbon dioxide tension in newborns: data from combined time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy.

Significance: Critically ill newborns are at risk of brain damage from cerebrovascular disturbances. A cerebral hemodynamic monitoring system would have the potential role to guide targeted intervention. Aim: To obtain, in a population of newborn infants, simultaneous near-infrared spectroscopy (NIRS)-based estimates of cerebral tissue oxygen saturation (StO2) and blood flow during variations of carbon dioxide tension (pCO2) levels within physiologic values up to moderate permissive hypercapnia, and to examine if the derived estimate of metabolic rate of oxygen would stay constant, during the same variations. Approach: We enrolled clinically stable mechanically ventilated newborns at postnatal age >24 h without brain abnormalities at ultrasound. StO2 and blood flow index were measured using a non-invasive device (BabyLux), which combine time-resolved NIRS and diffuse-correlation spectroscopy. The effect of changes in transcutaneous pCO2 on StO2, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen index (tCMRO2i) were estimated. Results: Ten babies were enrolled and three were excluded. Median GA at enrollment was 39 weeks and median weight 2720 g. StO2 increased 0.58% (95% CI 0.55; 0.61, p<0.001), CBF 2% (1.9; 2.3, p<0.001), and tCMRO2 0.3% (0.05; 0.46, p=0.017) per mmHg increase in pCO2. Conclusions: BabyLux device detected pCO2-induced changes in cerebral StO2 and CBF, as expected. The small statistically significant positive relationship between pCO2 and tCMRO2i variation is not considered clinically relevant and we are inclined to consider it as an artifact.

Dose-dependent impact of human milk feeding on tidal breathing flow-volume loop parameters across the first 2 years of life in extremely low-birth-weight infants: a cohort study.

The purpose of this study is to test the hypothesis that higher consumption of human milk (HM) in preterm infants with birth weight (BW) <1000 g is associated with improved lung function in a dose-dependent manner over the first 2 years of corrected age (CA). This retrospective study at an academic medical center included infants with BW <1000g. They had lung function assessment by the tidal breathing flow-volume loop (TBFVL) follow-up visits at 0-3-, 3-6-, 6-12-, 12-18-, and 18-24-month CA. One hundred eighty infants were included in the study with a mean (SD) gestational age 26.5 (1.90) weeks and BW 772.4 (147.0) g, 50% were female, and 60% developed BPD. 62.8% of infants received HM during the NICU stay. According to a general linear model (including GA, being small for GA (SGA), sex, human milk percentage, sepsis, and BPD), on average, each week of GA resulted in a higher tPTEF/tE of 1.24 (p = 0.039) and being SGA in a lower tPTEF/tE of 5.75 (p = 0.013) at 0-3-month CA. A higher percentage of human milk out of the total enteral intake was associated with better tPTEF/tE z-scores at 0-3 months (p = 0.004) and 18-24 months of CA (p = 0.041). BPD diagnosis was associated with a relevantly worse tPTEF/tE z-score at 6-12 months of CA (p = 0.003). CONCLUSION: Preterm infants with higher consumption of HM had significantly less airway obstruction across the first 2 years, suggesting that human milk may contribute in a dose-dependent manner to improve lung function in early childhood in former preterm infants born ELBW. WHAT IS KNOWN: • Human milk feeding reduces the risk of prematurity-related morbidities, including necrotizing enterocolitis, sepsis, lower respiratory tract infections, and BPD. Both exclusive and partial human milk feeding appear to be associated with a lower risk of BPD in preterm infants. WHAT IS NEW: • This cohort study of 180 preterm infants with birth weight < 1000 g found that exposure to human milk during hospitalization improves airway obstruction markers tPTEF/tE z-score over the first 2 years of corrected age in a dose-dependent manner.

To be born twin: effects on long-term neurodevelopment of very preterm infants-a cohort study.

Objective: To examine the effect of twin birth on long-term neurodevelopmental outcomes in a cohort of Italian preterm infants with very low birth weight. Study design: We performed a retrospective cohort study on children born in a tertiary care centre. We included children born between 1 January 2007 and 31 December 2013 with a gestational age (GA) of ≤32 weeks and birth weight of <1,500 g. The infants born from twin pregnancies complicated by twin-to-twin transfusion syndrome and from higher-order multiple pregnancies were excluded. The children were evaluated both at 2 years corrected age and 5 years chronological age with Griffiths mental development scales revised (GMDS-R). The linear mixed effects models were used to study the effect of being a twin vs. being a singleton on GMDS-R scores, adjusting for GA, being born small for gestational age, sex, length of NICU stay, socio-economic status, and comorbidity score (CS) calculated as the sum of the weights associated with each of the major morbidities of the infants. Results: A total of 301 children were included in the study, of which 189 (62.8%) were singletons and 112 (37.2%) were twins; 23 out of 112 twins were monochorionic (MC). No statistically significant differences were observed between twins and singletons in terms of mean general quotient and subscales at both 2 and 5 years. No effect of chorionicity was found when comparing scores of MC and dichorionic twins vs. singletons; however, after adjusting for the CS, the MC twins showed lower scores in the hearing and language and performance subscales at 5 years. Conclusion: Overall, in our cohort of children born very preterm, twin infants were not at higher risk of neurodevelopmental impairment compared with singletons at pre-school age.

Comparative efficacy of three Bayesian variable selection methods in the context of weight loss in obese women.

The use of high-dimensional data has expanded in many fields, including in clinical research, thus making variable selection methods increasingly important compared to traditional statistical approaches. The work aims to compare the performance of three supervised Bayesian variable selection methods to detect the most important predictors among a high-dimensional set of variables and to provide useful and practical guidelines of their use. We assessed the variable selection ability of: (1) Bayesian Kernel Machine Regression (BKMR), (2) Bayesian Semiparametric Regression (BSR), and (3) Bayesian Least Absolute Shrinkage and Selection Operator (BLASSO) regression on simulated data of different dimensions and under three scenarios with disparate predictor-response relationships and correlations among predictors. This is the first study describing when one model should be preferred over the others and when methods achieve comparable results. BKMR outperformed all other models with small synthetic datasets. BSR was strongly dependent on the choice of its own intrinsic parameter, but its performance was comparable to BKMR with large datasets. BLASSO should be preferred only when it is reasonable to hypothesise the absence of synergies between predictors and the presence of monotonous predictor-outcome relationships. Finally, we applied the models to a real case study and assessed the relationships among anthropometric, biochemical, metabolic, cardiovascular, and inflammatory variables with weight loss in 755 hospitalised obese women from the Follow Up OBese patients at AUXOlogico institute (FUOBAUXO) cohort.

Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry.

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease. METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

In-hospital growth and long-term neurodevelopmental outcomes of very low birth weight infants.

Background and Objectives: Very low birth weight infants (VLBW) are at risk for adverse growth and neurodevelopmental outcomes. We aimed to evaluate the association between growth during Neonatal Intensive Care Unit (NICU) stay and long-term neurodevelopmental outcomes in a cohort of preterm VLBW newborns. Methods: We conducted a longitudinal observational study in the Follow-up Service of our Clinic from January 2014 to April 2017. All preterm VLBW infants born at our hospital and enrolled in our follow-up program were considered eligible for the study. The neurodevelopmental assessment was performed using the Griffiths Mental Development Scales at 12 and 24 months corrected age. Results: Study population included 172 subjects (47.1% males) with a mean gestational age of 29 weeks and a mean birth weight of 1,117 g. A unitarian Δz-score increase in head circumference from birth to discharge was associated with a 1.6-point increase in General Quotient at 24 months corrected age. An association with subscales C and D was also found. Likewise, an increase in length Δz-score was associated with better 24-month subscale C scores although not reaching statistical significance. No relationship with the outcome at 24 months was found for weight gain. Conclusions: Growth during NICU stay appears to be related to a more favorable neurodevelopmental outcome at 24 months corrected age, especially in the hearing and language domain (subscale C). The longitudinal evaluation of auxological parameters during hospitalization can contribute to the identification of subjects at risk for adverse neurodevelopmental outcomes in the first years of life.

Pooling Strategies to Modify Macronutrient Content of Pasteurized Donor Human Milk.

Background: Donor human milk (DHM) is the recommended feeding for preterm infants when mother's own milk is unavailable or insufficient. DHM macronutrient's variability may have significant implications on preterm growth. Different pooling strategies could be used to improve the macronutrient content, facilitating the achievement of nutritional requirements of preterm. Objective: The aim was to compare the impact of random pooling (RP) and target pooling (TP) strategies on the macronutrient content of DHM and to identify which RP practice allows the achievement of a macronutrient composition as similar as possible to that achievable with TP. Methods: The macronutrient content of 1,169 single-donor pools was analyzed, and a TP strategy combining 2,3,4, or 5 single-donor pools was adopted. On the bases of single-donor pools' analyses, a simulation of 10,000 randomly selected pools for each configuration of donor considered and for different milk volume proportions was performed. Results: Regardless of the type of strategy and milk volume, as the number of donor per pool increases, the percentage of pools with a macronutrient content equal or higher than the reference values for human milk increases. Conclusion: When a TP strategy is not feasible, a RP strategy combining at least five donors should be performed to obtain a better macronutrient content of DHM.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

Hospital-acquired skin lesions in the neonatal intensive care unit: A retrospective analysis of temporal trends and quality improvement strategies.

PURPOSE: Skin lesions in neonatal population are an emerging problem deserving attention from health care professionals. The purpose of this study is to retrospectively assess the incidence of hospital-acquired skin lesions during a 6-year period and to describe the characteristics of infants who developed them. DESIGN AND METHODS: This was a retrospective observational study conducted in a university-tertiary care center between 2015 and 2020. A descriptive analysis of the observed skin lesions is presented according to 2 time periods: 1) the implementation phase of a quality improvement program (2015-2019) and 2) the postimplementation phase (2020). RESULTS: Our findings showed an apparent increase in the incidence of all reported skin lesions throughout the study period. Pressure injuries were the most frequently reported skin lesions showing an increasing incidence over time which, however, was paralleled by a reduction in their severity. Among pressure injuries, device-related injuries were the most commonly observed (56.6% and 62.5% in the two periods, respectively) with nasal continuous positive airway pressure-related injuries accounting for 71.7% and 56.0% of lesions, respectively, and mainly affecting the nose root. The occipital area was the most frequently involved site in cases of conventional pressure injuries. CONCLUSION: Infants admitted to Neonatal Intensive Care Units may be at high risk of developing skin lesions. The adoption of appropriate preventative as well as treatment interventions could be effective in reducing the severity of pressure injuries. PRACTICE IMPLICATIONS: The implementation of quality improvement strategies may contribute to prevent skin injuries or lead to their early detection.

Neonatal intestinal failure: Growth pattern and nutrition intakes in accordance with weaning from parenteral nutrition.

BACKGROUND: Short bowel syndrome is the most common cause of intestinal failure (IF) in infants. We aimed to evaluate growth, nutrition intakes, and predictors of weaning from parenteral nutrition (PN) of infants with IF. METHODS: Clinical parameters, nutrition intakes, body weight and length z-scores were compared monthly from the 1st to 12th and at 18 and 24 months among infants receiving PN and those weaned. Logistic regression analysis was conducted to explore the predictors of weaning. RESULTS: We included 23 infants (10/23 weaned). Median [range: minimum; maximum] birth weight and gestational age were 1620 [590; 3490] g and 31 [24; 39] weeks, respectively. All infants showed growth retardation with similar median delta weight z-score from birth to discharge: -1.48 [-1.92; -0.94] in not-weaned and -1.18 [-2.70; 0.31] in weaned infants (P = 0.833) and a subsequent regain after the discharge: 0.20 [-3.47; 3.25] and 0.84 [-0.03; 2.58], respectively (P = 0.518). No differences in length z-score were found. After the sixth month, infants weaned from PN received lower PN energy and protein intakes compared with those not-weaned. Infants weaned from PN showed lower PN dependency index (PNDI%) from 5 months onward (45% for weaned and 113% for not-weaned infants at 5 months: P < 0.001). The Belza score, a predictor of enteral autonomy computed at 6 months, is associated with being weaned from PN within 24 months (odds ratio: 1.906; P = 0.039). CONCLUSION: Infants weaned and not-weaned showed similar growth patterns. Our findings support the clinical relevance of Belza score and PNDI% as predictors of weaning from PN.

Comparative Analysis of Docosahexaenoic Acid (DHA) Content in Mother's Milk of Term and Preterm Mothers.

Objectives and Study: Docosahexaenoic acid (DHA) plays an essential role in infants' development. Maternal diet and breastmilk are the primary DHA sources for newborns. This single-center observational study aimed to compare the DHA content in mother's milk of preterm mothers with that of term ones, and to investigate the changes in mother's milk DHA content according to the week of the gestational age. Methods: A food frequency questionnaire (FFQ) was submitted to each mother to estimate the DHA intake during the last trimester of pregnancy, and the mother's milk was collected between 24 and 96 h post-partum. Results: Women who gave birth prematurely showed a lower content of mother's milk DHA than the term ones (0.51; IQR 0.38−0.6% FA vs. 0.71; IQR 0.52−0.95% FA; p = 0.001). In the multivariate linear regression analyses, for each additional week of gestational age, there was an increase in DHA content in the mother's milk (0.046% FA; CI 95% 0.018−0.074; p < 0.001). Conclusions: Our results suggest that breast milk may not be sufficient to fully satisfy the recommended DHA intake in preterm infants. This study may represent a starting point to investigate new possible DHA supplementation strategies, especially for the late and moderate preterm infants.

Don't Forget the Bones: Incidence and Risk Factors of Metabolic Bone Disease in a Cohort of Preterm Infants.

Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

Development of a new scoring method in the neurofunctional assessment of preterm infants.

Infants born preterm are at high risk of presenting neurodevelopmental delay. The Neurofunctional Assessment (NFA) describes infants' neurodevelopment through the evaluation of six different domains. This study aimed to evaluate how, in a cohort of preterm infants, each NFA domain assessed at 3 months of corrected age (CA) was associated with neurodevelopment at 2 years of CA using the Griffiths Mental Developmental Scales Extended Revised (GMDS-ER). In addition, by introducing the NFA complexity score (CS), the study aimed to define a threshold that can help clinicians discriminate infants at higher risk of later neurodevelopmental delay. We conducted an observational, longitudinal study including 211 preterm infants. At 3 months of CA, infants who had normal scores in each domain showed a significantly higher GMDS-ER global quotient (GQ) at 2 years of CA. In addition, linear model results showed a significant negative relationship between the NFA CS and 2-year GMDS-ER GQ (estimate: - 0.27; 95% CI - 0.35, - 0.20; p value < 0.001). Each 10-point increase in the NFA CS was associated with an average 2.7-point decrease in the GMDS GQ. These results highlight how the NFA domains and NFA CS are compelling instruments for the early identification of children at risk for long-term adverse outcomes.

Hemostatic Evaluation With Viscoelastic Coagulation Monitor: A Nicu Experience.

Background: Viscoelastic coagulation tests provide valuable information in neonatal intensive care units (NICUs), but the lack of reference intervals still limits their decision-making power according to gestational age. The aim of the present study is to evaluate the hemostasis of a cohort of full-term (FT) and late-preterm (LP) infants using the viscoelastic coagulation monitor (VCM®) system, a new portable device that uses untreated whole blood. Methods: An observational study was performed to identify non-coagulopathic FT and LP infants admitted to III° level NICU (January 2020 to December 2021) with a VCM test in the first 72 h of life. Results: Forty-five patients were enrolled, 26 FT and 19 LP. No statistical differences in hemostatic parameters were observed between FT and LP nor between stable and unstable neonates. Clotting time (CT) was positive correlated with PT (p = 0.032), not with aPTT (p = 0.185). From linear regression, platelet resulted associated with: clot formation time (CTF, p = 0.003), alpha angle (Alpha, p = 0.010), amplitude at 10 (A10, p = 0.001), amplitude at 20 min (A20, p < 0.001), maximum clot firmness (MCF, p < 0.001); and fibrinogen was associated with: A10 (p = 0.008), A20 (p = 0.015) and MCF (p = 0.024). Compared to the adult reference population, neonates showed shorter CT (mean (SD): 5.3 (1.4) vs. 7.0 (0.9) min, p < 0.001), CFT (2.4 (0.7) vs. 2.8 (0.6) minutes, p < 0.001) and higher Alpha (60.8 (6.3) vs. 55 (5)°, p < 0.001). In addition, the neonatal cohort showed an early transient difference in amplitude and fibrinolysis, as follows: A10 (28.0 (5.0) vs. 26 (4) VCM units, p =0.004), A20 (34.8 (5.0) vs. 33 (4) VCM units, p =0.012), and LI30 (99.8 (0.5) vs. 99 (1)%, p <0.001). Conclusions: The viscoelastic profile of FT and LP infants assessed with VCM showed a hemostatic competence characterized by accelerated coagulation and clot formation time, in line with other viscoelastic techniques. VCM system provides promising applications in the NICU setting.

Proinflammatory Endothelial Phenotype in Very Preterm Infants: A Pilot Study.

Very preterm infants are exposed to prenatal inflammatory processes and early postnatal hemodynamic and respiratory complications, but limited data are available about the endothelial effect of these conditions. The present pilot study investigates the perinatal endothelial phenotype in very preterm infants (VPIs) and explores its predictive value on neonatal mortality and hemodynamic and respiratory complications. Angiopoietin 1 (Ang-1), Ang-2, E-selectin, vascular adhesion molecule 1 (VCAM-1), tissue factor (TF), and endothelin 1 (ET-1) concentrations were tested in first (T1), 3rd (T2), and 7-10th (T3) day of life in 20 VPIs using Luminex technology and compared with 14 healthy full-term infants (FTIs). Compared to FTIs, VPIs had lower Ang-1 at T1 and T2; higher Ang-2 at T1, T2, and T3; higher Ang-2/Ang-1 ratio at T1, T2, and T3; lower E-selectin at T1, T2, and T3; higher VCAM-1 at T1; higher TF at T2. No differences in concentrations were found in neonatal deaths. VPIs with hemodynamic or respiratory complications had higher Ang-2 at T3. Perinatal low Ang-1 and high Ang-2 associated with high VCAM-1 and TF in VPIs suggest a proinflammatory endothelial phenotype, resulting from the synergy of a pathological prenatal inheritance and a premature extrauterine transition.