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Deep learning (DL)-based Human Activity Recognition (HAR) using wearable inertial measurement unit (IMU) sensors can revolutionize continuous health monitoring and early disease prediction. However, most DL HAR models are untested in their robustness to real-world variability, as they are trained on limited lab-controlled data. In this study, we isolated and analyzed the effects of the subject, device, position, and orientation variabilities on DL HAR models using the HARVAR and REALDISP datasets. The Maximum Mean Discrepancy (MMD) was used to quantify shifts in the data distribution caused by these variabilities, and the relationship between the distribution shifts and model performance was drawn. Our HARVAR results show that different types of variability significantly degraded the DL model performance, with an inverse relationship between the data distribution shifts and performance. The compounding effect of multiple variabilities studied using REALDISP further underscores the challenges of generalizing DL HAR models to real-world conditions. Analyzing these impacts highlights the need for more robust models that generalize effectively to real-world settings. The MMD proved valuable for explaining the performance drops, emphasizing its utility in evaluating distribution shifts in HAR data.

Background: The issue of retreatment with surfactant of infants with respiratory distress syndrome (RDS) has been poorly investigated. Our aim was to identify possible clinical predictors of the need for multiple doses of surfactant in a large cohort of very preterm infants., Methods: Data were analyzed from three previous studies on infants born between 25 + 0 and 31 + 6 weeks of gestation with RDS who were treated with surfactant., Results: We studied 448 infants. Among them 306 (68%) were treated with a single dose of surfactant and 142 (32%) were treated with multiple doses. Multivariable mixed effects logistic regression analysis showed that the odd of requiring multiple doses of surfactant was significantly lower in patients with higher gestational age (27-28 vs. 25-26 wks: OR 0.46, 95% C.l. 0.26-0.79; ≥29 vs. 25-26 wks: OR 0.34, 95% C.l. 0.13-0.85; overall P = 0.013), while it increased in infants born to mothers with hypertensive disorders of pregnancy (OR 2.53, 95% C.l. 1.49-4.31; P < 0.001) and with hemodynamically significant PDA (OR 2.74, 95% C.l. 1.66-4.53, P < 0.001)., Conclusions: Gestational age, hypertension in pregnancy, and hemodynamically significant PDA can predict the need for multiple doses of surfactant. Further investigation is needed to evaluate if these sub-groups of preterm infants represent specific phenotypes of RDS who deserve a peculiar surfactant treatment., Competing Interests: Declarations. Ethics approval and consent to participate: All studies used for pooled analyses were approved by pediatric ethics committees of Tuscany (ID 29/2011, ID 234/2019, and ID 58/2019, respectively) and carried out in accordance with the 1964 Declaration of Helsinki. Infants were enrolled after informed parental consent. Only data of infants who were treated with surfactant were analyzed. Local ethics committees approved the study. Parental consent was not required because this is a retrospective study and data were anonymized. Consent for publication: Not applicable. Competing interests: Prof. Carlo Dani received honoraria from Chiesi Farmaceutici SpA and Vyaire Medical Inc. for scientific consultancies. Other authors declare that there are no conflicts of interests. Prof. Carlo Dani and Dr. Raffaele Falsaperla are members of the Editorial Board of the Italian Journal of Pediatrics., (© 2024. The Author(s).)

Background: Wearable sensors are rapidly evolving, particularly in health care, due to their ability to facilitate continuous or on-demand physiological monitoring., Objective: This study aimed to design and validate a wearable sensor prototype incorporating photoplethysmography (PPG) and long-range wide area network technology for heart rate (HR) measurement during a functional test., Methods: We conducted a transversal exploratory study involving 20 healthy participants aged between 20 and 30 years without contraindications for physical exercise. Initially, our laboratory developed a pulse wearable sensor prototype for HR monitoring. Following this, the participants were instructed to perform the Incremental Shuttle Walk Test while wearing the Polar H10 HR chest strap sensor (the reference for HR measurement) and the wearable sensor. This test allowed for real-time comparison of HR responses between the 2 devices. Agreement between these measurements was determined using the intraclass correlation coefficient (ICC 3.1 ) and Lin concordance correlation coefficient. The mean absolute percentage error was calculated to evaluate reliability or validity. Cohen d was used to calculate the agreement's effect size., Results: The mean differences between the Polar H10 and the wearable sensor during the test were -2.6 (95% CI -3.5 to -1.8) for rest HR, -4.1 (95% CI -5.3 to -3) for maximum HR, -2.4 (95% CI -3.5 to -1.4) for mean test HR, and -2.5 (95% CI -3.6 to -1.5) for mean recovery HR. The mean absolute percentage errors were -3% for rest HR, -2.2% for maximum HR, -1.8% for mean test HR, and -1.6% for recovery HR. Excellent agreement was observed between the Polar H10 and the wearable sensor for rest HR (ICC 3.1 =0.96), mean test HR (ICC 3.1 =0.92), and mean recovery HR (ICC 3.1 =0.96). The agreement for maximum HR (ICC 3.1 =0.78) was considered good. By the Lin concordance correlation coefficient, the agreement was found to be substantial for rest HR (r c =0.96) and recovery HR (r c =0.96), moderate for mean test HR (r c =0.92), and poor for maximum HR (r c =0.78). The power of agreement between the Polar H10 and the wearable sensor prototype was large for baseline HR (Cohen d=0.97), maximum HR (Cohen d=1.18), and mean recovery HR (Cohen d=0.8) and medium for mean test HR (Cohen d= 0.76)., Conclusions: The pulse-wearable sensor prototype tested in this study proves to be a valid tool for monitoring HR at rest, during functional tests, and during recovery compared with the Polar H10 reference device used in the laboratory setting., (©Fernanda Laís Loro, Riane Martins, Janaína Barcellos Ferreira, Cintia Laura Pereira de Araujo, Lucio Rene Prade, Cristiano Bonato Both, Jéferson Campos Nobre Nobre, Mariane Borba Monteiro, Pedro Dal Lago. Originally published in JMIR Biomedical Engineering (http://biomsedeng.jmir.org), 11.12.2024.)

Background and Aims: Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting., Methods: The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin-2, lactoferrin, and resistin (non-neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA., Results: Over up to 2 years of follow-up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin-2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75-0.85); all other correlations were of small magnitude., Conclusion: Our real-world data do not support using serum neutrophil elastase, lipocalin-2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab -treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p -AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

Aim: This study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration., Methods: In this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series., Results: Seventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m 2 , FEV 1, 0.79 (0.67-1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels., Conclusions: Acute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect., Competing Interests: Declaration of competing interest On Behalf of the authors, I declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions., Methods: A web-based survey was distributed to neonatal units worldwide., Results: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always., Conclusions: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries.

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

Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis. Photobiomodulation (PBM) has been utilized in experimental models of cardiac hypoxia to enhance mitochondrial response and ameliorate biochemical changes in injured tissue. However, the effects of PBM on cultured cardiomyocytes subjected to hypoxia/reoxygenation are not yet well established., Method: H9C2 cardiomyocytes were exposed to hypoxia with concentrations of 300 μM CoCl 2 for 24 h, followed by 16 h of reoxygenation through incubation in a normoxic medium. Treatment was conducted using GaAIAs Laser (850 nm) after hypoxia at an intensity of 1 J/cm 2 . Cells were divided into three groups: Group CT (cells maintained under normoxic conditions), Group HR (cells maintained in hypoxia and reoxygenation conditions without treatment), Group HR + PBM (cells maintained in hypoxia and reoxygenation conditions that underwent PBM treatment). Cell viability was analyzed using MTT, and protein expression was assessed by western blot. One-way ANOVA with the Tukey post hoc test was used for data analysis. Differences were significant when p < 0.05., Results: PBM at an intensity of 1 J/cm 2 mitigated the alterations in cell survival caused by hypoxia/reoxygenation. Additionally, it significantly increased the expression of proteins Nrf2, HSP70, mTOR, LC3II, LC3II/I, and Caspase-9, while reducing the expression of PGC-1α, SOD2, xanthine oxidase, Beclin-1, LC3I, and Bax., Conclusion: PBM at intensities of 1 J/cm 2 reverses the changes related to oxidative stress, mitochondrial biogenesis, autophagy, and apoptosis caused by hypoxia and reoxygenation in a culture of cardiomyocytes., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest is relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Congenital pulmonary airway malformations (CPAMs) represent a well-known cluster of rare lung malformations affecting 1 in 2500 live births. The natural history of many CPAMs is to increase their size in the second trimester, reach a plateau, and, in about 50% of cases, regress and to become barely detectable during the third trimester. Little is known about cases of affected neonates born prematurely: only six cases are described in the literature, recording different conduct and outcomes. Herein, we report the case of a very low birth weight infant born at GW 28 without antenatal findings and presenting at birth with severe respiratory distress, requiring ventilation. Chest X-rays and a CT scan showed the presence of a solid mass in the left lung. An initial conservative approach was adopted as the baby gained respiratory stability within the first days of life. Routine ultrasound (US) showed a progressive reduction of the lesion, mimicking the process of involution that CPAM can exhibit during late gestation. The rarity of the condition does not allow the formulation of any suggestions regarding one type of management over the other. An initial conservative approach seems to be appropriate with regards to the outcome and possible intra- and post-operative complications.

Background and Aims: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment., Methods: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model., Results: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression., Conclusion: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration., Methods: In this study, 382 infants born at 24 +0 -27 +6  weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24 +0 to 25 +6  weeks or 26 +0 to 27 +6  weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR)., Discussion: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24 +0 -27 +6  weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life., Trial Registration: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023., (© 2024. The Author(s).)

Background: Patients with idiopathic pulmonary fibrosis (IPF) often present with dyspnea, fatigue, and desaturation. These symptoms can be highly limiting, as they lead to a decrease in performing activities of daily living (ADL). Therefore, it is essential to evaluate the degree of functional limitation of these individuals., Objective: The present study aimed to evaluate the validity and reliability of the Glittre-ADL test (TGlittre) and its association with self-reported limitation in ADL and health-related quality of life (HRQoL) in patients with IPF., Methods: Twenty-seven individuals with IPF (60.5 ± 10.6 years), with forced vital capacity 2.26 ± 1.03 L (51.09 ± 20.62% of predicted) were assessed for the time spent in TGlittre, 6-minute walking distance (6MWD), limitation in ADL and HRQoL., Results: TGlittre was reliable (intraclass correlation coefficient 3,1  = 0.96; P < .001); however, a learning effect of 10.6% was observed between the first and second execution of TGlittre. The time spent in TGlittre correlated with 6MWD, limitation in ADL, and disease-specific HRQoL (P < .05)., Conclusion: TGlittre is valid and reliable for assessing functional capacity in patients with IPF. Still, it presents a learning effect and should be performed twice when assessing functional capacity in clinical practice.

Background: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines., Aims: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab., Methods: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure., Results: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021)., Conclusion: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration., Competing Interests: Conflict of interest PS served as speaker for Janssen and received Congress support from Janssen, Abbvie, Dr. Falk, Norgine and Pfizer. IR reports personal fees and/or non-financial support from Faes Pharma, Ferring, Pharmakern, Janssen and Takeda, outside the submitted work. She also reports research grants from Abbvie and Ferring, outside the submitted work. HTS served as speaker for Janssen and received Congress support from Abbvie, Ferring, Janssen, Pfizer, Takeda, Tillots, Dr. Falk and Biogen. FM served as a speaker and received honoraria from Abbvie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratórios Vitória, Lilly, Pfizer, Merck Sharp & Dohme, Sandoz, Takeda, UCB and Vifor. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV)., Objectives: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP., Materials and Methods: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25 +0 -31 +6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO 2 /FiO 2 ratio after LISA, and adverse effect rate., Results: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO 2 /FiO 2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms., Conclusions: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA., (© 2024 Wiley Periodicals LLC.)

Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy., Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves., Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic., Conclusion: The risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Tofacitinib is an oral small molecule JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). Its efficacy and safety have been demonstrated in phase III clinical trials and supported by real-life data. We report the case of an 18-year-old woman with a 1-year diagnosis of left-sided UC, with multiple admissions due to disease exacerbation or infections, refractory to infliximab (with azathioprine) and currently under treatment with vedolizumab and tacrolimus. She was admitted due to a severe disease exacerbation and, because of a previous history of neuropsychiatric side effects to corticotherapy, tofacitinib was initiated. In the following 6 days, there was no clinical improvement of UC, and serial blood work-up revealed moderate grade persistent peripheral eosinophilia (3000 cells/mm3) and acute kidney injury grade 1 KDIGO. Tofacitinib temporary suspension was decided, with a rapid normalization of renal function/eosinophil levels. Tofacitinib was restarted 2 days after its suspension. However, she developed moderate eosinophilia (2000 cells/mm3) again, which was considered an adverse effect (AE) to tofacitinib, leading to its suspension with eosinophilia resolution. Given the severity of the disease, after a multidisciplinary discussion, it was decided to start high-dose corticotherapy and ustekinumab with maintenance therapy every 4 weeks, and to add tacrolimus. Clinical and biochemical remission were achieved, and the patient was discharged. Three-month follow-up after tofacitinib suspension showed no recrudescence of eosinophilia. Tofacitinib represents a significant advance in the management of UC patients. The drug has a good safety profile with few related AE. This case aims to warn about an adverse reaction to tofacitinib not reported so far, including in a multicenter real-life setting recently published by Hernández et al where eosinophilia is also not described, thus emphasizing the rarity of this AE. To our knowledge this is the first case of tofacitinib-induced eosinophilia in the context of UC. .

Background: Cardiovascular diseases are a leading cause of mortality worldwide. A significant contributing factor to this mortality is the lack of engagement in preventive activities. Consequently, strategies for enhancing adherence to and duration of physical activity (PA) have become pivotal. This project aims to create and validate innovative, disruptive, and secure technologies that ensure appropriate exercise intensity, bolster adherence to PA, and monitor health biomarker responses pre-, during, and post-physical activity., Methods: This exploratory study, followed by a noninferiority, investigator-blinded randomized clinical trial, will be divided into three phases: (1) development and validation of a sensor for real-time biofeedback during a functional assessment test; (2) integration of biofeedback and gamification into an app for the structured prescription of physical training within a controlled setting; and (3) implementation of biofeedback and gamification into an app for the prescription and monitoring of physical training in an uncontrolled setting. Phase 1 entails a validation test of a biosensor-monitoring heart rate (HR) and steps-during a modified shuttle walk test. In phase 2, the biosensor interfaces with a gamified smartphone application. The training regimen spans 6 weeks, 5 days weekly, with each session lasting 60 min: a five-min warm-up involving stationary gait, followed by 50 min of training at the target HR on the step and concluding with a five-min cool-down at a stationary pace. After 6 weeks of training, a new functional capacity test is conducted. Phase 3 involves an investigator-blinded, randomized clinical trial to demonstrate noninferiority. Participants are randomly assigned to either the intervention group (IG) or the control group (CG). IG participants practice exercise using the gamified application in an uncontrolled environment according to the prescribed method outlined in phase 2. CG participants receive PA practice guidelines exclusively., Discussion: Anticipated outcomes include improved exercise adherence through the gamified application, better maintenance of prescribed exercise intensity, and enhanced health biomarkers. The results of this study will inform health-related decision-making., Trial Registration: The study protocol received approval from the Ethics Committee of Universidade Federal de Ciências da Saúde de Porto Alegre (54,492,221.80000.5345) and has been registered with the Brazilian Registry of Clinical Trials (ReBEC, RBR-359p69v)., (© 2023. The Author(s).)

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl's pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion-1 mcg/kg/h-during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species., (© 2023. The Author(s).)

Background: Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD., Objective: We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression., Methods: Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices., Results: The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 μg/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 μg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes., Conclusion: The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

New Findings: What is the central question of the study? Does β-alanine with l-histidine supplementation associated with endurance and strength training improve echocardiographic parameters, functional capacity, and maximum strength in rats with chronic heart failure? What is the main finding and its importance? β-Alanine with l-histidine supplementation associated with endurance and strength training increased functional capacity and maximum strength through increasing exercise capacity peripherally but did not affect echocardiographic parameters in rats with chronic heart failure. Combined training (CT) has been associated with positive responses in the clinical status of patients with chronic heart failure (CHF). Other non-pharmacological tools, such as amino acid supplementation, may further enhance its adaptation. However, the effects of β-alanine and l-histidine supplementation in CHF remain unclear. In the present study, the aim was to test whether supplementing carnosine precursors with CT could give improved responses in the functional capacity and echocardiographic variables of rats with CHF. Twenty-four Wistar rats, were submitted to myocardial infarction and allocated to three groups: animals with CHF kept in sedentary conditions (SED, n = 8), animals with CHF submitted to CT in strength and aerobic exercise supplemented with placebo (CT-P, n = 8) and animals with CHF submitted to CT in strength and aerobic exercise supplemented with β-alanine and l-histidine (CT-S, n = 8). The trained animals were submitted to a strength protocol three times per week with intensity of 65-75% of one repetition maximum test. Aerobic training was conducted two times per week (50 min, 15 m min -1 ). The supplemented group received β-alanine and l-histidine orally (each 250 mg kg -1  day -1 ). No changes in echocardiographic and morphological parameters were found among the groups (P > 0.05). Functional capacity, Δ V ̇ O 2 max and maximum strength were higher in CT-P than in SED and even higher in CT-S than in CT-P (P < 0.01). The CT was able to improve functional capacity, but the supplementation was shown to enhance these parameters even further in the CHF rats. We conclude that the increase in functional capacity and strength gained through CT and supplementation were associated with the improvement in peripheral parameters with no changes in cardiac variables., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test., Materials and Methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates., Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test ( P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities ( P < 0.05; effect size = 0.7765)., Conclusion: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

Background: Preterm birth is a risk factor for a child's neurological development. Preterm children have unusual neurodevelopmental profiles with executive, visual-motor functions, fine and gross motor skills, language and behavior that affect learning. In this study, we analyzed the neurodevelopmental outcomes of a cohort of very low birth weight infants admitted to the Treviso Neonatal Intensive Care Unit (NICU) between 2014 and 2016 and followed up to preschool childhood., Method: This is a prospective cohort study. Infants were followed at birth and after NICU discharge at two- and four-year follow-ups. The two-year assessment was conducted with Bayley III, and at four years with the Wechsler Preschool and Primary Scale of Intelligence - III scales and Movement Assessment Battery for Children - 2., Results: The cohort consisted of 207 subjects with a mean gestational age of 28.9 weeks, and a mean birth weight of 1097.2 g. At two years of age, children without disabilities were 90 (59.6%), those with minor disabilities 47 (31.1%), and those with major disabilities 14 (9.3%); at four years, 58.4% of children without previous disabilities, presented problems with verbal tests and manual dexterity: aiming, grasping and balance at movement assessment. There was significant alteration in processing speed (p < 0.001). Furthermore, there was a strong correlation between processing speed and manual dexterity (p < 0.001) and between processing speed and aiming and grasping (p = 0.0059)., Conclusions: We found that more than half the children free of disability at two years, at four years had deficit often involving the oculo-motor coordination and processing speed. These motor profile alterations limit the expression of cognitive abilities and the achievement of expected school performance, thus resulting in behavioral disorders, typical of preterm children. Early professional follow-up could improve the expected educational outcomes., (© 2023. The Author(s).)

Introduction: Therapeutic hypothermia is the standard care for asphyxiated newborns. Discomfort and pain during treatment are common and may affect therapeutic efficacy of hypothermia. Opioid analgosedation is commonly used in the clinical setting, but its effects in the cooled newborns is poorly investigated., Objective: The aim of this study was to assess the safety of fentanyl analgosedation during therapeutic hypothermia, by evaluating severe adverse effects and possible correlation with the neurodevelopmental outcome., Methods: We analyzed asphyxiated newborns treated with hypothermia receiving fentanyl intravenous infusion (years 2013-2018). Severe neurodevelopmental outcome was defined as cerebral palsy or Griffith's developmental quotient <70 or major sensorineural deficit. Severe brain lesions were defined as cortical or/and basal ganglia extensive involvement., Results: Fentanyl cumulative dose was variable (61.7 ± 18.5 µg/kg; range 34.3-120.3 µg/kg) among 45 enrolled patients. Respiratory depression was recorded in 13.3% cases of 30 spontaneously breathing patients. Severe brain lesions and severe neurodevelopmental disability were found in 24.4 and 11.1% of all included cases, respectively. Higher cumulative fentanyl dose was not associated with poor outcome., Conclusions: Fentanyl treatment during therapeutic hypothermia does not negatively affect the neurodevelopmental outcome, thus on the contrary, it may contribute to ameliorate neuroprotection in the asphyxiated cooled newborns.

Background: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal., Methods: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY., Results: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010., Conclusions: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Sepsis is one of the most urgent health care issues worldwide. Guidelines for early identification and treatment are essential to decrease sepsis-related mortality. Our aim was to collect data on the epidemiology of pediatric septic shock (PSS) from the emergency department (PED) and to assess adherence to recommendations for its management in the first hour., Methods: A multicenter, prospective, cross-sectional study was conducted evaluating children with PSS seen at the PED of 10 tertiary-care centers in Latin America. Adherence to guidelines was evaluated., Results: We included 219 patients (median age, 3.7 years); 43% had comorbidities, 31% risk factors for developing sepsis, 74% clinical signs of "cold shock," and 13% of "warm shock," 22% had hypotension on admission. Consciousness was impaired in 55%. A peripheral line was used as initial access in 78% (median placement time, 10 minutes). Fluid and antibiotics infusion was achieved within a median time of 30 minutes (interquartile range [IQR], 20-60 minutes) and 40 minutes (IQR, 20-60 minutes), respectively; 40% responded inadequately to fluids requiring vasoactive drugs (median time at initiation, 60 minutes; IQR, 30-135 minutes). Delay to vasoactive drug infusion was significantly longer when a central line was placed compared to a peripheral line (median time, 133 minutes [59-278 minutes] vs 42 minutes [30-70 minutes], respectively [ P < 0.001]). Adherence to all treatment goals was achieved in 13%. Mortality was 10%. An association between mortality and hypotension on admission was found (26.1% with hypotension vs 4.9% without; P < 0.001)., Conclusions: We found poor adherence to the international recommendations for the treatment of PSS in the first hour at the PED in third-level hospitals in Latin America., Competing Interests: Disclosure: The authors declare no conflict of interest, (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers., Methods: The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 μg/g, >250 μg/g, or >350 μg/g) or serum CRP (>3 μg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation., Results: Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98-515] μg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80-6.00] μg/mL; P = .895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 μg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557-5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 μg/mL, FC >150 μg/g, FC >350 μg/g, double biomarkers (FC >250 μg/g and/or CRP >3 μg/mL), or more visits did not improve predictive ability., Conclusions: Persistent inflammation, defined simply and readily by FC >250 μg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Inflammatory bowel diseases' (IBD) increasing incidence and prevalence place a heavy health and economic burden on society., Objectives: This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care., Methods: The burden of disease was expressed using disability-adjusted life years (DALY). Costs were estimated considering the societal perspective, using a prevalence-based model and prices established by law. An expert panel composed of 5 expert Portuguese gastroenterologists and a patient-reported study were conducted to support the cost analysis and fill in information gaps., Results: In Portugal, with a prevalence of 24,069 IBD patients and an incidence of 15/100,000, the burden of disease was estimated at 6,067 DALYs: 507 resulting from premature deaths and 5,560 from disability. Total cost was estimated at EUR 146 million per year, with direct costs representing 59%. Average yearly cost per IBD patient is EUR 6,075, where 60% is related to Crohn's disease and 40% to ulcerative colitis (UC)., Conclusion: This study estimates the annual health burden and cost of IBD in Portugal, thus generating information with the intent to raise awareness of the need to advance health policies as well as better clinical and economic decisions in this pathology., Competing Interests: Fernando Magro, Francisco Portela, Paula Lago, Cristina Chagas, and Luis Correia received honoraria from Janssen for participation in expert panel. Bernardo Rodrigues is an employee of Janssen Portugal. Francisco Moreira, Fábio Pereira, and Hugo Pedrosa are employees of IQVIA Portugal and were contracted by Janssen Portugal for the development of this article., (Copyright © 2022 by Sociedade Portuguesa de Gastrenterologia. Published by S. Karger AG, Basel.)

Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: This cohort study included patients with CD and UC followed in 6 secondary and tertiary care centers in mainland Portugal. Patients were divided into a derivation (80%) cohort and a validation (20%) cohort. The primary outcome was progressive disease. Logistic regression analysis, receiver operating characteristic curves, and the areas under the curve (AUC) were performed. Odds ratios with 95% confidence intervals (CIs) were estimated., Results: The derivation cohorts included 1245 patients with CD (68% with progressive disease) and 1210 patients with UC (37% with progressive disease), whereas the validation cohorts included 302 patients with CD and 271 patients with UC, respectively, with similar outcome proportions. In our final model, age at diagnosis older than 60 years was significantly associated with a lower risk of developing progressive disease (odds ratio 0.390, 95% CI 0.164-0.923, P = 0.032), with a high discriminative power (AUC 0.724, 95% CI 0.693-754) in patients with CD. However, according to this model, no significant associations were found between age at diagnosis and the risk of developing progressive disease in patients with UC. No differences were observed in the AUC values between the validation and the derivation cohorts., Discussion: Patients with elderly-onset CD, but not patients with UC, were associated with a less progressive course of the disease., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: This systematic review and meta-analysis aims to assess composite and aggregate outcomes of observational studies in Crohn's disease and to evaluate whether the number and type of variables included affect the frequency of the outcome., Methods: MEDLINE [via PubMed], Scopus and Web of Science were searched to identify observational studies that enrolled patients with Crohn's disease and evaluated a composite or aggregate outcome. The proportion of patients achieving the outcome was determined and a random-effects meta-analysis was performed to evaluate how the frequency of each outcome varies according to the reporting of predefined variables., Results: From 10,257 identified records, 46 were included in the qualitative analysis and 38 in the meta-analysis. The frequency for composite and aggregate outcomes was 0.445 [95% confidence interval (CI): 0.389-0.501] and 0.140 (95% CI: 0.000-0.211), respectively. When comparing composite outcomes by number of included variables, the frequency was 0.271 (95% CI: 0.000-0.405) and 0.698 (95% CI: 0.651-0.746), for one and six variables, respectively. The frequency of the composite outcome varied according to the identity of the variables being reported. Specific pairs of predefined variables had a significant effect in the frequency of composite outcomes., Conclusion: Composite outcomes with increasing number of predefined variables show an increase in frequency. Outcomes including variables such as 'Surgery' and 'Steroids' had higher frequencies when compared with the ones that did not include these variables. These results show that the frequency of composite outcomes is dependent on the number and type of variables being reported., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FM received a fee for presenting from AbbVie, Ferring, Falk, Hospira, PharmaKern, MSD, Schering, Laboratórios Vitoria, Vifor Pharma and OM Pharma. AD reports fees for participation in clinical trials, review activities, such as data monitoring boards, statistical analysis, end point committees from Falk, Abbvie, Janssen, Gilead and Pfizer; consultancy fees from Abbvie, MSD, Ferring, Roche/Genentech, Takeda, Vifor, Pharmacosmos, Boehringer-Ingelheim, Falk, Janssen, Pfizer, Sandoz/Hexal, BMS/ Celgene, Tillotts, Galapagos, Amgen and Fresenius Kabi; payment from lectures including service on speakers bureaus from Falk Foundation, Ferring, MSD, Abbvie, Vifor, Janssen, Pfizer, Tillotts, Takeda, Gilead/Galapagos; payment for article preparation from Falk Foundation, Thieme, Takeda and UniMed Verlag. SD has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor and Johnson & Johnson, Nikkiso Europe GMBH and Theravance. LP-B has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis and Theravance., (© The Author(s), 2022.)

Sucrose is effective in reducing pain during minor procedures in neonates. We evaluated whether a second dose of sucrose was more effective than a single dose during venipuncture. We performed a randomised, double-blind, controlled trial at the NICU of Padua Hospital (August 2016-October 2017). We randomised 72 preterm infants undergoing venipuncture for routine test to a control group, which received a single standard dose of sucrose 2' before the procedure and a placebo 30″ after the venipuncture, and an experimental group in which they received two doses of 24% sucrose 2' before and 30″ after the venipuncture. No difference in pain perception was found between the groups at 30″, 60″ and 120″. In conclusion, we do not recommend a second dose of sucrose during venipuncture in prematures., 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., (Copyright © 2022 Cavicchiolo, Daverio, Battajon, Frigo and Lago.)

Introduction: Inflammatory bowel disease (IBD) affects people from all age categories worldwide. Although the incidence of the disease is stabilizing or decreasing in most Western world countries, its prevalence is still increasing because of the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD incidence nationwide, analyzing regional, sex, and age distributions., Methods: Data were provided by the Portuguese Shared Services of the Ministry of Health. This study consisted of a retrospective analysis of all first consultations coded for "Chronic enteritis/ulcerative colitis" (D94) in a primary healthcare setting, between 2017 and 2020, in Portugal. The primary outcome measure was the IBD incidence rate per 100,000 inhabitants. We also calculated the incidence rate per person-year and forecasted incidence until 2024., Results: Between 2017 and 2019, the incidence rate of IBD in Portugal decreased from 54.9 to 48.6 per 100,000 inhabitants. The average incidence was 20 new cases of IBD per 1,000 person-year. It was predicted that, in December 2023, IBD incidence would reach 305.4 new cases (95% Prediction Interval 156.6-454.3), a similar result to the values forecasted for December 2021 (305.4, 95% Prediction Interval 197.3-413.6)., Discussion: The incidence of IBD slightly declined from 2017 to 2019, and it is posed to stabilize in the future. The presented data are of the utmost importance for the characterization of IBD in Southern European countries and the establishment of future health policies in the setting of compounding prevalence in the Western world., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Architectural Technical Debt (ATD) in a software-intensive system denotes architectural design choices which, while being suitable or even optimal when adopted, lower the maintainability and evolvability of the system in the long term, hindering future development activities. Despite the growing research interest in ATD, how to gain an informative and encompassing viewpoint of the ATD present in a software-intensive system is still an open problem., Objective: In this study, we evaluate ATDx, a data-driven approach providing an overview of the ATD present in a software-intensive system. The approach, based on the analysis of a software portfolio, calculates severity levels of architectural rule violations via a clustering algorithm, and aggregates results into different ATD dimensions., Method: To evaluate ATDx, we implement an instance of the approach based on SonarQube, and run the analysis on the Apache and ONAP ecosystems. The analysis results are then shared with the portfolio contributors, who are invited to participate in an online survey designed to evaluate the representativeness and actionability of the approach., Results: The survey results confirm the representativeness of the ATDx, in terms of both the ATDx analysis results and the used architectural technical debt dimensions. Results also showed the actionability of the approach, although to a lower extent when compared to the ATDx representativeness, with usage scenarios including refactoring, code review, communication, and ATD evolution analysis., Conclusions: With ATDx, we strive for the establishment of a sound, comprehensive, and intuitive architectural view of the ATD identifiable via source code analysis. The collected results are promising, and display both the representativeness and actionability of the approach. As future work, we plan to consolidate the approach via further empirical experimentation, by considering other development contexts ( e.g., proprietary portfolios and other source code analysis tools), and enhancing the ATDx report capabilities., Competing Interests: The authors declare there are no competing interests., (©2022 Verdecchia et al.)

Background: Suspected early-onset sepsis (EOS) results in antibiotic treatment and blood withdraw of a substantial number of neonates who are uninfected. We evaluated if the EOS calculator can reduce antibiotic exposure and invasive procedures for suspected EOS in term and late preterm neonates, without any significant increase in adverse outcomes., Methods: The proportion of EOS risk in neonates ≥35 weeks gestation exposed to antibiotics, intensive monitoring and blood withdrawal was compared between a baseline period (January 2018-May 2018), when Centers for Disease Control guidelines approach was used, and a post-EOS calculator-implementation period (June 2018-December 2019)., Results: We included 4363 newborn infants with gestational age ≥35 weeks, respectively 824 in baseline period and 3539 in the EOS calculator period. Among them, 1021 (23.4%) infants presented risk factors for neonatal sepsis. There was a halving in empirical antibiotics exposure: 3% in the baseline and 1.4% in the post-EOS-implementation period, P < 0.05. Blood culture and laboratory evaluations had fallen from 30.6% to 15.4% (P < 0.05). Close monitoring of vital parameters decreased from 25.4% to 4.8% (P < 0.05). The number of antibiotic days per 100 live births decreased from 15.05 to 6.36 days (P <0.05). The incidence of culture-confirmed sepsis and clinical sepsis was very low in 2 periods. Only one infant identified at low-risk by Kaiser calculator at birth developed symptoms after 12 h from birth. We had no readmissions for EOS., Conclusions: Application of the EOS calculator more than halved the burden of intensive monitoring and antibiotic exposure, without compromising safety in a population with a relatively low incidence of culture-proven EOS and good access to follow-up care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes., Objective: This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes., Methods: A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest., Results: A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased., Conclusion: The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background & Aims: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid., Methods: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs., Results: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 μg/g., Conclusions: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Oral sucrose is included in almost all recommendations for treatment of pain in newborns, but evidence if multiple doses might be more effective than a single standard dose is lacking. We designed a single-centre, double-blind, randomised, controlled trial. We enrolled preterm infants needing the heel prick procedure. Each enrolled infant was randomised to receive a single standard dose of sucrose 2 min before or a double dose of sucrose 2 min before, and 30 s after heel prick. Primary outcome was the efficacy of the two interventions tested by the premature infant pain profile-PIPP scale obtained at 30 s, 60 s, and 120 s after heel prick. Secondary outcome was the evaluation of the concordance between the PIPP scale and other pain scores more feasible in clinical practice. Seventy-two infants were randomised. No difference in pain perception as measured by the PIPP scale was found between the groups: median PIPP values 4.0(IQR 3.0-4.0) vs 3.0(IQR 3.0-4.0) at baseline; 6.0(IQR 5.0-10.0) vs 6.0(IQR 4.0-8.5) at 30 s; 6.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-8.5) at 60 s and 5.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-7.5) at 2 min, in the experimental and standard treatment groups, respectively (p = 0.9020). There was no correlation between PIPP scores and other pain scales.Conclusion: We do not recommend doubling the dose during heel prick.What is Known:• Oral sucrose is included in almost all international position papers and recommendations for the treatment of mild to moderate pain in newborns, associated with non-nutritive sucking and facilitated tucking• Premature infant pain profile (PIPP) scale is the gold standard for evaluation of pain in preterms but it is difficult to use in clinical practiceWhat is New:• Repeating a dose of 24% sucrose is not effective in reducing pain during the recovery phase of a skin breaking procedure• Other pain scales, easier to use in clinical practice, are not comparable with PIPP for the evaluation of procedural pain in preterms.

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.

Background and Aim: Aeromonas are Gram-negative rods known to cause a spectrum of diseases. Inflammatory bowel disease (IBD) is an idiopathic complex condition resulting from interaction of multiple factors. Aeromonas infection in association with IBD is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients., Methods: A retrospective observational analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a tertiary and university hospital., Results: Fifty patients were included, 56% male with a mean age of 42.1 years. Thirty-eight (76%) were non-IBD and 12 (24%) IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% developed mild, 44% moderate, and 16.7% severe infection. The main strains isolated were Aeromonas hydrophila/caviae . Bacterial co-isolation was found in 4 non-IBD and histological findings of cytomegalovirus in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in the IBD group. From IBD, 4 patients had the diagnosis of ulcerative colitis and 9 of Crohn's disease with colonic involvement. Of these patients, 5 received IBD diagnosis after the acute episode of Aeromonas infection., Conclusions: Clinical presentation of Aeromonas infection differs between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seems to greatly contribute to IBD manifestation., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by Sociedade Portuguesa de Gastrenterologia Published by S. Karger AG, Basel.)

Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9 , or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.

The aim of this study was to describe the epidemiological characteristics and clinical outcome of children hospitalized with COVID-19 and identify the risk factors for severe disease. All hospital admissions of pediatric patients between March and December 2020 in the southern region of Brazil were reviewed and the patients positive for RT-PCR for SARS-CoV-2 were identified. This region encompasses a population of over 2.8 million children and adolescents. Data were extracted from a national database that includes all cases of severe acute respiratory syndrome requiring hospitalization in Brazil. A total of 288 hospitalizations (51.3% female) with a median age of 3 years (interquartile range 0-12 years) were identified. Of these, 38.9% had chronic medical conditions, 55.6% required some form of supplementary oxygen, and 30.2% were admitted to an intensive care unit. There were 17 deaths (5.9%) related to COVID-19. Age less than 30 days was significantly associated with increased odds of critical illness (OR 9.52, 95% CI 3.01-30.08), as well as the presence of one chronic condition (OR 5.08 95%CI 2.78-9.33) or two or more chronic conditions (OR 6.60, 95% CI 3.17-13.74). Conclusion: Age under 30 days old and presence of chronic conditions were strongly associated with unfavorable outcomes in Brazilian children with SARS-CoV-2 infection. These findings could help local public health authorities to develop specific policies to protect this more vulnerable group of children., Competing Interests: Conflicts of interest The authors declare no conflicts of interests., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF., Methods: Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with β-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received β-alanine and L-histidine orally (250 mg/kg per day)., Results: Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED., Conclusion: CET together with β-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: In vitro diagnostic tests for SARS-COV-2, also known as serological tests, have rapidly spread. However, to date, mostly single-center technical and diagnostic performance's assessments have been carried out without an intralaboratory validation process and a health technology assessment (HTA) systematic approach. Therefore, the rapid HTA for evaluating antibody tests for SARS-COV-2 was applied., Methods: The use of rapid HTA is an opportunity to test innovative technology. Unlike traditional HTA (which evaluates the benefits of new technologies after being tested in clinical trials or have been applied in practice for some time), the rapid HTA is performed during the early stages of developing new technology. A multidisciplinary team conducted the rapid HTA following the HTA Core Model® (version 3.0) developed by the European Network for Health Technology Assessment., Results: The three methodological and analytical steps used in the HTA applied to the evaluation of antibody tests for SARS-COV-2 are reported: the selection of the tests to be evaluated; the research and collection of information to support the adoption and appropriateness of the technology; and the preparation of the final reports and their dissemination. Finally, the rapid HTA of serological tests for SARS-CoV-2 is summarized in a report that allows its dissemination and communication., Conclusions: The rapid-HTA evaluation method, in addition to highlighting the characteristics that differentiate the tests from each other, guarantees a timely and appropriate evaluation, becoming a tool to create a direct link between science and health management.

The Covid-19 European outbreak in February 2020 has challenged the world's health systems, eliciting an urgent need for effective and highly reliable diagnostic instruments to help medical personnel. Deep learning (DL) has been demonstrated to be useful for diagnosis using both computed tomography (CT) scans and chest X-rays (CXR), whereby the former typically yields more accurate results. However, the pivoting function of a CT scan during the pandemic presents several drawbacks, including high cost and cross-contamination problems. Radiation-free lung ultrasound (LUS) imaging, which requires high expertise and is thus being underutilised, has demonstrated a strong correlation with CT scan results and a high reliability in pneumonia detection even in the early stages. In this study, we developed a system based on modern DL methodologies in close collaboration with Fondazione IRCCS Policlinico San Matteo's Emergency Department (ED) of Pavia. Using a reliable dataset comprising ultrasound clips originating from linear and convex probes in 2908 frames from 450 hospitalised patients, we conducted an investigation into detecting Covid-19 patterns and ranking them considering two severity scales. This study differs from other research projects by its novel approach involving four and seven classes. Patients admitted to the ED underwent 12 LUS examinations in different chest parts, each evaluated according to standardised severity scales. We adopted residual convolutional neural networks (CNNs), transfer learning, and data augmentation techniques. Hence, employing methodological hyperparameter tuning, we produced state-of-the-art results meeting F1 score levels, averaged over the number of classes considered, exceeding 98%, and thereby manifesting stable measurements over precision and recall., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Ensure access to perinatal palliative care (PnPC) to all eligible fetuses/infants/parents., Design: During 12 meetings in 2016, a multidisciplinary work-group (WG) performed literature review (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method was applied), including the ethical and legal references, in order to propose shared care pathway., Setting: Maternal-Infant Department of Padua's University Hospital., Patients: PnPC eligible population has been divided into three main groups: extremely preterm newborns (first group), newborns with prenatal/postnatal diagnosis of life-limiting and/or life-threatening disease and poor prognosis (second group) and newborns for whom a shift to PnPC is appropriate after the initial intensive care (third group)., Interventions: The multidisciplinary WG has shared care pathway for these three groups and defined roles and responsibilities., Main Outcome Measures: Prenatal and postnatal management, symptom's treatment, end-of-life care., Results: The best care setting and the best practice for PnPC have been defined, as well as the indications for family support, corpse management and postmortem counselling, as well suggestion for conflicts' mediation., Conclusions: PnPC represents an emerging field within the paediatric palliative care and calls for the development of dedicated shared pathways, in order to ensure accessibility and quality of care to this specific population of newborns., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)