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The therapeutic armamentarium in Multiple Sclerosis (MS) has increased considerably during the past years. Neurologists often face dilemmas in their effort to select the proper therapeutic agent. Considering the long-lasting experience and well-established profile of safety, interferon-ß is thought to be the first choice of treatment for clinically isolated syndrome and first-diagnosed remitting relapsing MS. The administration of interferon-ß and glatiramer acetate has been proven to reduce disease relapses and lesion load in MRI T2-images as well as the number of enhancing lesions after gadolinium administration. The effect of interferon-ß in disability progression and cognitive impairment is still under debate. Natalizumab, fingolimod and in resistant cases mitoxantrone are considered second line treatments for MS. The administration of the monoclonic antibody natalizumabhas been used for several years with satisfactory results.. However regular tests for detection of antibodies against virus JC are required during treatment due to the increased incidence of PML. Fingolimod is the first approved oral disease-modyfing agent. Recent clinical trials focus on the side effects of fingolimond. The most common are heart rate disorders, ophthalmologic complications, infections, liver enzyme elevation and lymphopenia. Finally fampridine and BG-12 are recent additions in the therapeutic choices of MS. Further use of these agents in the future will determine their efficacy and safety. [ABSTRACT FROM AUTHOR]

Objective: This post-hoc analysis of data extracted from a prospective study aimed to explore for the first time if the efficacy of fremanezumab in preventing difficult-to-treat migraine, according to ICHD-III, would differ between pre-menopausal and post-menopausal women., Methods: A total of 171 (aged 18-70 years) fremanezumab-treated female migraine patients for six consecutive months were classified to those at pre-menopausal ( n  = 82) or post-menopausal ( n  = 89). Monthly headache days (MHD), disability, and quality of life (QOL) outcomes were assessed at baseline and at week 24 post-fremanezumab within subgroups and were then compared between them. Safety and tolerability were also assessed., Results: In both groups, fremanezumab demonstrated significant reductions in MHDs, reduced disability, and higher QOL scores at week 24 post-treatment, compared to baseline. However, the between-subgroup comparison documented that pre-menopausal women and those at post-menopausal comparably benefited with significant reductions in overall MHDs ( p  = 0.883). Less disability, according to MIDAS ( p  = 0.696) and HIT-6 scores ( p  = 0.912), as well as higher QOL scores at week 24 post-fremanezumab, were also comparably evident in both groups. Safety was excellent across both subgroups., Conclusion: Fremanezumab can be considered a very effective treatment option for preventing migraines in difficult-to-treat women, aged 18-70 years, regardless of their menopausal status.

We intend to evaluate the association of intact Fibroblast Growth Factor 23 (i-FGF23), a phosphaturic hormone that contributes to anemia of inflammation, with markers of iron homeostasis, inflammation, and bone mineral metabolism in acute pediatric infections. Seventy-nine children, aged 1 month-13 years, out of which forty-two were males and thirty-seven females, participated in this study. Children with diseases and nutrient deficiencies causing anemia were excluded. Twenty-six patients had bacterial infections, twenty-six had viral infections, and twenty-seven children served as healthy controls. Complete blood count, markers of inflammation, iron and mineral metabolism, serum hepcidin, and i-FGF23 were compared between the groups. Thirty-nine percent of patients with bacterial infection and twelve percent of patients with viral infection presented characteristics of anemia of inflammation ( p < 0.001). Ninety-two percent of patients with bacterial infection and eighty-one percent of patients with viral infection had functional iron deficiency ( p < 0.001). Hepcidin was significantly positively correlated with the duration of fever, markers of inflammation, and negatively with iron, mineral metabolism parameters, and i-FGF23. i-FGF23 was positively correlated with iron metabolism parameters and negatively with the duration of fever, markers of inflammation, and hepcidin. Hepcidin levels increase, whereas i-FGF23 levels decrease in acute pediatric infections. Further research is required to understand the role of FGF23 in the hepcidin-ferroportin axis and for hepcidin in the diagnosis of bacterial infections and mineral metabolism.

Background: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important., Design and Methods: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used., Results: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.

Background: The safety of the anesthesia team model performed in oral and maxillofacial surgery (OMS) offices has been criticized by professional and mainstream media., Purpose: This study aims to assess the incidence of adverse anesthetic events (AEs) associated with the OMS anesthesia team model and identify risk factors associated with AEs., Study Design, Setting, Sample: This was a retrospective cohort study utilizing a patient database from Paradigm Oral Health, Lincoln, Nebraska, a managed service organization (MSO). Subjects included were 14 and older, undergoing open-airway intravenous anesthesia for ambulatory OMS procedures using the OMS anesthesia team model at multiple private practices in the MSO network between June 30, 2010, and September 30, 2022. Exclusion criteria included patients younger than 14 or patients with incomplete medical records., Predictor Variable: Primary predictor variables were age, sex, American Society of Anesthesiologists physical status classification system (ASA) score, type of surgical procedure performed, and the types of medications administered during sedation., Main Outcome Variable(s): The presence of an AE. The definition of an AE was modeled on the World Society of Intravenous Anesthesia definition. All AEs were identified through surrogate markers, which were identified through chart review. One example of an AE is ventricular fibrillation, which necessitates the application of medications; here the medication is the surrogate marker., Covariates: None., Analyses: The data were analyzed using t-tests and χ 2 tests. P values ≤ .05 were considered statistically significant., Results: Included in the study were 61,237 sedation cases (53.87% female and 46.13% male), for 56,076 unique patients ranging from 14 to 98 years of age (mean 33.26 ± 18.35). An AE incidence of 3 per 100,000 per year (25 total events) was observed. Neither age, sex, ASA score, nor type of surgical procedure exhibited statistically significant associations with AEs. A statistically significant association was found between AEs and fentanyl (P = .0008)., Conclusion and Relevance: This investigation shows a smaller incidence of AEs than previous studies of the OMS anesthesia team model., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Bioinformatics is a scientific field that uses computer technology to gather, store, analyze, and share biological data and information. DNA sequences of genes or entire genomes, protein amino acid sequences, nucleic acid, and protein-nucleic acid complex structures are examples of traditional bioinformatics data. Moreover, proteomics, the distribution of proteins in cells, interactomics, the patterns of interactions between proteins and nucleic acids, and metabolomics, the types and patterns of small-molecule transformations by the biochemical pathways in cells, are further data streams. Currently, the objectives of bioinformatics are integrative, focusing on how various data combinations might be utilized to comprehend organisms and diseases. Bioinformatic techniques have become popular as novel instruments for examining the fundamental mechanisms behind neonatal diseases. In the first few weeks of newborn life, these methods can be utilized in conjunction with clinical data to identify the most vulnerable neonates and to gain a better understanding of certain mortalities, including respiratory distress, bronchopulmonary dysplasia, sepsis, or inborn errors of metabolism. In the current study, we performed a literature review to summarize the current application of bioinformatics in neonatal medicine. Our aim was to provide evidence that could supply novel insights into the underlying mechanism of neonatal pathophysiology and could be used as an early diagnostic tool in neonatal care.

Background: Evidence examining the association of over-hydration during early life with hemodynamically significant patent ductus arteriosus (hsPDA) and other morbidities is limited. Our aim was to evaluate the association of fluid overload during the first postnatal day with hsPDA and common neonatal morbidities such as bronchopulmonary dysplasia in preterm infants., Methods: A retrospective cohort study was conducted enrolling infants ≤30 weeks' gestation and ≤1500 grams' birth weight, admitted to a tertiary Neonatal Unit. We calculated the fluid balance, and we estimated the incidence of infants with fluid overload ≥5% during the first postnatal day, evaluating any possible correlation with hsPDA., Results: One hundred three infants of 27.3±1.6 weeks' gestation and 1009±225 grams' birth weight were enrolled, of whom 32 (31%) were diagnosed with HsPDA. Fluid overload during the first postnatal day was recorded in 42 infants (41%). Infants with fluid overload were diagnosed with hsPDA in 48%, compared to 20% of infants without fluid overload (P=0.004). No differences were recorded in the development of bronchopulmonary dysplasia or survival. Fluid overload of ≥5% was significantly correlated with hsPDA (r=0.37, P=0.003) and had an independent contribution to the risk of hsPDA (OR=1.17, 95% CI: 1.05-1.58), irrespective of other perinatal factors., Conclusions: In preterm infants, fluid overload ≥5% is significantly associated with hsPDA; therefore, fluid management during the first postnatal day should be closely regulated.

Objective: We examined the impact of perinatal factors on cord serum club cell protein (CC16) and the association of CC16 with mechanical ventilation and bronchopulmonary dysplasia (BPD) in preterm neonates., Study Design: A retrospective cohort study including 60 neonates born with gestational age (GA) < 34 weeks. The impact of categorical perinatal factors on cord blood levels of CC16 was examined with univariate and multivariate regression analyses., Results: In neonates with GA < 32 weeks, cord blood CC16 concentrations were significantly lower compared to neonates with GA between 32 0/7 and 33 6/7 weeks (5.4 ± 2.5 compared to 7.6 ± 2.9 ng/mL, p  = 0.039). Neonates with prolonged rupture of membranes had significantly lower CC16 compared to those without prolonged rupture of membranes (4.0 ± 1.9 compared to 7.2 ± 2.2, p  < 0.001). Finally, neonates with BPD had significantly lower CC16, compared to neonates without BPD (4.2 ± 2.1 compared to 7.0 ± 2.2 ng/mL, p  = 0.004).Prolonged rupture of membranes was significantly negatively associated with CC16 (b = -2.67, 95% confidence interval [CI] -0.49 to -4.85, p  = 0.017), after adjusting for GA (b = 0.23, 95% CI 0.03-0.42, p  = 0.022), mode of conception, and mode of delivery. Finally, higher CC16 levels were significantly inversely associated with BPD (odds ratio = 0.33, 95% CI 0.12-0.88, p  = 0.028), after adjusting for GA (b = 0.27, 95% CI 0.09-0.78, p  = 0.015), and birth weight., Conclusion: Prolonged rupture of membranes was significantly negatively associated with cord serum CC16, after adjusting for GA, conception, and delivery mode, and CC16 was significantly inversely associated with BPD, after adjusting for GA and birth weight., Key Points: · Neonates with prolonged rupture of membranes had lower CC16 levels.. · CC16 was significantly negatively associated with BPD.. · CC16 could be a biomarker of lung injury and BPD.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs. Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7-100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process. Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology.

Context: In utero exposure to maternal obesity or diabetes is considered a pro-inflammatory state., Objective: To evaluate whether cord blood proprotein convertase subtilisin/kexin-type 9 (PCSK9), which is regulated by inflammation and metabolic derangements, is elevated in neonates born to overweight, obese, or diabetic mothers., Methods: A retrospective study in full-term neonates born between 2010 and 2023, at Brigham and Women's Hospital. There were 116 neonates included in our study, of which 74 (64%) were born to overweight/obese mothers and 42 (36%) were born to nonoverweight/nonobese mothers., Results: Neonates born to overweight/obese mothers had significantly higher cord blood concentrations of PCSK9 compared with neonates born to nonoverweight/nonobese group (323 [253-442] ng/mL compared with 270 [244-382] ng/mL, P = .041). We found no significant difference in cord blood concentrations of PCSK9 between neonates of diabetic mothers compared with neonates of nondiabetic mothers. In multivariate linear regression analysis, higher cord plasma PCSK9 concentration was significantly associated with maternal overweight/obesity status (b = 50.12; 95% CI, 4.02-96.22; P = .033), after adjusting for gestational age, birth weight, male sex, and intrauterine growth restriction., Conclusion: Neonates born to mothers with overweight/obesity have higher cord blood PCSK9 concentrations compared with the nonoverweight/nonobese group, and higher cord blood PCSK9 concentrations were significantly associated with maternal overweight/obesity status, after adjusting for perinatal factors. Larger longitudinal studies are needed to examine the role of PCSK9 in the development of metabolic syndrome in high-risk neonates born to overweight, obese, or diabetic mothers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Minimal invasive surfactant therapy (MIST) includes the tracheal instillation of surfactant via a thin catheter for the treatment of preterm infants with respiratory distress syndrome (RDS). We aimed to evaluate the impact of MIST compared to intubation, surfactant, extubation (INSURE) technique on respiratory outcomes., Methods: A prospectively recruited cohort of preterm infants ≤32 weeks with RDS was compared against a historical cohort of infants treated with INSURE. The primary outcome was the need for mechanical ventilation within 72 hours of age and secondary outcomes the overall need and duration of mechanical ventilation, the development of bronchopulmonary dysplasia, common morbidities, and survival., Results: Thirty-six infants treated with MIST of 29.1±2.2 weeks' gestation and 1219±238 g birthweight compared against 37 infants of 28.8±2.3 weeks' gestation and 1195±336 g birthweight treated with INSURE. A lower proportion of infants treated with MIST required mechanical ventilation within 72 hours of age compared to those treated with INSURE (11% compared 32%, P=0.042). However, no significant differences were noted regarding the overall intubation incidence, bronchopulmonary dysplasia, other morbidities, or survival., Conclusions: In spontaneously breathing infants ≤32 weeks with RDS, the MIST technique was associated with a lower need for intubation within 72 hours of age, but otherwise with no significant differences regarding BPD or other neonatal morbidities.

Objective: To identify variables associated with extubation success in extremely preterm neonates extubated from invasive volume-targeted ventilation., Study Design: We retrospectively evaluated 84 neonates ≤28 weeks' gestational age, on their first elective extubation. The primary outcome of successful extubation was defined as non-reintubation within seven days. We used multivariate logistic regression analysis., Results: We identified 58 (69%) neonates (mean gestational age of 26.5 ± 1.4 weeks, birthweight 921 ± 217 g) who met the primary outcome. Female sex (OR 1.15, 95% CI 1.01-9.10), higher pre-extubation weight (OR 1.29, 95% CI 1.05-1.59), and pH (OR 2.54, 95% CI 1.54-4.19), and lower pre-extubation mean airway pressure (MAP) (OR 0.49, 95% CI 0.33-0.73) were associated with successful extubation., Conclusions: In preterm neonates, female sex, higher pre-extubation weight and pH, and lower pre-extubation MAP were predictors of successful extubation from volume-targeted ventilation. Evaluation of these variables will likely assist clinicians in selecting the optimal time for extubation in such vulnerable neonates., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aim: To investigate the routine guidance provided by pediatricians concerning the timing of complementary feeding (CF) for both healthy infants and those at a heightened risk of allergies., Methods: A total of 233 pediatricians participated in an anonymous online survey that included questions about demographics and recommendations for CF. Specifically, they provided guidance on the types of foods, preparation methods, supplements, time intervals for introducing new foods to infants at low and high allergy risk, and delayed food introductions for high-risk cases., Results: The respondents advised introducing certain foods at specific ages: fruits, starchy non-gluten grains, vegetables, olive oil, and meat were appropriate at 6 months; gluten-rich grains at 7 months; yogurt, hard-boiled eggs, and legumes at 8 months; fish at 8.5 months; and nuts at 9 months. Pediatricians, especially those with less than 15 years of practice, often introduced egg, seafood, gluten-rich grains, legumes, and nuts earlier for high-risk infants. Parenthood and male gender were associated with the earlier introduction of eggs and grains., Conclusions: Greek pediatricians follow a structured food introduction schedule for CF in infants. Interestingly, they tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants. Key Notes: Despite recent evidence-based indications on healthy complementary feeding strategies for infants, discrepancies persist among pediatricians regarding food choices and the order and timing of food introduction, both for healthy infants and those at risk of allergy. Guidance on complementary feeding by pediatricians is influenced by their individual characteristics. Pediatricians tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants.

Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Conclusions: Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.

Objectives: To examine whether first-intention high-frequency jet ventilation (HFVJ), compared to volume-targeted ventilation (VTV), in extremely preterm infants is associated with lower incidence of bronchopulmonary dysplasia (BPD) and other adverse clinical outcomes., Study Design: We conducted a retrospective cohort study evaluating neonates with gestational age (GA) ≤28 weeks, who received first-intention HFJV (main exposure) or VTV (comparator), between 11/2020 and 3/2023, with a subgroup analysis including neonates with GA ≤26 weeks and oxygenation index (OI) >5., Results: We identified 117 extremely preterm neonates, 24 (GA 25.2 ± 1.6 weeks) on HFJV, and 93 (GA 26.4 ± 1.5 weeks, p  = 0.001) on VTV. The neonates in the HFJV group had higher oxygenation indices on admission, higher inotrope use, and remained intubated for a longer period. Despite these differences, there were no statistically significant differences in rates of BPD, survival, or other adverse outcomes between the two groups. In subgroup analysis of 18 neonates on HFJV and 39 neonates on VTV, no differences were recorded in the GA, and duration of mechanical ventilation, while neonates in the HFJV group had significantly lower rates of BPD (50% compared to 83%, p  = 0.034), and no significant differences in other adverse outcomes compared to neonates in the VTV group. In neonates ≤26 weeks of GA with OI >5, HFJV was significantly associated with lower rates of BPD (OR 0.21, 95% CI 0.05-0.92), and combined BPD or death (OR 0.18, 95% CI 0.03-0.85), after adjusting for birth weight, and Arterial-alveolar gradient on admission., Conclusions: In extremely preterm neonates ≤26 weeks of GA with OI >5, first-intention HFJV, in comparison to VTV, is associated with lower rates of BPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Rallis, Ben-David, Woo, Robinson, Beadles, Bernardini, Abdulhayoglu, Flanigan and Christou.)

Background: Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies., Methods: Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital., Results: Maternal smoking during pregnancy ( p = 0.001) and an older sibling atopy history ( p = 0.03) was significantly linked to AD incidence. Cesarean section delivery ( p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD ( p = 0.01), and food elimination without medical guidance ( p = 0.02) due to AD correlated with an elevated risk of food allergies., Conclusions: Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies.

Objective: Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9), a modulator of low-density lipoprotein (LDL) cholesterol metabolism, has been reported to be a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. In the current study, we sought to investigate potential differences in serum PCSK9 levels between infants with deviant birth weight and controls., Methods: We enrolled 82 infants, classified into 33 small (SGA), 32 appropriate (AGA), and 17 large for gestation (LGA) infants. Serum PCSK9 was measured on routine blood analysis within the first postnatal 48 h., Results: PCSK9 was significantly higher in SGA as compared to AGA and LGA infants [322 (236-431) as compared to 263 (217-302) and 218 (194-291) ng/ml respectively, p  = .011]. In comparison to term AGA infants, PCSK9 was significantly elevated in preterm AGA and SGA infants. We also found a significantly higher level of PCSK9 in term female SGA infants as compared to term male SGA infants [325 (293-377) as compared to 174 (163-216) ng/ml, p  = .011]. PCSK9 was significantly correlated with gestational age ( R  = -0.404, p  < .001), birth weight ( R  = -0.419, p  < .001), total cholesterol ( R  = 0.248, p  = .028) and LDL cholesterol ( R  = 0.370, p  = .001). SGA status (OR 2.56, p  = .004, 95% CI 1.83-4.28) and prematurity (OR 3.10, p  = .001, 95% CI 1.39-4.82) were strongly related to serum PCSK9 levels., Conclusion: PCSK9 levels were significantly associated with total and LDL cholesterol. Moreover, PCSK9 levels were higher in preterm and SGA infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.Highlights What's already known? Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9) is a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. Infants that were born with a deviant birth weight have a unique lipoprotein metabolism profile. What this study adds? Serum PCSK9 levels were significantly associated with total and LDL cholesterol. PCSK9 levels were higher in preterm and small for gestation infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.

Postnatal growth failure, a common problem in very preterm neonates associated with adverse neurodevelopmental outcome, has recently been shown not to be inevitable. There is a wide discussion regarding feeding practices of very preterm neonates, specifically regarding feeding volumes and nutrients supply to avoid postnatal growth failure. Current guidelines recommend an energy intake of 115–140 kcal /kg per d with a considerably higher upper limit of 160 kcal/kg per d. The feeding volume corresponding to this energy supply is not higher than 200 ml/kg in most cases. From the other side, randomised and observational studies used higher feeding volumes, and these were associated with better weight gain and growth, while no complications were noted. Taking into account the above, nutritional practices should be individualised in each very and extremely preterm infant trying to reduce postnatal growth failure, pointing out that available data are inconclusive regarding the effect of high-volume feeds on growth. Large clinical trials are necessary to conclude in the best feeding practices of very preterm neonates.

The role of postnatal Doppler measurements of the superior mesenteric artery (SMA) in detecting neonates at risk of necrotizing enterocolitis (NEC) remains uncertain; therefore, we systematically reviewed and meta-analyzed the existing evidence regarding the usefulness of SMA Doppler measurements in detecting neonates at risk for NEC. We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and we included studies which reported the following Doppler ultrasonography indices: peak systolic velocity, end-diastolic velocity, time average mean velocity, differential velocity, pulsatility index (PI) and resistive index. Eight studies were eligible for inclusion in the meta-analysis. Evidence suggested that, during the first postnatal day, neonates who developed NEC had a significantly higher peak systolic velocity (mean difference of 2.65 cm/s (95% confidence interval [CI] 1.23, 4.06, overall effect Z=3.66, P<0.001)), higher PI (mean difference of 1.52 (95% CI 0.00, 3.04, Z=1.96, P=0.05)) and higher resistive index (mean difference of 1.09 (95% CI 0.59, 1.60, Z=4.24, P<0.001)), compared to neonates who did not develop NEC. However, our findings do not support a strong association between the Doppler ultrasound indices and development of NEC at the time of disease onset. This meta-analysis suggests that first postnatal day SMA Doppler parameters, namely peak systolic velocity, PI and resistive index, are higher in neonates who develop NEC. On the other hand, the aforementioned indices are of uncertain significance once the diagnosis of NEC has been established., (© 2023. The Author(s).)

The ongoing Coronavirus disease 19 (Covid-19) pandemic and associated mortality in children led to an effort to address risk factors and develop protective measures. Observational studies in adults showed that vitamin D deficiency is associated with Covid-19 severity. The aim of this review was to summarise data regarding the role of serum vitamin 25(OH)D concentration in the severity of Covid-19 and the associated multisystem inflammatory syndrome in children (MIS-C). Many studies noted lower concentrations of vitamin 25(OH)D in children with Covid-19 compared with healthy controls; however, studies that assessed vitamin 25(OH)D suboptimal concentrations as a risk factor for Covid-19 severity were scarce. There was no high-quality evidence that vitamin 25(OH)D concentrations are associated with Covid-19 severity. Similarly, for MIS-C, a few studies with a small number of patients found that vitamin D deficiency was associated with more severe MIS-C. Vitamin D has many immunomodulatory actions and is consumed in the immunomodulatory cells, especially in infections such as the Covid-19 which is associated with increased inflammation and cytokine storm. Therefore, decreased concentrations of plasma vitamin 25(OH)D have been proposed to be the result of vitamin use by immunomodulatory cells in severe Covid-19, rather than a predisposing factor. In conclusion, the available data cannot prove that vitamin D deficiency is a risk factor for severe Covid-19 disease. More studies, of prospective design, are needed to investigate the role of this marker independently of other risk factors.

Evidence supports that growth trajectory during infancy has a major impact on body composition. We aimed to examine body composition in children born small for gestational age (SGA) or appropriate for gestational age (AGA) adjusted for postnatal growth velocity. We enrolled 365 children, 75 SGA and 290 AGA, aged 7 to 10 years, examining anthropometrics, skinfold thickness, and body composition using bioelectrical impedance analysis. Growth velocity was defined as rapid or slow (weight gain > or <0.67 z-scores, respectively). Gestational age, sex, delivery mode, gestational diabetes, hypertension, nutrition, exercise, parental body mass index (BMI), and socioeconomic status were considered. At a mean of 9 years of age, SGA compared with AGA-born children, had significantly lower lean mass. BMI was negatively associated with SGA status (beta = 0.80, P = .046), after adjusting for birth weight, delivery mode, and breastfeeding. The lean mass index was negatively associated with SGA status (beta = 0.39, P = .018), after adjusting for the same factors. SGA-born participants with slow growth velocity had significantly lower lean mass in comparison to AGA-born counterparts. SGA-born children with rapid compared with those with slow growth velocity had significantly higher absolute fat mass. BMI was negatively associated with a slow postnatal growth pattern (beta = 0.59, P = .023), and the lean mass index was negatively associated with a slow postnatal growth pattern (beta = 0.78, P = .006), after adjusting for the same factors. In conclusion, SGA-born children presented a lower lean mass in comparison to AGA-born counterparts, whereas BMI and lean mass index were negatively associated with slow postnatal growth velocity., Competing Interests: Author Declarations None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: this post hoc analysis aimed to evaluate the efficacy of fremanezumab in difficult-to-treat chronic migraine (CM) patients with and without psychiatric comorbidities (PCs), mainly anxiety and/or depression., Methods: We assessed data from CM patients with and without PCs who failed at least 3 preventives and eventually received at least 3 consecutive monthly doses of fremanezumab 225 mg. Outcomes included the crude response (≥50% reduction in monthly headache days (MHDs)) rates to fremanezumab from the baseline to the last clinical follow-up. The changes in MHDs; MHDs of moderate/greater severity; monthly days with intake of abortive medication; and the proportion of patients' changing status from with PCs to decreased/without PCs were also compared. Disability and quality of life (QOL) outcomes were also assessed., Results: Of 107 patients enrolled, 65 (60.7%) had baseline PCs. The percentage of patients with ( n = 38/65; 58.5%) and without ( n = 28/42; 66.6%) PCs that achieved a ≥50% reduction in MHDs with fremanezumab was comparable ( p = 0.41), whereas MHDs were significantly reduced (difference vs. baseline) in both patients with PCs (mean -8.9 (standard error: 6.8); p < 0.001) and without PCs (-9.8 (7.5); p < 0.001). Both groups experienced significant improvements in all other efficacy, disability, and QOL outcomes at comparable rates, including in MHD reduction. A significant proportion of fremanezumab-treated patients with baseline PCs de-escalated in corresponding severities or even reverted to no PCs (28/65; 43.1%) post-fremanezumab., Conclusions: fremanezumab appears to be effective as a preventive treatment in difficult-to-treat CM patients with and without PCs while also being beneficial in reducing the severity of comorbid anxiety and/or depression.

Data regarding the nutritional management of preterm small for gestational age (SGA) infants are scarce. In the recent report of ESPGHAN, the recommended energy for very preterm infants during hospitalization has been increased, yet this may not fit the needs of all preterm infants. It is important to distinguish fetal growth-restricted (FGR) infants from constitutional SGA infants, as well as preterm SGA from preterm AGA infants, since they may have different nutritional needs. Preterm FGR infants, and specifically infants < 29 weeks' gestation, accumulate nutrient deficits due to intrauterine malnutrition, prematurity, morbidities, delayed initiation of feeding, and feeding intolerance. Therefore, these infants may need more aggressive nutrition for optimal catch-up growth and neurologic development. However, a balance should be kept between optimal and excessive catch-up growth, since the combination of intrauterine malnutrition and excessive postnatal growth has been linked with later adverse metabolic consequences. Furthermore, multiple gestation is often complicated by FGR and prematurity. There is controversy in the definition of FGR in multiple gestations, and it should be noted that FGR in multiple gestation usually differs etiologically from FGR in singletons. The aim of this review is to summarize existing knowledge regarding the nutritional needs of preterm FGR and FGR infants of multiple gestation.

Aim: To evaluate the predictive value of perinatal factors and neurodevelopmental evaluation in the emotional and behavioural outcomes in preterm-born children at 7-9 years of age., Methods: We evaluated the Strengths and Difficulties Questionnaire (SDQ) extended score at 8.2 ± 0.2 years, among 70 preterm-born children (32 early and 38 moderately preterms) with a previous Bayley-III neurodevelopmental evaluation., Results: Early compared to moderately preterms had a higher total SDQ (12 compared to 8, p = 0.031), and emotional symptoms score (4 compared to 3, p = 0.022); no significant differences were recorded in abnormal/borderline-scored children between the two groups. The total SDQ and emotional symptoms scores were significantly correlated with gestational age, birth weight, perinatal factors and the cognitive and motor Bayley-III scores. Early prematurity was associated with the total SDQ score (beta 2.09, 95% CI 1.32, 3.87), and the score of emotional symptoms (beta 1.70, 95% CI 1.38, 2.19), after adjusting for sex, neonatal sepsis and the existence of an older sibling., Conclusion: Prematurity, birth weight, perinatal factors and the cognitive and motor Bayley-III scores were significantly associated with the total SDQ and the emotional symptoms score, in preterm-born children., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: A term neonate presented with persistent severe thrombocytopenia, elevated liver enzymes, conjugated hyperbilirubinemia, hepatosplenomegaly, and mild hypotonia., Observations: A thorough workup for infections, congenital thrombocytopenias, and neonatal malignancies was negative. Because of increased anti-SARS-CoV-2 IgG antibodies after maternal COVID-19, multisystem inflammatory syndrome of neonates was considered and intravenous immunoglobulin was administered. The clinical condition of the neonate deteriorated and due to laboratory evidence of hyperinflammation, hemophagocytic lymphohistiocytosis was suspected, and treatment with etoposide and dexamethasone was initiated with temporary stabilization. Gaucher disease type 2 was eventually diagnosed., Conclusion: Gaucher disease can rarely present in neonates as hemophagocytic lymphohistiocytosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To prospectively assess the efficacy and safety of fremanezumab for migraine prophylaxis in patients with failure of at least three previous preventive treatments. Changes in disability as quality-of-life outcomes after fremanezumab treatment were also examined., Methods: Two hundred and four patients with either high-frequency EM (HFEM) or chronic migraine (CM), who attained at least three consecutive monthly sessions with fremanezumab 225 mg and otherwise met the inclusion criteria, were included in the study. The crude response (at least 50% reduction in monthly headache days [MHD]) rates to fremanezumab were assessed. Scores in the following efficacy outcomes were then compared from baseline to the last efficacy evaluation follow-up: (i) MHD, (ii) monthly days with moderate/severe peak headache intensity, and (iii) monthly days with intake of abortive medication. The disability was evaluated with the Migraine Disability Assessment; the quality of life (QOL) status was assessed with the Headache Impact-6 Test, and the EQ-5D questionnaire., Results: In the majority of HFEM cases (n = 81/97; 83.5%) and CM patients (n = 67/107; 62.6%), fremanezumab proved effective in reducing the MHDs by at least 50% and was associated with clinically meaningful improvement in all other efficacy variables. The migraine-related disability experienced by our patients decreased and their QOL increased. We recorded just 36 cases reporting mild adverse events, including pain, rash or pruritus (n = 26), flu-like symptoms (n = 8), and hair loss (n = 2)., Conclusion: With our prospective results, we provide further real-world data to support the favorable benefit/risk profile of fremanezumab in the prophylaxis of both HFEM and CM., (© 2023 European Academy of Neurology.)

Objective: To define, in a real-world population of patients with high-frequency episodic (HFEM) or chronic migraine (CM), the predictive role of socio-demographic or phenotypic profiling of responders to fremanezumab., Patients and Methods: Two-hundred and four adult fremanezumab-treated patients with either HFEM or CM, who failed to at least three preventive treatments, provided data at baseline on several individual socio-demographic and phenotypic variables. These variables were analyzed for their ability to independently predict the response (50-74% response rates) or super-response (≥ 75% response rates) to fremanezumab. Patients were followed from 3-18 months of fremanezumab exposure., Results: The main finding to emerge from univariate analyses was that three baseline socio-demographic/clinical variables, i.e., age group 41-70 years ( p = 0.02); female gender ( p = 0.03); patients with HFEM ( p = 0.001), and three clinical phenotypic variables, i.e., strict unilateral pain ( p = 0.05); pain in the ophthalmic trigeminal branch ( p = 0.04); and the "imploding" quality of pain ( p = 0.05), were significantly related to fremanezumab response. However, in multivariate analysis, only HFEM ( p = 0.02), the presence of strict unilateral ( p = 0.03), and pain location in the ophthalmic trigeminal branch ( p = 0.036) were independently associated with good fremanezumab response. Allodynia ( p = 0.04) was the only clinical predictive variable of super-responsiveness to fremanezumab., Conclusions: A precise phenotypic profiling with identification of pain characteristics consistent with peripheral and/or central sensitization might reliably predict the responsiveness to fremanezumab in migraine prophylaxis.

The consistently high prevalence of cardiovascular disease (CVD) has urged the need for punctual and effective prevention. Extended research on this specific area has demonstrated the influence of fetal and neonatal periods on the risk of developing CVD in adulthood. Thus, the role of traditional and novel biological markers to the effective screening of CVD among the neonatal population is widely investigated. The objective of the present narrative review is to examine those neonatal biomarkers that may play a role in the development of CVD, to exhibit scientific data that appertain to their association with various perinatal conditions leading to CVD predisposition, and their potential role on prediction and prevention strategies. Multiple biomarkers, traditional and novel, have been mined across the studied literature. Adiposity, insulin resistance, altered lipid profile, inflammation, and endothelial dysfunction seem among the headliners of CVD. Even though various novel molecules have been studied, their clinical utility remains controversial. Therefore, it is quite important for the scientific community to find elements with strong predictive value and practical clinical use.