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BACKGROUND: Prematurity is the strongest predictor of bronchopulmonary dysplasia (BPD). Most previous studies investigated additional risk factors by conventional statistics, while the few studies applying artificial intelligence, and specifically machine learning (ML), for this purpose were mainly targeted to the predictive ability of specific interventions. This study aimed to apply ML to identify, among routinely collected data, variables predictive of BPD, and to compare these variables with those identified through conventional statistics. METHODS: Very preterm infants were recruited; antenatal, perinatal, and postnatal clinical data were collected. A BPD prediction model was built using conventional statistics, and nine supervised ML algorithms were applied for the same purpose: the results of the best-performing model were described and compared with those of conventional statistics. RESULTS: Both conventional statistics and ML identified the degree of immaturity (low gestational age and/or birth weight), need for mechanical ventilation, and absent or reversed end diastolic flow (AREDF) in the umbilical arteries as risk factors for BPD. Each of the two approaches also identified additional potentially predictive clinical variables. CONCLUSION: ML algorithms might be useful to integrate conventional statistics in identifying novel risk factors, in addition to prematurity, for the development of BPD in very preterm infants. Specifically, the identification of AREDF status as an independent risk factor for BPD by both conventional statistics and ML highlights the opportunity to include detailed antenatal information in clinical predictive models for neonatal diseases.
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Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care.
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BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.
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BACKGROUND AND AIM: Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. METHODS: Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. RESULTS: Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. CONCLUSIONS: Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. IMPACT: This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.
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Purpose: The objective of this research was to develop a musical digital game for rehabilitation of upper limb and to verify its usability and user experience with professionals in the field (physical therapists). Materials and Methods: Thirty working professionals were recruited to evaluate the system. The usability was evaluated with the System Usability Scale (SUS) and the user experience was verified with the Game Flow scale. Results: The overall score of the SUS scale was 88.67 (±9.129); this score is interpreted as "Best Imaginable" (86-100). The user experience rating had most of its domains equal or higher than 4, which indicates that all the requirements for a good user experience were present in the game. Conclusions: The Moniz Game proved to be a game with good usability and can be a tool for application in clinical practice regarding motor coordination. However, further studies are needed to evaluate the effect of the Moniz Game on motor coordination in patients with neurological dysfunctions.
Subject(s)
Music , Video Games , Humans , Video Games/psychology , Video Games/standards , Video Games/statistics & numerical data , Adult , Female , Male , Music/psychology , User-Computer Interface , Upper Extremity/physiology , Middle Aged , Motor Skills/physiologyABSTRACT
BACKGROUND: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population. RESULTS: Thirty-one individuals were enrolled (17 females/14 males; age range 0.1-17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14. CONCLUSIONS: Brain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.
Subject(s)
Brain Diseases , Chromosome Disorders , Polymicrogyria , Male , Female , Humans , Child , Infant , Child, Preschool , Adolescent , Chromosome Disorders/diagnostic imaging , Chromosome Disorders/genetics , Neuroimaging , Brain/diagnostic imaging , Chromosomes, Human, Pair 12 , Observational Studies as TopicABSTRACT
BACKGROUND: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS: In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS: From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS: Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.
Subject(s)
Cholangitis, Sclerosing , Liver Transplantation , Waiting Lists , Humans , Cholangitis, Sclerosing/surgery , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/mortality , Male , Female , Middle Aged , Italy/epidemiology , Adult , Waiting Lists/mortality , Recurrence , Aged , Cholangiocarcinoma/surgeryABSTRACT
BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.
Subject(s)
Acute Kidney Injury , Contrast Media , Humans , Lipocalin-2 , Cohort Studies , Contrast Media/adverse effects , Retrospective Studies , Prospective Studies , Liver Cirrhosis/complications , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , BiomarkersABSTRACT
BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.
Subject(s)
Bronchopulmonary Dysplasia , Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Humans , Infant, Newborn , Bronchopulmonary Dysplasia/prevention & control , Continuous Positive Airway Pressure/adverse effects , Infant, Premature , Lung/diagnostic imaging , Oxygen/therapeutic use , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/therapy , Surface-Active Agents/therapeutic use , Ultrasonography, InterventionalABSTRACT
Extracellular vesicles (EVs) are emerging as a promising field of research in liver disease. EVs are small, membrane-bound vesicles that contain various bioactive molecules, such as proteins, lipids, and nucleic acids and are involved in intercellular communication. They have been implicated in numerous physiological and pathological processes, including immune modulation and tissue repair, which make their use appealing in liver transplantation (LT). This review summarizes the current state of knowledge regarding the role of EVs in LT, including their potential use as biomarkers and therapeutic agents and their role in graft rejection. By providing a comprehensive insight into this emerging topic, this research lays the groundwork for the potential application of EVs in LT.
Subject(s)
Extracellular Vesicles , Liver Transplantation , Nucleic Acids , Cell Communication , Graft RejectionABSTRACT
BACKGROUND: Since November 2020, Italy was the first country to carry out a protocol and use liver from COVID-19 donors. We aimed to evaluate the medium-term outcome of patients who underwent liver transplant (LT) with those grafts. METHODS: We consecutively enrolled 283 patients who underwent first LT from November 2020 to December 2022 in our Center (follow-up 468 days). Twenty-five of 283 (8.8%, study population) received a graft from donors with previous (4%) or active (96%) SARS-CoV-2 infection, and 258/283 (91.2%, control group) received a graft from COVID-19-negative donors. SARS-CoV-2-RNA was tested on graft tissue of COVID-19 donors and their recipients underwent weekly evaluation of SARS-CoV-2-RNA in nasal swabs for the first month after LT. RESULTS: One-year and 2-year patient survival was 88.5% and 88.5% in study group versus 94.5% and 93.5% in control group, respectively (p = .531). In study population there was no evidence of donor-recipient virus transmission, but three (12%) patients (vs. 7 [2.7%] of control group, p = .048) developed hepatic artery thrombosis (HAT): they were SARS-CoV-2-RNA negative at LT and 1/3 grafts tested SARS-CoV-2-RNA positive on liver tissue. COVID-19 donor was independently associated with HAT (odds ratio (OR) = 4.85, 95% confidence interval (CI) 1.10-19.15; p = .037). By comparing study population with control group, acute rejection and biliary complication rates were not significantly different (16% vs. 8.1%, p = .26; 16% vs. 16.3% p = .99, respectively). CONCLUSIONS: Our 1-year results of transplant strategy including liver grafts from COVID-19 donors were favorable. HAT was the only complication with significantly higher rate in patients transplanted with COVID-19 donors compared with control group.
Subject(s)
COVID-19 , Humans , Follow-Up Studies , SARS-CoV-2 , Liver , Tissue Donors , RNA , Graft SurvivalABSTRACT
Introduction: The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Methods: Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Results: Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. Discussion: According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.
Subject(s)
COVID-19 , Organ Transplantation , Humans , COVID-19/epidemiology , SARS-CoV-2 , Liver , Organ Transplantation/adverse effects , Italy/epidemiologyABSTRACT
This prospective observational study aimed to evaluate whether lung fluids, assessed by lung ultrasonography and transthoracic electrical bioimpedance (TEB), may be influenced by the presence of a haemodynamically significant patent ductus arteriosus (hsPDA) in very preterm infants during the transitional period. Infants < 32 weeks of gestational age (GA) admitted to the neonatal intensive care units of IRCCS AOU Bologna and Niguarda Metropolitan Hospital of Milan (Italy) underwent a daily assessment of a lung ultrasound score (LUS) and of a TEB-derived index of thoracic fluid contents (TFC) during the first 72 h after birth. Echocardiographic scans were simultaneously performed to evaluate the concomitant ductal status (hsPDA vs. restrictive or closed duct). The correlation between LUS, TFC, and the ductal status was tested using generalized estimating equations. Forty-six infants (median GA: 29 [interquartile range, IQR: 27-31] weeks; median birth weight: 1099 [IQR: 880-1406] g) were included. At each daily evaluation, the presence of a hsPDA was associated with significantly higher LUS and TFC compared with a restrictive or closed ductus (p < 0.01 for all comparisons). These results were confirmed significant even after adjustment for GA and for the ongoing modality of respiratory support. Conclusion: Even during the first 72 h of life, the presence of a hsPDA determines a significant increase in pulmonary fluids which can be non-invasively detected and monitored over time using lung ultrasonography and TEB. What is Known: ⢠Lung ultrasonography provides a non-invasive assessment of lung fluids and is widely used in neonatal settings. ⢠In preterm infants, the persistence of a haemodynamically significant patent ductus arteriosus (hsPDA) over the first weeks can negatively affect pulmonary outcomes. What is New: ⢠The presence of aan hsPDA is associated with increased lung fluids since early postnatal phases. ⢠Lung ultrasonography and transthoracic electrical bioimpedance can effectively monitor lung fluid clearance in preterm infants with a hsPDA during the transitional period, with potential clinical implications.
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OBJECTIVE: To evaluate the relationship between impaired brain growth and structural brain abnormalities at term-equivalent age (TEA) and neurodevelopment in extremely low-birth-weight (ELBW) infants over the first 2 years. METHODS: ELBW infants born from 2009 through 2018 and undergoing brain magnetic resonance imaging (MRI) at TEA were enrolled in this retrospective cohort study. MRI scans were reviewed using a validated quali-quantitative score, including several white and gray matter items. Neurodevelopment was assessed at 6, 12, 18, and 24 months using the Griffiths scales. The independent associations between MRI subscores and the trajectories of general and specific neurodevelopmental functions were analyzed by generalized estimating equations. RESULTS: One hundred-nine ELBW infants were included. White matter volume reduction and delayed myelination were associated with worse general development (b = -2.33, P = .040; b = -6.88, P = .049 respectively), social skills (b = -3.13, P = .019; b = -4.79, P = .049), and eye-hand coordination (b = -3.48, P = .009; b = -7.21, P = .045). Cystic white matter lesions were associated with poorer motor outcomes (b = -4.99, P = .027), while white matter signal abnormalities and corpus callosum thinning were associated with worse nonverbal cognitive performances (b = -6.42, P = .010; b = -6.72, P = .021, respectively). Deep gray matter volume reduction correlated with worse developmental trajectories. CONCLUSIONS: Distinctive MRI abnormalities correlate with specific later developmental skills. This finding may suggest that TEA brain MRI may assist with neurodevelopmental prediction, counseling of families, and development of targeted supportive interventions to improve neurodevelopment in ELBW neonates.
Subject(s)
Brain Diseases , Infant, Premature , Infant, Newborn , Infant , Humans , Child, Preschool , Retrospective Studies , Magnetic Resonance Imaging/methods , Brain/pathology , Infant, Extremely Low Birth WeightABSTRACT
This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain. Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors. What is Known: ⢠Foetal growth restriction (FGR), together with antenatal umbilical Doppler abnormalities, is known to affect maternal and neonatal outcomes. ⢠Infants born preterm and growth-restricted face the highest risk for neurodevelopmental impairment, especially when FGR occurs early during pregnancy (early FGR, before 32 weeks gestation). What is New: ⢠The timing of onset and features of FGR and antenatal umbilical Doppler abnormalities impact differently on maternal and neonatal outcomes; when FGR and Doppler abnormalities occur very early, at the limit of neonatal viability, and persist until delivery, infants face the highest risk for neurodevelopmental impairment. ⢠Shared knowledge between obstetricians and neonatologists about timing of onset and features of FGR would provide a valuable tool for informed antenatal counselling in high-risk pregnancies.
Subject(s)
Fetal Growth Retardation , Infant, Premature , Infant , Pregnancy , Female , Infant, Newborn , Humans , Fetal Growth Retardation/diagnosis , Cohort Studies , Retrospective Studies , Umbilical Arteries/diagnostic imaging , Gestational Age , Ultrasonography, PrenatalABSTRACT
The objectives of this study were to develop and validate a computerized device to measure joint flexibility; to measure flexibility in children in elementary school aged 8 to 10 years using the Wells bank; to compare the data obtained by the Wells bank and the computerized device developed in the present study and evaluate the usability of the device. 215 volunteers participated in this research, aged between 8 and 10 years, 63.72% (137) were female and 36.28% (78) were male, duly enrolled in an educational institution in the Alto Tietê region. For data collection, the volunteers performed the flexibility test using the Wells bank and the computerized device developed in this research to assess flexibility. The computerized device it was made on a 3D printing technology printer. A usability evaluation was carried out with 15 Physical Education teachers for the product developed through a usability questionnaire based on the System Usability Scale (SUS) form, which contains 10 multiple-choice questions. The data obtained by the objective measures determined were evaluated in terms of frequency, mean and standard deviation. The arithmetic means of the three measurements performed at each stage were calculated. Mann-Whitney and Kruskal-Wallis tests and Spearman's correlation were performed for the investigation. For all analyses, significant differences were considered p<0.05. It is concluded that the computerized device to measure joint flexibility is capable of evaluating the range of motion in degrees, and was qualified as easy to handle by professionals in the field of physical education.
Los objetivos de este estudio fueron desarrollar y validar un dispositivo computarizado para medir la flexibilidad articular; medir la flexibilidad en niños en la escuela primaria de 8 a 10 años a través del banco Wells; comparar los datos obtenidos por la base de datos Wells y el dispositivo computarizado desarrollado en el presente estudio y evaluar la usabilidad del dispositivo. Un total de 215 voluntarios participaron en esta investigación, con edades de 8 a 10 años, 63,72% (137) mujeres y 36,28% (78) hombres, debidamente matriculados en una institución educativa de la región del Alto Tietê. Para la recolección de datos, los voluntarios realizaron la prueba de flexibilidad utilizando la base de datos Wells y el dispositivo computarizado desarrollado en esta investigación para evaluar la flexibilidad. El dispositivo fue hecho de una impresora de tecnología de impresión 3D. Se realizó una evaluación de usabilidad con 15 profesores de Educación Física para el producto desarrollado a través del cuestionario de usabilidad basado en el formulario System Usability Scale (SUS) que contiene 10 preguntas de opción múltiple. Los datos obtenidos por las mediciones objetivas determinadas fueron evaluados para la frecuencia, media y desviación estándar. Se calcularon las medias aritméticas de las tres mediciones realizadas en cada etapa. Las pruebas de Mann-Whitney y Kruskal-Wallis y la correlación de Spearman se realizaron para la investigación. Para todos los análisis, se consideraron diferencias significativas p<0,05. Se concluye que el dispositivo computarizado para medir la flexibilidad articular es capaz de evaluar el rango de movimiento en grados, y fue calificado fácil de manejar por profesionales de la educación física.
Os objetivos deste estudo foram desenvolver e validar um dispositivo computadorizado para mensurar a flexibilidade articular; mensurar a flexibilidade em crianças no ensino fundamental de 8 a 10 anos por meio do banco de Wells; comparar os dados alcançados pelo banco de Wells e o dispositivo computadorizado desenvolvido no presente estudo e avaliar a usabilidade do dispositivo. Participaram desta pesquisa 215 voluntários, com idade de 8 a 10 anos, sendo 63,72% (137) do sexo feminino e 36,28% (78) do sexo masculino, devidamente matriculados em uma instituição de ensino na região do Alto Tietê. Para coleta de dados, os voluntários realizaram o teste de flexibilidade utilizando o banco de Wells e o dispositivo computadorizado desenvolvido nessa pesquisa para avaliar a flexibilidade.O dispositivo foi confeccionado numa impressora de tecnologia de impressão 3D. Foi realizada uma avaliação da usabilidade com 15 professores de Educação Física para o produto desenvolvido através da interação de usabilidade baseada no formulário System Sustainability Scale (SUS) que contém 10 questões de múltipla-escolha. Os dados obtidos por medidas objetivas determinadas foram avaliadas quanto à frequência, média e desvio padrão. Foram seguidas como médias aritméticas das três medidas realizadas em cada etapa. Para investigar realizou-se os testes de Mann-Whitney e de Kruskal-Wallis e a tradução de Spearman. Para todas as análises foram consideradas diferenças significativas p<0,05.Conclui-se que o dispositivo computadorizado para medir a flexibilidade articular é capaz de avaliar em graus a amplitude de movimento,
ABSTRACT
Despite the significant outcomes attained by scientific research, breast cancer (BC) still represents the second leading cause of death in women. Estrogen receptor-positive (ER+) BC accounts for the majority of diagnosed BCs, highlighting the disruption of estrogenic signalling as target for first-line treatment. This goal is presently pursued by inhibiting aromatase (AR) enzyme or by modulating Estrogen Receptor (ER) α. An appealing strategy for fighting BC and reducing side effects and resistance issues may lie in the design of multifunctional compounds able to simultaneously target AR and ER. In this paper, previously reported flavonoid-related potent AR inhibitors were suitably modified with the aim of also targeting ERα. As a result, homoisoflavone derivatives 3b and 4a emerged as well-balanced submicromolar dual acting compounds. An extensive computational study was then performed to gain insights into the interactions the best compounds established with the two targets. This study highlighted the feasibility of switching from single-target compounds to balanced dual-acting agents, confirming that a multi-target approach may represent a valid therapeutic option to counteract ER+ BC. The homoisoflavone core emerged as a valuable natural-inspired scaffold for the design of multifunctional compounds.